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Acute-on-chronic liver failure has complex conditions， rapid progression， and a high mortality rate， and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure， but also provide an experimental basis for clinical treatment. Through a literature review， this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure， including carbon tetrachloride combined with LPS/GaIN， thioacetamide combined with LPS， serum albumin， and bile duct ligation. This article analyzes the characteristics of various animal models， so as to provide documentary and experimental bases for further exploration of more ideal animal models. [ABSTRACT FROM AUTHOR]

Objective The construction of animal models of neonatal necrotizing enterocolitis (NEC) is still not uniform, and animal modeling approaches that are more relevant to the actual clinical situation of NEC childern should be clarified. Methods Fifly-four newborn mice were randomized into five groups of control (Ctrl), hypoxia plus artificial feeding (HF), hypoxia plus artificial feeding plus cold stimulation (Cold), hypoxia plus artificial feeding plus lipopolysaccharide (LPS) and hypoxia plus artificial feeding plus intestinal bacteria in NEC (Bac).After successful modeling, intestinal pathology, NEC-related intestinal epithelial barrier proteins (β-catenin & Occludin), intestinal epithelial cell death (CC3, RIPK1 & PARP1) and pro-inflammatory cytokines (IL-6, TNF-α & MCP1) were evaluated. Results Nadler score ≥2 according to intestinal histology was considered as NEC-like intestinal injury. In this study, the intestinal histopathology of the three NEC-modeled groups met the criteria for NEC-like intestinal injury, except for the Ctrl and HF groups. Compared with the NEC modeling groups HF (30%), Cold (83.3%) and LPS (81.8%), the Bac group had the highest modeling success rate (100%), and the mental status, bloating and diarrhea, and mobility of the mice in the Bac group during the modeling period were more consistent with clinical NEC. Meanwhile, the expression of intestinal barrier proteins β-catenin and Occludin was decreased in the Bac group mice, and the difference was statistically significant compared with the Ctrl group (P < 0.05). the expression of intestinal epithelial cell death marker molecules RIPK1 and PARP1 was upregulated in the LPS and Bac groups, and the expression levels of inflammatory factors IL-6, TNF-α and MCP1 were increased compared with the Ctrl group, with statistically significant differences (P < 0.05). Conclusion This study has successfully established four NEC animal models and verified a more appropriate animal modeling method of clinical NEC, namely "hypoxia plus artificial feeding plus NEC intestinal bacteria".Such a modeling method has a high success rate.And intestinal histopathological injury, intestinal barrier protein expression and systemic inflammatory response mimic closely the clinical characteristics of NEC. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of vascular endothelial growth factor (VEGF) and the Wnt/β-catenin signaling pathway in gingival tissues remodeling by measuring the changes in VEGF and β-catenin expression in mouse gingival tissues under hyperocclusion. Methods Thirty male Kunming mice aged four weeks were randomly divided into control group (n=15) and experimental group (n=15). All the right maxillary molars of mice in the experimental group were extracted to establish a hyperocclusion model. On the 3rd, 7th, 14th, 28th, and 56th days after operation, three mice in each group were randomly selected and sacrificed under anesthesia. Their left mandibular first molars with the gingival tissues were isolated. Hematoxylin-eosin (HE) staining was performed to observe the histological changes of the gingiva, and immunohistochemical staining was used to measure the changes in VEGF and β-catenin expression in the gingival tissues. Results The HE staining showed that in the experimental group, the thickness of gingival tissues and the number of blood vessels increased on day 14 after tooth extraction. The results of immunohistochemical examination showed that in the control group, there were no significant differences in the expression of VEGF and β-catenin in the gingival tissues between different time points (P>0.05); while in the experimental group, there were significant differences in that between different time points (F=250.4,343.9,P

Background The use of electroacupuncture at Shenting and Baihui acupoints may improve the learning and memory impairment in cerebral ischemic stroke patients with cognitive impairment induced by one pathogenic factor known as abnormal free radical metabolism. Objective To explore the possible mechanism of using electroacupuncture at Shenting and Baihui acupoints to improve the learning and memory impairment in a rat model of cerebral ischemia-reperfusion induced learning and memory impairment by observing the changes of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in brain tissues of the model. Methods This experiment was conducted from August 2019 to August 2020. Eighteen SPF male SD rats were selected and equally randomized into three groups by use of random allocation using SPSS 22.0: sham operation group (receiving a neck incision for separating the neck artery, then being caught at a fixed time point), model group (receiving occlusion of the middle cerebral artery for inducing ischemia-reperfusion injury, then being assessed with a Zea-Longa score of 1-3 points in the fully awake state, and being caught at a fixed time point) and electroacupuncture group (first receiving interventions similar to those given to rats in the model group, then on the first day after being successfully modeled, receiving a 30-minute electroacupuncture at Shenting and Baihui acupoints with dense-sparse waves in the frequency range of 1 Hz/20 Hz, once daily, for two consecutive weeks). When the intervention ended, Morris water maze experiment was used to test the learning and memory ability of all rats. The SOD activity and MDA content in brain tissues of rats were measured by WST-1 assay, and thiobarbituric acid assay, respectively. Results The rats in both model group and electroacupuncture group were modeled successfully. On the 13th day of training trial, compared with rats in the sham operation group, those in the model group showed an increased escape latency and decreased number of crossing the platform (P

Objective To study the effect of overwork stress response on the expression of connexin 43（Cx43） and connexin 45（Cx45） in cardiomyocytes and on cardiac function. Methods The experimental animals were divided into control group, overworked 1-month group and overworked 2-month group. A overworked rat model was established by forcing swimming of overworked group. The expressions of Cx43 and Cx45 in myocardial tissues of experimental animals were detected by Western blotting, while the corresponding myocardial tissues were stained with hematoxylin-eosin （HE） staining and Masson’s staining, then histologically observed. Results Western blotting results showed that, compared with the control group, Cx43 expression in myocardial tissues of overworked rats decreased while Cx45 expression increased. HE staining and Masson’s staining results showed that hypertrophy, rupture and interstitial fiber tissue hyperplasia were observed in myocardial fibers of overworked rats. Conclusion Overwork stress response may affect cardiac function as an independent factor and may even cause heart failure or arrhythmias and lead to death.

Parkinson's disease (PD) is the second most common neurodegenerative disease. A number of studies have shown that α -synuclein (α -syn) is closely related to the pathogenesis of Parkinson's disease. Domestic and foreign researchers have established PD animal models via the ectopic expression, overexpression or intracerebral injection of α- syn. In recent years, α-synuclein preformed fibrils (α-syn PFFs) have been used in the construction of animal models. α-syn PFFs play an important role in the study of the origin of PD and the transmission of neuronal degeneration. Compared with the toxin-induced models, these models can better reproduce the characteristics of pathological changes of PD patients. In this article, we mainly reviewed the research progress in α-synuclein-based animal models of PD. [ABSTRACT FROM AUTHOR]

Objective: Female fertility gradually decreases with the increase in women's age. The underlying reasons include the decline in the quantity and quality of oocytes. Oocyte aging is an important manifestation of the decline in oocyte quality, including in vivo oocyte aging before ovulation and in vitro oocyte aging after ovulation. Currently, few studies have been done to examine oocyte aging, and the relevant molecular mechanisms are not fully understood. Therefore, we used zebrafish as a model to investigate oocyte aging. Three different age ranges of female zebrafish were selected to mate with male zebrafish of the best breeding age. In this way, we studied the effects of maternal age-related oocyte aging on fertility and investigated the potential molecular mechanisms behind maternal age-related fertility decline., Methods: Eight female zebrafish aged between 158 and 195 d were randomly selected for the 6-month age group (180±12) d, 8 female zebrafish aged between 330 and 395 d were randomly selected for the 12-month age group (360±22) d, and 8 female zebrafish aged between 502 and 583 d were randomly selected for the 18-month age group (540±26) d. Male zebrafish of (180±29) d were randomly selected from zebrafish aged between 158 and 195 d and mated with female zebrafish in each group. Each mating experiment included 1 female zebrafish and 1 male zebrafish. Zebrafish embryos produced by the mating experiments were collected and counted. The embryos at 4 hours post-fertilization were observed under the microscope, the total number of embryos and the number of unfertilized embryos were counted, and the fertilization rate was calculated accordingly. The numbers of malformed embryos and dead embryos were counted 24 hours after fertilization, and the rates of embryo malformation and mortality were calculated accordingly. The primary outcome measure was the embryo fertilization rate, and the secondary outcome measures were the number of embryos per spawn (the total number of embryos laid within 1.5 hours after the beginning of mating and reproduction of the zebrafish), embryo mortality, and embryo malformation rate. The outcome measures of each group were compared. The blastocyst embryos of female zebrafish from each group born after mating with male zebrafish in their best breeding period were collected for transcriptomics analysis. Fresh oocytes of female zebrafish in each group were collected for transcriptomics analysis to explore the potential molecular mechanisms of maternal age-related fertility decline., Results: Compared with that of the 6-month group (94.9%±3.6%), the embryo fertilization rate of the 12-month group (92.3%±4.2%) showed no significant difference, but that of the 18-month group (86.8%±5.5%) decreased significantly ( P <0.01). In addition, the fertilization rate in the 18-month group was significantly lower than that in the 12-month group ( P <0.05). Compared with that of the 6-month group, the embryo mortality of the female zebrafish in the 12-month group and that in the 18-month group were significantly higher than that in the 6-month group ( P <0.000 1, P <0.001). There was no significant difference in the number of embryos per spawn or in the embryo malformation rate among the three groups. The results of the transcriptomics analysis of blastocyst embryos showed that some genes, including dusp5 , bdnf , ppip5k2 , dgkg , aldh3a2 a, acsl1a , hal , mao , etc, were differentially expressed in the 12-month group or the 18-month group compared with their expression levels in the 6-month group. According to the KEGG enrichment analysis, these differentially expressed genes (DEGs) were significantly enriched in the MAPK signaling pathway, the phosphatidylinositol signaling system, and the fatty acid degradation and histidine metabolism pathway ( P <0.05). The analysis of the expression trends of the genes expressed differentially among the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that the gene expression trends of fancc , fancg , fancb , and telo2 , which were involved in Fanconi anemia pathway, were statistically significant ( P <0.05). In the results of oocyte transcriptomics analysis, the genes that were differentially expressed in the 12-month group or the 18-month group compared with the 6-month group were mainly enriched in cell adhesion molecules and the protein digestion and absorption pathway ( P <0.05). The results of the trends of gene expression in the zebrafish oocytes of the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that three kinds of gene expression trends of declining fertility with growing maternal age had significant differences ( P <0.05). Further analysis of the three significantly differential expression trends showed 51 DEGs related to mitochondria and 5 DEGs related to telomere maintenance and DNA repair, including tomm40 , mpc2 , nbn , tti1 , etc., Conclusion: With the increase in the maternal age of the zebrafish, the embryo fertilization rate decreased significantly and the embryo mortality increased significantly. In addition, with the increase in the maternal age of the zebrafish, the expression of mitochondria and telomere-related genes, such as tomm40 , mpc2 , nbn , and tti1 , in female zebrafish oocytes decreased gradually. Maternal age may be a factor contributing to the decrease in oocyte fertilization ability and the increase in early embryo mortality. Maternal age-related oocyte aging affects the fertility and embryo development of the offspring., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Objective To discuss the damage effect of Solitaire stent on tunica intima during thrombectomy, so as to evaluate the safety of thrombectomy. Methods Twelve healthy male New Zealand rabbits were randomly divided into 4 groups (3 rabbits in each group), including control group and 3 thrombectomy groups. Microcatheter was used instead of stent in control group. The other 3 groups underwent mimic thrombectomy for 1, 3 and 5 times in the same position, respectively. The procedure was performed at both sides of carotid artery of each rabbit. Immediately after operation, bilateral carotid arteries of each rabbit were removed, performed HE staining and examined the ultrastructure under microscope. Semi?quantitative analysis was used to evaluate the damage of carotid artery. Results During the model preparation, DSA showed the diameter of vascular wall was 2.10-2.90 mm, and there was no vascular spasm, bleeding, perforation or arterial dissection. Therefore, the model was successfully established. The difference of carotid artery damage among different groups was statistically significant (F = 119.108, P = 0.000). Compared with control group, the carotid artery damage of 3 thrombectomy groups was more serious (q = 3.136, P = 0.001; q = 7.463, P = 0.000; q = 10.682, P = 0.000). The carotid artery damage of the second and third thrombectomy group was more serious than the first group (q = 3.330, P = 0.000; q = 8.160, P = 0.000). The carotid artery damage of the third thrombectomy group was more serious than the second group (q = 4.830, P = 0.000). Optical microscope observation showed that with the increase of times of thrombectomy, carotid intimal injury was more extensive and intimal reaction was more severe. Scanning electron microscopy showed that with the increase of times of thrombectomy, the degree of carotid artery injury was increased. Conclusions Solitaire stent may injure tunica intima, and with the increase of times of thrombectomy, the damage to vascular wall will increase. DOI: 10.3969/j.issn.1672-6731.2017.11.008

Objectives: The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate, making it difficult to master. This study aims to provide a crucial model for transplantation immunology research by modifying and developing novel techniques for mouse kidney transplantation., Methods: A total of 57 pairs of mice were used to establish and compare the modified and innovative surgical techniques for mouse kidney transplantation. Three different surgical models were established, including the abdominal suture technique for orthotopic kidney transplantation, the abdominal cuff technique for orthotopic kidney transplantation, and the cervical cuff technique for ectopic kidney transplantation. BALB/c or C57BL/6 male mice, aged 8 to 12 weeks and weighed 20 to 25 g with specified pathogen free-grade were served as the donor mice or the recipient mice. The surgical technique characteristics, key surgical times, complications, and pathological examination in the early postoperative period were summarized and compared., Results: Three different surgical models of mouse kidney transplantation were successfully established. The comparison of warm ischemic time for the 3 groups of mice showed no statistical significance ( P =0.510 4). The abdominal suture group had the shortest total operation time of the donor compared with the abdominal cuff group and the cervical cuff group [(18.3±3.6) min vs (26.2±4.7) min and (22.8±2.5) min; both P <0.000 1]. There was a significant difference in cold ischemia time among the 3 groups (all P <0.000 1), with (60.8±4.1) min in the cervical cuff group, (43.3±5.0) min in the abdominal suture group, and (88.8±6.7) min in the abdominal cuff group. Due to different anastomosis methods, the cervical cuff group had the shortest time [(17.6±2.7) min], whereas the abdominal cuff group had the longest time [(38.8±5.4) min]. The total operation time for the recipients showed significant differences ( P <0.000 1), with the abdominal suture group having the shortest time [(44.0±6.9) min], followed by the cervical cuff group [(64.1±5.2) min], and the abdominal cuff group [(80.0±6.0) min] being the longest. In the 32 mice of the abdominal suture group, there were 6 with intraoperative bleeding, including 1 arterial intimal injury bleeding and 5 with bleeding after vessel opening. Six mice had ureteral complications, including ureteral bladder anastomotic stenosis, necrosis, and renal pelvis dilation. Two mice had postoperative abdominal infections. In the abdominal cuff group, there was no intraoperative bleeding, but 6 mice showed mild arterial stenosis and 5 showed venous stenosis, 4 arterial injury, 4 arterial thrombosis, and 2 ureteral complications. No postoperative infections occurred in the mice. In the cervical cuff group, no intraoperative bleeding, arterial intimal injury, arterial/venous stenosis, or thrombosis were found in 13 mice. Five mice had ureteral complications, including ureteral necrosis and infection, which were the main complications in the cervical cuff group. The renal function in mice of the 3 groups remained stable 7 days after surgery. Hematoxylin and eosin staining and periodic acid-Schiff staining showed no significant differences in terms of acute rejection among the 3 surgical methods (all P >0.05)., Conclusions: All 3 surgical methods are able to successfully establish mouse kidney transplantation models, with no significant differences observed in the short-term graft survival and acute rejection. The modified abdominal suture technique and abdominal cuff technique have their respective advantages in research applications. The novel cervical cuff technique for ectopic kidney transplantation model is relatively simple to be prepared and causes less trauma to the mice, providing more options for studies involving xenotransplantation, secondary transplantation, and local lymphatic drainage. However, the difficulty in harvesting the donor kidney and the high incidence of ureteral infections need further validation in long-term survival. This study holds important reference value for choosing the type of mouse kidney transplantation model for different research needs.

Infectious diseases are the leading cause of death in children. Sepsis is a critical infectious disease that causes death in children globally, with a high morbidity and mortality rate. It poses a serious threat to children's health. Early diagnosis has become the key to treating severe sepsis. The establishment of animal models of sepsis can help people better diagnose sepsis and take interventions to improve the prognosis of sepsis patients. This study reviews the types, advantages and disadvantages of existing animal models of sepsis and proposes the optimization of these models to provide a reference basis for the selection and optimization of experimental models and the promotion of the "reverse transformation" of sepsis into clinical practice.

Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder, always deemed to be an insurmountable peak in the field of pain research and treatment. The pain is recurrent, abrupt in onset and termination similar to an electric shock or described as shooting. A poor quality of life has been attributed to trigeminal neuralgia, as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity, such as talking, washing face, chewing and brushing teeth in daily life. The pathogenesis of trigeminal neuralgia has not been fully elucidated, although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder. In addition, orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury. Based on current hypotheses regarding the potential causes, a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia, including models of compression applied to the trigeminal nerve root or trigeminal ganglion, chronic peripheral nerve injury, peripheral inflammatory pain and center-induced pain. However, it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms. The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia. Therefore, it is necessary to discuss the characteristics of the animal models in terms of animal strains, materials, operation methods and behavior observation, in order to gain insight into the research progress in animal models of trigeminal neuralgia. In the future, animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed, with the aim of making valuable contributions to the relevant basic and translational medical research.

Objective To study the correlation between the movement distance of small intestinal contents and survival time in female SD rat models after one-time satiation, and to evaluate its application value for postmortem interval estimation. Methods Adult female SD rats were randomly divided into postprandial groups （1, 2, 3, 4 and 5 h after feeding） and control group. The postprandial groups were fed for 1 h, meanwhile control group was kept fasting. All rats were sacrificed at the given time. The contents in stomach and small intestine were observed, described, compared and photographed, and the movement distance of small intestinal contents was measured. The data of postprandial groups were analysed by one-way analysis of variance. Results The stomach and duodenum of control group were empty with a little thin and yellow small intestinal liquid. The gastral cavities of 1 h postprandial group were full of undigested food. The evolutionary changes of character, colour and content were observed in the gastric and small intestinal contents of other postprandial groups. The movement distance of intestinal contents increased while the empty part decreased gradually. The differences among the postprandial groups were statistically significant （P

BACKGROUND: Osteoporosis, known as “a quiet epidemic disease”, is an “invisible killer” that impairs the health of the elderly. Fracture as the most dangerous complication of osteoporosis is not only a medical problem, but also a serious social problem. OBJECTIVE: To summarize the selection, establishment methods, characters and evaluation of the animal model of osteoporosis. METHODS: A computed-based search of CBM, WanFang, VIP, CNKI and PubMed databases was conducted for the relevant articles published from January 1986 to December 2016 using the keywords of “osteoporosis, animal models” in English and Chinese, respectively. Finally 39 articles were included for result analysis after reading the title and abstract. RESULTS AND CONCLUSION: Animal experiments play an important role in the studies of osteoporosis, so a desirable animal model should hold similarity, reliability, repeatability, applicability, controllability, efficacy and economy. Osteoporosis is a progressive and long-lasting disease that has different characteristics at different stages. But an animal model only simulates one etiology, one stage, major symptoms and pathophysiological changes, and cannot exhibit the whole pathological changes. The current study suggests that animal species and modeling methods can affect the characters of models, and there is a lack of standards for animal age, feeding methods, modeling time and assessment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Interleukin-17A has been shown to play an important role in nerve regeneration following corneal injury. OBJECTIVE: To investigate the effect of interleukin-17A on mouse nerve regeneration after optic nerve injury. METHODS: The interleukin-17A-overexpressed adenovirus vector (AV-IL-17A-GFP) was constructed and purified. Adenoviruses with green fluorescent protein (AV-GFP) served as control group. PC12 cell lines were transfected with adenoviruses and the expression efficiency of IL-17A were detected by ELISA. The adenovirus was intravitreally injected into the mouse vitreous body, and the expression level of IL-17A in the optic nerve was determined by immunofluorescence. Afterwards, a mouse model of optic nerve injury was established to observe the nerve regeneration. RESULTS AND CONCLUSION: ELISA results showed that IL-17A was highly expressed in the PC12 cell lines transfected with AV-IL-17A-GFP compared with the control group. Immunofluorescence results revealed that IL-17A was expressed in vivo successfully. There was a significant increase in the number of regenerated axons in the AV-IL-17A-GFP group compared with the control group (P < 0.05). To conclude, AV-IL-17A-GFP can be expressed in the mature neurons in vivo and promote the axon regeneration after optic nerve crush injury in mice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Repair of tendon interface is a difficulty in orthopedics and sports medicine, and the formation of new bone is conducive to its healing. Calcitonin gene-related peptide (CGRP) plays a critical role in tissue homeostasis and repair, but its effect on the bone-tendon interface repair is unknown. OBJECTIVE: To investigate the effect of CGRP on the expression of osteocalcin and to evaluate the effect of CGRP on the early healing of rotator cuff injury in a mouse model. METHODS: A mouse model of supraspinatus insertion-humerus injury was created. All model mice were then randomized into two groups, and given the injection of 5 nmol/kg CGRP (experimental group) or same volume of normal saline (control group) through the glenohumeral joint immediately after operation, thrice weekly, for 2 weeks. The mice were sacrificed at postoperative 4 and 6 weeks to remove the rotator cuff samples for hematoxylin-eosin staining and biomechanical test. The mRNA and protein expression levels of osteocalcin were surveyed by qRT-PCR, immunohistochemistry, and western blot assay. RESULTS AND CONCLUSION: At postoperative 4 and 6 weeks, the mRNA and protein expression of osteocalcin in the experimental group were significantly higher than those in the control group (P < 0.05). Compared with the control group, there were more fibrocartilages in the experimental group at 4 weeks postoperatively, and more new bone formation in the experimental group at 6 weeks postoperatively. At 4 weeks postoperatively, failure load in the experimental group increased slightly, but it was not significantly different from that in the control group (P > 0.05); at 6 weeks postoperatively, failure load in the experimental group was significantly higher than that in the control group (P <0.05). To conclude, local injection of CGRP can up-regulate the expression of osteocalcin and the formation of new bone at the injury site, which can enhance early healing the injured rotator cuff. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preliminary studies have found that ligustrazine can effectively improve the levels of nitric oxide and prostaglandin E2, and alleviate the inflammatory response of osteoarthritis, but the related mechanism remains unclear. OBJECTIVE: To observe the effect of ligustrazine on the expression levels of type II collagen fiber α 1, vascular endothelial growth factor (VEGF) mRNA and miR20b in the articular cartilage of knee osteoarthritis model, and to explore the mechanism of ligustrazine for early-stage knee osteoarthritis in rats. METHODS: Healthy male Sprague-Dawley rats were randomized into normal, model, high- and low-dose ligustrazine, and positive control groups. Rats in the latter four groups were used to establish the model of early-stage knee osteoarthritis by intra-articular injection of papain, and were then intragastrically given the administration of normal saline, 100 and 50 mg/kg ligustrazine, and 24 mg/kg celecoxib, respectively. The normal group was given the same volume of normal saline. The treatment in each group lasted for 6 weeks. Then, the rat cartilage was taken, and changes of cartilage tissues were assessed by Mankin scores. Expression levels of type II collagen fiber α 1, VEGF mRNA and miR20b in the cartilage were detected by qRT-PCR. RESULTS AND CONCLUSION: The order of Mankin scores was as follows: normal group < high-dose ligustrazine group < positive control group < low-dose ligustrazine group < model group (P < 0.05). The mRNA expression levels of type II collagen fiber α 1 and VEGF were the highest in the normal group, followed by the high-dose ligustrazine group, positive control group, low-dose ligustrazine group, and model group (P < 0.05). The expression level of miR20b was significantly up-regulated except the model group, and its order was follows: high-dose ligustrazine group < positive control group < low-dose ligustrazine group. Our results indicate that ligustrazine has a positive effect on early- stage knee osteoarthritis in rats, and the possible mechanisms by which ligustrazine promotes cartilage repair are to up-regulate miR20b expression and to inhibit VEGF mRNA expression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Edaravone, an effective free radical scavenger, has been reported to significantly improve the rehabilitation of limb locomotion after spinal cord injury (SCI), but the underlying mechanism remains unclear. OBJECTIVE: To explore the mechanism underlying edaravone promoting the recovery of limb locomotion in rats with SCI by observing the Basso, Beattie, Bresnahan scores and expression levels of collagen type I and IV. METHODS: Thirty-six rats were randomly allocated into three groups (n=12 per group): sham group (laminectomy plus intraperitoneal injection of normal saline), model group (SCI model by NYU impactor plus intraperitoneal injection of normal saline), and edaravone group (SCI model by NYU impactor plus intraperitoneal injection of edaravone). All rats were given the administration at the 1st day post-SCI for consecutive 7 days. The Basso, Beattie, Bresnahan scores were tested at 1, 3, 5 and 7 days post treatment. On day 7, all rats were sacrificed to remove the spinal cord, and the morphology of neurons in the spinal cord were observed by Nissl staining; the expression levels of collagen type I and IV were detected by immunohistochemistry and western blot assays. RESULTS AND CONCLUSION: Compared with the model group, the Basso, Beattie, Bresnahan scores in the edaravone group were significantly increased at day 5 post treatment (P < 0.05). Nissl staining showed a clear boundary between grey matter and white matter, and a large nucleolus in the neurocytoplasm in the sham group; there was a complete structure of neurons, slight cellular swelling and small hematoma area in the edaravone group; many and large cavitations and swollen nucleus were found in the neurons, even without nucleolus. Immunohistochemistry and western blot assay results showed that the expression levels of collagen type I and IV in the edaravone group were significantly higher than those in the model group (P < 0.05). These results indicate that edaravone can promote the recovery of limb locomotion of rats with SCI, probably via up-regulating the expression levels of collagen type I and IV. [ABSTRACT FROM AUTHOR]

BACKGROUND: Open facture is easy to induce infection, which is an urgent problem in clinic. Establishing a reliable animal model of open fracture with infection is of great significance for drug and instrument development and application. OBEJCTIVE: To develop an open fracture with infection model in New Zealand white rabbits, and to identify the available number of bacteria that can cause infection. METHODS: The amount of bacteria was determined by establishing open fracture structure and verifying the concentration of bacterial colonies. Thirty New Zealand white rabbits were randomly divided into control group and four experimental groups, and a transverse fracture at the middle part of tibia was established in all rabbits, followed by the injection of 1 mL of normal saline or 1mL of Staphylococcus aureus suspension at the concentrations of 1×105, 1×106, 5×106, and 1×107 CFU/mL. Afterwards, the optimal concentration of 1 mL of bacteria liquid causing infection was determined by gross observation, body temperature analysis and body mass measurement, white blood cell and C-reactive protein detection, bacterial culture and pathological observation. RESULTS AND CONCLUSION: Rabbits in the 5×106 CFU/mL group were all infected and had higher survival rate. In the 1×105 and 1×106 CFU/mL groups, some rabbits showed no infection. One rabbit died due to infection in the 1×107 CFU/mL group. In summary, the reliable infection model of open fracture can be induced by injected with 1 mL of Staphylococcus aureus at the concentration of 5×106 CFU/mL in New Zealand white rabbits, which can be used as an effective model to guide drugs and instruments related anti-infective research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is thought to be caused by trauma to dentoalveolar structures after dental extraction and implantation that have a limited capacity for bone healing followed by infection, suppuration and pain, further inducing equestration, but the pathogenesis is poorly understood. OBJECTIVE: To establish a stable animal model of BRONJ, and to observe its clinical manifestations, radiological changes and pathological characters, thereby paving ways for further understanding the pathogenesis of BRONJ. METHODS: Twenty-four female Sprague-Dawely rats were randomly allocated into experimental and control groups (n=12 per group). The rats in the experimental group were given the intraperitoneal injection of 0.2 mg/kg zoledronic acid, and the controls received the intraperitoneal injection of same volume of normal saline, three times weekly for consecutive 12 weeks. Subsequently, left first mandibular molars were extracted under general anesthesia, and the bone healing was observed. At 8 weeks after tooth extraction, all the rats were euthanized. The rat left jaws were examined by X-ray and micro-CT to explore the imaging changes. The histopathological characteristics of the mandibular soft and hard tissues were investigated by hematoxylin-eosin staining and Masson staining, to further testify the BRONJ model. RESULTS AND CONCLUSION: At 8 weeks after tooth extraction, the wound was unable to heal, and nonvital bone tissues were visible in the experimental group. The findings revealed on radiographies and pathological sections were in accordance with the characteristics of BRONJ. Masson staining results showed slender collagen fibrils around the dental extraction wound were slender in the experimental group. These results indicate that the intraperitoneal injection of zoledronate combined with tooth extraction can induce BRONJ in rats. The soft tissue toxicity and anti-angiogenesis of zoledronic acid can promote the occurrence of BRONJ, and the local acidic microenvironment caused by trauma probably is involved in the occurrence of BRONJ. [ABSTRACT FROM AUTHOR]

BACKGROUND: Synovitis plays an important role in the occurrence and development of early knee osteoarthritis. OBJECTIVE: To compare synovial inflammation in a rabbit mode of knee osteoarthritis induced by injecting low concentration of papain at different time points, thus providing reference for the study on synovitis in knee osteoarthritis. METHODS: Twenty-four New Zealand white rabbits were divided randomly into four groups, and received the injection of 0.5 mL mixture of 2% papain with 0.03 mol/L L-cysteine into the right knee at 1, 4 and 7 days, respectively. The model rabbits were respectively sacrificed at 1, 2 and 3 weeks after the last injection, and the rabbits in the blank control group were killed at 3 weeks. The local skin temperature and circumference of the knee were recorded, and the synovium and infrapatellar fat pad were separated from the right knees for histopathological observation and ELSA. RESULTS AND CONCLUSION: At the 1st week after modeling, joint effusion was significantly increased, local skin temperature and circumference of knee joint were higher than those at the 2nd, and 3rd weeks. The levels of interleukin-1, tumor necrosis factor-α and matrix metalloproteinase-13 in the synovium in the three experimental groups were higher than those in the blank control group at 1, 2 and 3 weeks after modeling; the levels peaked in the 1st week, but no significant fluctuation appeared in the 2nd and 3rd weeks. There were synovial tissue hyperplasia, thickening, and inflammatory cell infiltration in the 1st, 2nd and 3rd weeks, and the proliferation of synovial tissue increased significantly with time. These findings indicate that the intra-articular injection of low concentration of papain and 0.03 mol/L L-cysteine mixtures contributes to a rabbit model of knee synovial inflammation within 1 week, with significantly joint effusion. However, significant synovial tissue thickening and vascular hyperplasia are observed; meanwhile, the joint effusion is decreased obviously. [ABSTRACT FROM AUTHOR]

BACKGROUND: Corneal repair materials can be used as an alternative of human donor corneas to repair corneal injuries, but their evaluation of effectiveness is necessary before entering clinical trials. Unfortunately, there is no standardized method for effectiveness evaluation until now. OBJECTIVE: To establish and validate a corneal fungal infection model in rabbits and the corneal transplantation method. METHODS: Twelve New Zealand White rabbits were selected to establish a corneal fungal infection model in the left eye (experimental) and a normal control in the right eye. Two weeks after modeling, acellular porcine corneal stroma was transplanted into the left eye. After transplantation, slit lamp microscope test, corneal thickness detection, intraocular pressure measurement, confocal microscopy test and optical coherence tomography were performed. Then the degree of transparency, degree of epithelium healing, degree of edema, degree of corneal neovascularization and degree of material thawing were evaluated. The corneal pathological sections with hematoxylin-eosin staining were observed at 3, 6 and 12 months after surgery. RESULTS AND CONCLUSION: (1) The corneal thickness increased significantly at 1 month after transplantation, varied slightly within 3-6 months, and became close to the normal value at 1 year. (2) The intraocular pressure of the left eye was close to normal eyes. (3) Findings from the optical coherence tomography showed that the repair materials fit well with the implantation bed at 7 days after transplantation; the transplanted area was fully covered with epithelial cells at 6 months after transplantation, and the uniform thickness of the repair material in the transplanted area was detected; the grafted cornea was restored to normal cornea at 1 year after transplantation. (4) Under the confocal microscope, the repair materials in the transplanted area were evenly spread at 1 month after transplantation; few cells migrated into the transplanted area at 6 months after transplantation; the density of epithelial cells was increased, and there were migrated cells in the transplanted cells, but the cell number was less than that of normal eyes at 1 year after transplantation. (5) The corneal repair material was almost completely transparent at 1 year after transplantation, indicating its effectiveness in the treatment of infectious corneal ulcers. No rejection occurred, indicating that the corneal healing material is well-curative. (6) At 3 months after transplantation, a large number of stromal cells migrated to the corneal substitute, and the collagen fibers in the transplanted area were arranged neatly and densely without obvious scarring and degradation. At 6 months after transplantation, the transplanted area basically recovered. At 1 year after transplantation, the transplanted area was fully restored to the normal cornea state with good biocompatibility. Our experimental findings indicate that the rabbit model of corneal fungal infection and the corneal transplantation method can be used to evaluate the effectiveness of such corneal materials. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that dental pulp stem cells have high proliferation and multi-directional differentiation abilities and can differentiate into a variety of cells under certain conditions. At present, the use of dental pulp stem cells to construct tissue-engineered dentin-pulp complex is expected to become a new strategy for human dental defect repair . OBJECTIVE: To observe the effect of dental pulp stem cells on the repair of rat tooth defects by construction of tissue-engineered dentin-pulp complex. METHODS: Twenty-four Sprague-Dawley rats were used to make animal models with dental pulp removal, and then model rats were randomly divided into model group and transplantation group. Rats in the transplantation group were subjected to tissue-engineered dentin-pulp complex transplantation, and those in the model group given no treatment. Tooth samples were collected at 3, 5, 7 weeks post transplantation and observed using hematoxylin-eosin staining and immunofluorescence staining. The dentin thickness of rats was measured by Image Pro Plus 6.0 image software system. RESULTS AND CONCLUSION: (1) Dental pulp cells was mostly spindle/oval-shaped and partially polygonal. The third generation of cells with long spindle shape showed fibrous growth and uniform morphology. Findings from immunohistochemical staining showed spindle-shaped deep-colored cells with oval nuclei stained as dark blue were identified as fibroblast-like cells, and were positire for vimtin. (2) Findings from hematoxylin-eosin staining showed vacuolar degeneration of the cells, and hbdestroyed pulp tissue and debris, irregular cord-like tissue, and a large amount of red blood cells and inflammatory cells in the pulp cavity, accompanied by clearly visible vascular dilation. Seven weeks after transplantation, a bundle of odontoblasts were visible in the matrix-like tissues of the dentin, and there was a distinct boundary between the original dentin and regenerated dentin. (3) Findings from immunofluorescent staining showed that after dentin-pulp complex transplantation, the number of cells in the pulp cavity increased significantly at 3 weeks, and there was also a substantial increase in dental pulp cells at 5 weeks that were distributed on the wall of the pulp cavity. Compared with the model group, the dentin thickness in the transplantation group was significantly higher at each time after transplantation (P < 0.05), and in the transplantation group, there was also a significant difference in the dentin thickness at different time points (P < 0.05). To conclude, the tissue-engineered dentin-pulp complex can promote dentin regeneration and repair. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is little information available in the mechanism of radiation-induced salivary gland injury, and its treatment and prevention are still at the exploratory stage. OBJECTIVE: To establish a rat model of radiation-induced xerostomia with 18 Gy electron beam and to observe the pathological changes of the submandibular gland and changes in saliva ingredients. METHODS: Totally 115 Wistar rats were randomly divided into exposure and control groups: the rats in the exposure group were subjected to anesthesia, and the submandibular gland received 18 Gy electron beam radiation to establish the model of radiation-induced xerostomia. The rats in the control group were only anesthetized but not exposed to radiation. The water intake was recorded at 21 dys after modeling. The saliva was collected and the submandibular gland was removed at 1，3, 7, 14, 21，28, 35 and 42 days to detect the saliva volume and submandibular gland index, and the morphological changes of the submandibular gland were observed by hematoxylin-eosin staining. RESULTS AND CONCLUSION: At 1-21 days after modeling, the average daily water intake was (6.42±1.91) mL in the exposure group and (4.82±1.20) mL in the control group, respectively (P < 0.05). During 42 days after modeling, the saliva secretion volume in the exposure group was lower than that in the control group, which was the lowest on day 7, and the difference was significant at 7, 21，28 and 42 days after modeling between two groups (P < 0.05). The submandibular gland index in the exposure group was significantly lower than that in the control group at 1 and 21-42 days after modeling (P < 0.05). Hematoxylin-eosin staining results showed that in the exposure group, the rat submandibular gland appeared with inflammatory infiltration, glandular atrophy and karyopyknosis that were aggravated with time until day 42. To conclude, the rat model of radiation-induced xerostomia is established successfully with 18 Gy beam, characterized as increased water intake, decreased saliva volume and progressive aggravation of pathological injury of the submandibular gland. [ABSTRACT FROM AUTHOR]

BACKGROUND: Unclear pathogenesis of osteoarthritis results in a lack of radical therapy. The current studies mainly focus on pain relief and joint function improvement. Establishing an animal model is helpful to explore the pathogenesis, prevention and treatment of osteoarthritis, and also contributes to develop health food with new functions used for preventing and improving osteoarthritis. OBJECTIVE: To overview the establishment of the osteoarthritic animal model and its application in functional food research, thereby providing scientific basis for reasonable selection of osteoarthritic animal models and screening tests of bioactive substances. METHODS: CNKI and PubMed databases were retrieved for the articles related to animal model establishment published before May, 2016, using the keywords of “osteoarthritis, animal model” in Chinese and English, respectively. Totally 157 articles were searched initially after repetitive ones excluded, and then 59 eligible articles were included. RESULTS AND CONCLUSION: Animal models of osteoarthritis are established in a variety of ways, and have their own advantages and disadvantages, with different application scopes. Therefore, we need select and establish appropriate animal models used for studying the pathogenesis of osteoarthritis and screening more specific and effective substances that can prevent and improve osteoarthritis. Additionally, it is of great significance for further developing the corresponding functional health food to alleviate the patients' pain and improve their quality of life. [ABSTRACT FROM AUTHOR]

BACKGROUND: Animal models of osteoarthritis are of great significance for the studies on its pathogenesis, prevention and treatment. There are various osteoarthritis models that certainly simulate the development of human osteoarthritis. Some stimulating factors have been found to participate in the occurrence and development of osteoarthritis. OBJECTIVE: To review the recent researches about animal models of osteoarthritis at home and abroad, and to assess different modeling methods and some stimulating factors related to the occurrence and development of osteoarthritis. METHODS: A computer-based retrieval of CNKI and PubMed databases before December 2016 was performed with the keywords of “osteoarthritis, animal models, stimulating factors, assessment grading system, outcome measurement” in Chinese and English, respectively. Finally 57 eligible papers were included for analysis. RESULTS AND CONCLUSION: (1) In recent years, the osteoarthritis models are mainly established by doing damage to the cruciate ligaments and meniscus, and evaluated by Mankin score; the age of experimental animals tend to be younger. (2) Animals developed maturely are rational, so as to avoid the effect of self-healing caused by growth factors on osteoarthritis occurrence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whether one-stage bone healing with red bone marrow or mesenchymal stem cell transplantation is needed? Whether closed reduction with intramedullary interlocking nailing combined with autologous red bone marrow transplantation can promote osteogenesis in the one-stage treatment of femoral comminuted fracture still remains unclear. OBJECTIVE: To explore the effects of closed reduction with intramedullary interlocking nailing and one-stage treatment with autologous red bone marrow transplantation on fracture healing. METHODS: Twenty healthy New Zealand rabbits were selected and anesthetized, and then the models of femoral comminuted fracture were established at the hinder limbs after throwing a 5 kg of hammer from 30 cm height. All rabbits underwent intramedullary fixation using Kirschner wire (diameter: 2 mm); the right limbs served as control groups, and the left limbs as transplantation group, subjected to the injection of autologous red bone marrow (1 mL) into the fracture region. Then the rabbits were respectively killed at 14, and 28 days after modeling, the thickness of thickest callus was measured on X-ray films, and the number of chondrocytes and relative area of bone trabecula in the fracture region were observed through hematoxylin-eosin staining under light microscope. RESULTS AND CONCLUSION: (1) The thickness of callus formation in the control group was significantly less than that in the transplantation group at 14 days after modeling (P < 0.01). (2) The number of chondrocytes in the transplantation group was significantly more than that in the control group at 14 days after modeling (P < 0.01), and the fracture healing in the transplantation group was faster that in the control group. (3) Compared with the transplantation group, the relative area bone trabecula in the fracture region in the control group was significantly reduced at 28 days after modeling (P < 0.01). (4) These finding indicate that red bone marrow transplantation promotes fracture healing in the intramedullary fixation for femoral comminuted fracture in rabbits. [ABSTRACT FROM AUTHOR]

BACKGROUND: An ideal animal model is important for studying gouty arthritis. However, a lack of perfect animal model of gouty arthritis delays the progress in searching for a novel drug and treatment method. OBJECTIVE: To evaluate the effectiveness of the modified rabbit model of gouty knee arthritis. METHODS: New Zealand white rabbits were selected and randomly divided into four groups. Except blank control group received no intervention; the rabbit greater omentum was removed, which was wrapped with nothing (sham operation group), implanted with 0.1 g/L monosodium urate crystal suspension (conventional group), or 100 mg/kg monosodium urate crystal (modified group) into the suprapatellar cyst of the rabbit right knee. The swelling degree, motor function, and inflammatory response of the knee joint were observed at 1, 2 and 3 days, 1, 2, 3, and 4 weeks after modeling to evaluate the advantages and disadvantages of the modified model. RESULTS AND CONCLUSION: The movement function in the modified group was significantly decreased within < weeks after modeling (P < 0.05). The joint swelling index in the conventional and modified groups peaked on day 1 or 2, and then began to decrease. The descent velocity in the modified group was slower than that in the conventional group, and the swelling index showed significant difference between modified and blank control groups at 4 weeks after modeling (P < 0.05). The conventional and modified groups presented with overt inflammatory response, synovial hyperplasia, congestion and edema; abundant synovial fluid appeared in the articular cavity; periphery tissue became congestion and edema; the cartilage revealed no obvious damage. The levels of interleukin-6 and -1β in serum and synovial fluid in the conventional and modified groups peaked on days 1 and 2, followed by a decrease, but the modified group exhibited a slower descent velocity compared with the modified group. All above levels in the modified group were significantly higher than those in the other three groups (P < 0.05). These results suggest that the rabbit model of gouty knee arthritis is successful established by the intra-articular implantation with the autogenous greater omentum-wrapped monosodium urate crystal, which can last more than 4 weeks, longer than the conventional model. [ABSTRACT FROM AUTHOR]

BACKGROUND: Different anesthesia methods significantly impact mean arterial pressure, systolic and diastolic blood pressure, arterial blood pH and blood viscosity, but what kind of anesthesia method is more suitable for preparation of animal model does not reach an agreement. OBJECTIVE: To compare the effectiveness of local anesthesia and general anesthesia for preparation of rabbit intervertebral disc degeneration model in procession of percutaneous acupuncture rotary cut. METHODS: A total of 48 New Zealand white rabbits were randomly divided into the local anesthesia group and the general anesthesia group. The local anesthesia group was anesthetized with 0.5% lidocaine. The general anesthesia group was intraperitoneally injected with 3% sodium pentobarbital (30 mg/kg). In the two groups, models of intervertebral disc degeneration were established by minimally invasive percutaneous acupuncture rotary cut at L4/5, L5/6 levels. Modeling time was observed in both groups. Disc degeneration was evaluated by the gross observation, MRI detection, and histopathological examination at 4, 8, 12, and 16 weeks after modeling. RESULTS AND CONCLUSION: (1) General observation: the nucleus pulposus gradually with darker color and elasticity reduced in two groups after modeling. (2) MRI T2-weighted image results showed no significant changes in disc signal intensity at early stage, but the signal strength showed a decreasing trend with time. (3) Disc degeneration was evaluated according to Pfirrmann grading. Disc degeneration was gradually increased with time in two groups (P < 0.05), but there was no significant difference at postoperative time points in both groups (P > 0.05). (4) Masson staining showed that different degrees of annulus irregular arrangement appear in the two groups 8 and 12 weeks after modeling, but the structure was still intact. 16 weeks later, annulus disorganized, or even breakage in the two groups; no significant difference was detected between the two groups. (5) Safranin O staining showed that nucleus pulposus cells were not significantly reduced in the two groups at 4 weeks, but were significantly reduced at 16 weeks. (6) The average modeling time of local anesthesia group [(15.24±2.67) minutes] was significantly shorter than that in the general anesthesia group [(25.64±6.85) minutes] (P < 0.05). These results indicate that intervertebral disc degeneration model can be successfully established by minimally invasive percutaneous acupuncture rotary cut by using local anesthesia and general anesthesia; however, local anesthesia has a shorter operating time and simple anesthetic procedure. The efficacy was identical between the two methods. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mechanisms related to bone fracture and nonunion have been clarified, but the healing time and treatment strategy of delayed union remain controversial. OBJECTIVE: To establish a reliable model of femoral delayed union using external fixation in the New Zealand white rabbit. METHODS: Seventy-two New Zealand white rabbits were randomized to three groups. After removal of 10-mm femoral middle bone cortex with internal and external periosteum and bone marrow, a uniplanar external fixator was used. There was a 1 mm gap between broken ends (group A), and the broken ends were sealed by bone wax (group B). For controls, only bone cortex was cut and then fixed to contact the broken ends. The gross, radiological and histological observations were performed to observe the bone healing at 4, 8 and 12 weeks after modeling. RESULTS AND CONCLUSION: The control group achieved bone healing at the 4th week, which was considered as the normal time of bone healing. The groups A and B achieved healing at the 12th week, which was remarkably longer than that in the control group. The rabbit femoral delayed union model showed the typical X-ray imaging and pathological features of delayed union. Our results suggest that the model is reasonable and reliable, which can provide reference for clinical research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Distraction osteogenesis is an effective method for large bone defects, bone tumors and osteomyelitis. However, there is a lack of a standard model in the basic research concerning distraction osteogenesis. OBJECTIVE: To establish a rabbit femoral model of distraction osteogenesis and to assess its osteogenic effect. METHODS: Twenty male New Zealand rabbits were enrolled to establish the rabbit femoral model of distraction osteogenesis using a novel distractor. Subsequently, the gross observation and X-ray examination of the specimens were performed to assess the osteogenic effect. RESULTS AND CONCLUSION: Gross observation: on day 14 after fixation, there were light-colored and dense newborn bones distributing evenly in the distraction gap, and appeared with a columnar connection with the broken ends; the boundary with normal bones became vague. On day 35, the surface of newborn bones in the distraction gap showed the same color and texture with the normal ones, the boundary between the newborn and normal bones was difficult to distinguish, and the bone mineral density was increased notably. Radiology results: on day 14 after fixation, the stent was fixed stably, the broken ends got good reduction, and cloudy shallows connecting the two ends of the normal bones in the distraction gap and increased bone mineral density were detectable. Completely calcified new-born bones, intact bone cortex and open medullary canal were further visible on day 35. These results suggest that the rabbit femoral model of distraction osteogenesis is established successfully using the self-designed single-arm distractor based on rational surgical procedures and standard operations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Some studies have focused on bone marrow mesenchymal stem cells (BMSCs) combined with allograft bone or artificial bone substitute materials for bone defect repair. But there is no report on BMSCs combined with Bio-oss for repair of rabbit skull defects as yet. OBJECTIVE: To observe the effect of BMSCs combined with Bio-oss in repairing skull defects in rabbits. METHODS: BMSCs from male rabbits were isolated, cultured, and used as seed cells. In the skull of the female rabbits, three full-thickness bone defects with the same external diameter of 6 mm were made by a ring bone drill. Ninety-six female rabbits were randomly divided into four groups, and given Bio-oss/BMSCs in combination group, Bio-oss alone in Bio-oss group, BMSCs implantation in BMSCs group, and no intervention in blank group. All the implant surfaces were covered with guided tissue regeneration membrane. RESULTS AND CONCLUSION: The osteogenic effect in the combination group was better than that in the other three groups, and the Bio-oss group showed better osteogenesis in comparison with BMSCs and blank groups. But there was no significant difference between the BMSCs and blank groups. These findings indicate that the combined use of BMSCs as seed cells and Bio-oss as a scaffold material exerts overt osteogenic effects in rabbit skull defect area, which provides a new idea for the clinical treatment of bone defects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Morphological characteristics of the rabbit lumbar vertebrae are of great significance for animal experiments about lumbar spine, but there is a lack of study on the lumbar morphology in rabbits. OBJECTIVE: To establish a three-dimensional model of rabbit lumbar vertebrae, and to observe its morphological characteristics, thereby providing anatomical basis for the animal experiments about lumbar spine. METHODS: Twenty New Zealand rabbits were subjected to 64-row multi-detector CT (Siemens) scan, and the three-dimensional models were constructed based on the CT data from 140 lumbar vertebrae. The morphological parameters of L1-7 were measured, and the internal and external structures of lumbar vertebrae and changes of different segments were observed. RESULTS AND CONCLUSION: (1) Changes of the morphological parameters of each lumbar vertebra: the L1-7 height first increased and then decreased, and the shortest height was in the L7, which was (1.12±0.18) cm. L1 vertebral body exhibited the shortest transverse diameter, (1.03±0.15) cm, and the longitudinal diameter did not differ significantly among vertebrae. The transverse and longitudinal diameters of L1-6 spinal canals were on a rise, but decreased abruptly at L7. The pedicle width of L1-7 increased gradually; the pedicle height of L1-5 increased gradually, and then began to decrease markedly, and the shortest at L7, (0.58±0.11) cm. The width and length of L1-6 spinous process increased steadily, but decreased at L7. The length of L1-3 transverse process increased gradually, tended to be steady at L3-6, and increased notably at L6-7; there were significant differences in the transverse process angle at L1-6, but the angle increased markedly to (58±2)° at L7, (2) These results indicate that the internal and external structures of lumbar vertebrae and changes of different segments are obtained through morphological measurement of lumbar vertebrae in New Zealand white rabbit, which provides a detailed anatomical data for relative animal experiments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Annulus puncture method is commonly reported in the establishment of intervertebral disc degeneration (IDD) models, but there is a lack of comparative studies concerning complete MRI, pathologyical and extracellular matrix changes. Thereafter, a further exploration is imperative. OBJECTIVE: To investigate the feasibility of establishing IDD models using annulus puncture. METHODS: Thirty New Zealand white rabbits were randomly divided into two groups (n=15 per group). In experimental group, through extraperitoneal approach, the L1-2, L2-3, and L3-4 intervertebral space were exposed, and then stabbed by 16-gauge hypodermic needles; while rabbits in sham operated group were only subjected to making and incision but not to puncture. Five rabbits in each group were randomly selected for MRI examination at 4, 8 and 16 weeks after modeling, and were sacrificed through air embolism to obtain the nucleus pulposus. Histological changes were observed by hematoxylin-eosin staining, and the level of proteoglycan was detected by Safranin O staining. RESULTS AND CONCLUSION: In the experimental group, T2-weighted signal in the disc was decreased in a time-dependent manner; an obvious reduction was found at 4 weeks after modeling, and reached the peak at 16 weeks. In contrast, the sham operated group showed no significant changes at each time point. Hematoxylin-eosin staining showed that in the experimental group, cartilage-like cells decreased, while fibroblast-like cells in the disc increased in number and proportion, and extracellular fibers were in disorder; all above changes became obvious at 4 weeks after surgery and the most obvious at 16 weeks, but there were no significant changes in the sham operated group. Safranin O staining revealed that the color of the tissues under puncture became lighter, and this variation became overt at 4 weeks after surgery and the most obvious at 16 weeks. In conclusion, annulus puncture is a reliable method to make IDD models. [ABSTRACT FROM AUTHOR]

BACKGROUND: Abnormal stress is an important factor causing intervertebral disc degeneration. To establish an ideal in vivo animal model of intervertebral disc degeneration is of great significance for in-depth study on the related pathogenesis. OBJECTIVE: To develop an in vivo rabbit intervertebral disc model and to investigate the relationship between continuous tensile load and intervertebral disc degeneration. METHODS: Twenty-five New Zealand white rabbits aged 6 months old were randomly divided into three groups: blank control (n=5), sham (n=10) and experimental (n=10) groups. The blank control group received no intervention, and the L4/5 segments were removed at the 1st day. The intervertebral disc assistor was used to fix the L4 and L5 vertebral bodies in the experimental and sham groups, the L4/5 segments in the experimental group were loaded 1 MPa axial tensile force, and the L4/5 segments in both two groups were then removed at 14 and 28 days. The changes of L4/5 intervetebral space height and surrounding bone substance were observed by X-ray examination, the morphological changes of the intervertebral disc were observed by hematoxylin-eosin staining, the cell survival was detected by nitro blue tetrazolium staining and mRNA expression levels of aggrecan, collagen type II and SOX9 in the intervertebral disc tissues were assessed by RT-PCR at each time point. RESULTS AND CONCLUSION: The radiological manifestations, histological changes, cell survival and mRNA expression levels of aggrecan, collagen type II and Sox9 showed no significant difference between the blank control and sham groups. Comparied with the blank control group, in the experimental group, the L4/5 intervertebral space was narrowed with time, the articular surface was coarse, and the upper and lower corpus vertebrae edge appeared to have lip-shaped hyperplasia; the intervertebral disc cells distributed irregularly; the nucleus pulposus was in dehydration and deflation, annulus fibrosus arranged irregularly, and the vacuoles in notochord cells tended to disappear; the expression levels of aggrecan, collagen type II and SOX9 were markedly downregulated. These findings suggest that the in vivo rabbit model of intervertebral disc is successfully established, in which continuous mechanical tensile load is further proved to directly cause intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Establishment of lumbar disc degeneration in animal models can help doctors understand the development rules and pathophysiological changes of this disease, and can explore and research more rational treatment by creating animal models. OBJECTIVE: To review recent advances in vivo model of lumbar disc degeneration. METHODS: The first author used the computer to search related articles on PubMed database and Chinese Journal Full-text Database from inception to May 2016. The search key words were “lumbar disc, degeneration, animal model, vivo model”. A total of 161 related articles were retrieved and 49 of them met the inclusion criteria. RESULTS AND CONCLUSION: (1) Building an intuitive and reliable animal model of lumbar disc degeneration will not only help the basic research of degenerative disc disease, but also provide a good experimental carrier for the repair treatment of degenerative lumbar disc. (2) After more than 80 years of development, the animal model of lumbar disc degeneration has formed a production mode of “more species, more methods and newer ideas”. Current models have their own advantages, cannot be replaced. However, problems such as poor controllability, low degree of safety or long observation period are still exiting more or less. All these need further research and exploration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ankylosing spondylitis is a chronic inflammatory antoimmune disease involving the axial skeletion. So far, the pathogenesis of the disease is not clear. It still needs to build a more mature and stable animal model to promote further research. Since human tissue specimens of the spine and sacroiliac joint are very difficult to obtain, research has been hinders by limits availability of tissue samples from patients. The understanding of ankylosing spondylitis pathogenesis greatly depends on ankylosing spondylitis animal models. Howerer, the several animal models we have today cannot very good represent ankylosing spondylitis pathogenesis and disease progress. OBJECTIVE: To summarize clinical and pathological characteristics of animal models of ankylosing spondylitis to further provide the basis for further improvement of this animal model. METHODS: The databases of PubMed/CNKI were retrieved with key words of “Ankylosing Spondylitis, Animal Models, HLA-B27”. We excluded clinical research of new drugs and studies in animal models for the research methods or studies that did not mention the mechanism of animal models. Pathogenesis and pathological characteristics of animal models of ankylosing spondylitis were summarized. RESULTS AND CONCLUSION: This review included 37 studies and summarized three kinds of animal models of ankylosing spondylitis. All kinds of animal models have their own characteristics and disadvantages. They can simulate some features of ankylosing spondylitis. But to some extent, there is still lack of animal models of representing ankylosing spondylitis. The incidence of ankylosing spondylitis is closely related to the intestinal flora. The combination of different types of animal models is possible to reproduce more stable and perfect animal model of ankylosing spondylitis. [ABSTRACT FROM AUTHOR]

Animal study plays a key role to evaluate the safety and effectivity of medical devices. This study aims to share evaluated consideration on the role, general principles, necessity, study design and quality management system of animal study, in order to improve the quality of animal study and reduce unnecessary study.

Primary dysmenorrhea (PDM), cyclic menstrual pain in the absence of pelvic anomalies, is characterized by acute and chronic gynecological pain disorders in childbearing age women. PDM strongly affects the quality of life of patients and leads to economic losses. PDM generally do not receive radical treatment and often develop into other chronic pain disorders later in life. The clinical treatment status of PDM, the epidemiology of PDM and chronic pain comorbidities, and the abnormal physiological and psychological characteristics of patients with PDM suggest that PDM not only is related to the inflammation around the uterus, but also may be related to the abnormal pain processing and regulation function of patients' central system. Therefore, exploring the brain neural mechanism of PDM is indispensable and important to understand the pathological mechanism of PDM, and is also a hotspot of brain science research in recent years, which will bring new inspiration to explore the target of PDM intervention. Based on the progress of the neural mechanism of PDM, this paper systematically summarizes the evidence from neuroimaging and animal model studies.

Pseudomonas aeruginosa ( P. aeruginosa ) is an opportunistic pathogenic bacterium with complex pathogenesis and drug resistance mechanisms. It has high morbidity and mortality and can cause acute and chronic infections in immunocompromised individuals, with lung infections, wound infections, and bloodstream infections being the most common. The animal infection model of P. aeruginosa is of great value for in-depth research on the pathogenicity, drug resistance, and therapeutic measures of P. aeruginosa by simulating the pathways of human bacterial infections. This article firstly summarizes the selection, anesthesia, and disposal of experimental animals in the construction of animal models of P. aeruginosa infection, and then reviews the methods of construction, model evaluation, and applications of animal models of P. aeruginosa pulmonary infection, wound infection, and bloodstream infection, in order to provide a reference for scientific research related to P. aeruginosa infectious diseases.

Contrast-induced acute kidney injury (CI-AKI) refers to acute kidney injury that occurs after intravascular contrast media is applied. It is the third most common cause for acute renal failure in hospitalized patients and can cause severe renal impairment and adverse cardiovascular outcomes. In severe cases, it can even lead to the death of the patient. Due to its complicated pathogenesis, the pathogenesis of CI-AKI has not yet been elucidated. Therefore, it is of great significance to further study the pathogenesis for the prevention of CI-AKI. Moreover, a good animal model of CI-AKI is an important tool for in-depth research on the pathogenesis of acute kidney injury induced by contrast agents.

As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.

Objective To investigate the feasibility and stability of medical gas suction feeding device for copying the model of respiratory failure in dogs. Methods The self-designed medical gas suction feeding device was used to establish the model of respiratory failure in dogs. After regulating the proportion of oxygen (O2), carbon dioxide (CO2) and nitrogen (N2), the fraction of inspiration O2 (FiO2) was decreased, while the forced inspiratory carbon dioxide (FiCO2) was increased. At the same time, the breathing out pathway was open to make the arterial oxygen partial pressure p (O2) and arterial blood carbon dioxide partial pressure p (CO2) reached and stabilized in a stable condition. The arterial blood samples between default state and 1 hour, 2 hour after modeling were collected to detect the blood gas index. Results One hour after the establishment of model, the p (O2)was ≤ 60 mmHg (1 mmHg=0.133 kPa), and p (CO2) was ≥50 mmHg (1 mmHg=0.133 kPa), which suggested that the dog model of respiratory failure was established successfully. Compared with the basic state, data of pH, oxygen content, oxygen saturation (SaO2) and residual alkali (BE) were decreased at 1 hour and 2 hour after modeling (P < 0.05). The p (O2), oxygen content, SaO2 were decreased in 2 hour after modeling compared with those of 1h after modeling (P < 0.05). There were no significant differences in pH, p (CO2), TCO2, HCO3- and BE between 1 hour and 2 hour after modeling (P > 0.05). Conclusion Under the regulation of the medical gas suction feeding device, the respiratory failure state of large experimental animals is successfully established. [ABSTRACT FROM AUTHOR]

Objective To establish an animal model of annulus fibrosus (AF) partial defect for the repairing of interver⁃ tebral disc (IVD) defect. Methods Image J 1.46r software was used to measure the T12/L1-L6/S1 intervertebral height in ovine lumbar spine X-ray films. AF thickness was measured by axial split disc. A 11 blade was used to make a trapezoid de⁃ fect of upper bottom 3 mm, lower bottom 5 mm, height 5 mm and thickness 3 mm, whose lower bottom toward the nucleus pulposus (NP) in the left front of ovine lumbar IVD in vitro. The minimally invasive lateral approach was used to make the same type of trapezoid defect in the left front of the ovine lumbar IVD in vivo. The trapezoidal defect length of the axial divid⁃ ing disc was measured, AF and a small amount of NP from trapezoidal defect in IVD were weighed, and the production of trapezoidal defect in IVD was evaluated. Results The lumbar intervertebral space height of ovine was (4.45±0.28) mm. There were significant differences in the thickness of AF (4.08±0.50) mm , thickness (3 mm) and height (5 mm) of trapezoidal defect (P < 0.05), respectively. There were no significant differences in trapezoidal defects in ovine lumbar IVD in vitro on the upper bottom (3.03±0.09)mm, the lower bottom (5.03±0.09) mm, the height (4.97±0.10) mm, the thickness(3.02±0.06) mm and the trapezoidal defect predetermined value on the upper bottom 3 mm, the lower bottom 5 mm, the height 5 mm and the thickness 3 mm (P > 0. 05). The weights of the AF and NP taken out from ovine lumbar IVD in vitro and in vivo were (0.162 ± 0.011) g and (0.166 ± 0.014) g, and there was no significant difference between them (P > 0.05). Conclusion Through the operation of minimally invasive lateral approach, the method of making a trapezoidal defect in the experiments can establish animal model of AF partial defect, which meets the requirements for the repairing of IVD defect, and is simple, safe and reliable. [ABSTRACT FROM AUTHOR]

Ovarian cancer has the highest motality among the female reproductive malignancies. The underling mechanism is still unknown, and the prognosis has not been improved significantly. To establish an ideal preclinical model is in favor of the study of recurrence and metastasis in ovarian cancer. Recently, the development of patient derived xenografts model gives us a new platform for preclinical study. Gradually it has been used in the study of breast cancer, lung cancer and colon cancer, where it is proved to be useful. Much less studies on the use of patient derived xenografts model in ovarian cancer has been reported and data was shown promising. Based on the existing literature retrieval, this model could better copy the biological characteristics of the primary tumor and keep the heterogeneity of primary tumor. But there were still some problems need to be solved in the application of it, such as the different tumor take rate, the limited tumor resources and the lack of effective quality control standards. Here this review aims to address the application status, existing problems and application prospects of this model. [ABSTRACT FROM AUTHOR]

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Objective: To study the hemodynamic characteristics of concealed perforator flap in mini-pigs by ultrasonic Doppler technique., Methods: Seven 7-month-old mini-pigs, weighing 20-25 kg, were included in the study. The saphenous artery perforator flap (group A, n =4), saphenous artery concealed perforator flap (group B, n =5), and saphenous artery concealed perforator flap combined with sarcolemma (group C, n =5) models were established randomly on both hind limbs of pigs. The pigs and flap survival conditions were observed after operation. The percentage of flap survival area was calculated by Photoshop CS5 software at 5 days after operation. Ultrasonic Doppler technique was performed on the flaps before operation and at immediate, 3 days, and 5 days after operation to record the hemodynamic changes of the flaps. The hemodynamic indicators of saphenous artery (inner diameter, peak systoli velocity, resistance index, and blood flow) and saphenous vein (inner diameter, maximum velocity, and blood flow) were recorded., Results: At 1 day after operation, 1 pig died of infection, and the rest survived until the experiment was completed. Finally, the 3 flaps of group A, 4 of group B, and 5 of group C were included in the study. The flaps of the 3 groups all showed swelling after operation, which was most significant at 3 days. At 3 days after operation, the flaps in group B showed partial bruising and necrosis. At 5 days after operation, the flaps in groups A and C were basically alive, and the necrosis area of flap in group B increased further. The percentage of flap survival area in groups A, B, and C were 99.7%±0.5%, 74.8%±26.4%, and 100%, respectively. The percentage of flap was significantly lower in group B than in groups A and C (P <0.05). There was no significant difference between groups A and C ( P >0.05). There were significant differences in the hemodynamic indicators of saphenous artery and vein between different time points in 3 groups ( P <0.05). There was no significant difference in each indicator between groups at each time point ( P >0.05)., Conclusion: Both the saphenous artery concealed perforator flap and the flap combined with sarcolemma have stable blood flow, but the survival area of the latter was better than the former.

Hepatitis B virus (HBV) infection is the main cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma, and it is also a major health problem around the world. How to establish an efficient, reliable, and standardized animal model of chronic HBV infection is essential to the study of the pathogenesis and prevention strategies for HBV infection. This review summarizes the general research and new advances in using tree shrews as the model of HBV infection. We believe that tree shrews, as lower primates, will provide a vital platform and have a huge potential for building a proper animal model in the future, and could become the essential animal model for simulating the process of HBV infection in humans. [ABSTRACT FROM AUTHOR]