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This study analyzed the advantages and disadvantages of existing animal models in China and abroad and their goodness of fit based on the clinical characteristics and diagnostic criteria of stable chronic obstructive pulmonary disease(COPD) in traditional Chinese medicine(TCM) and western medicine, followed by the collation and summarization of model evaluation methodologies. The results showed that the existing animal models of stable COPD were mainly modeled via smoke exposure or the combination of multiple methods like smoke exposure plus lipopolysaccharide or protease or bacterial infection. These animal models generally failed to simulate the clinical characteristics of TCM, and their goodness of fit in western medicine was higher than that in TCM. There is a lack of research on the animal models of stable COPD and the disease-syndrome combination models. Although the modeling is guided by the pathogenesis or mechanism of diseased humans, the established models were still not identical with the actual clinical situations. In-depth research is needed to develop quantitative standards for stable COPD models.

Based on the clinical characteristics of atopic dermatitis( AD) in traditional Chinese medicine( TCM) and Western medicine,the existing animal models were analyzed,and the coincidence degree,advantages and disadvantages between the models and the clinical manifestations of AD were evaluated,so as to provide reference for establishing a rational animal model. After consulting relevant literatures in recent years and summarizing the existing modeling methods,it is found that spontaneous,transgenic/gene knockout models were highly consistent,but with high breeding conditions and expensive prices. The hapten-induced model was low in cost and fast in modeling. It revealed the corresponding mechanism of AD to a certain extent,but did not fully reflect the state of the entire process of AD. The modeling method was guided by Western medicine,but with a lack of pathogenic factors of traditional Chinese medicine,and so has certain limitations in TCM research. Therefore,it is necessary to combine the etiology,pathogenesis and clinical mani-festations of AD with traditional Chinese and Western medicine,so as to improve the coincidence degree between the model and the characteristics of clinical symptoms and lay the foundation for in-depth studies on AD.

Based on the characteristics of clinical symptoms of chronic skin ulcers in traditional Chinese and Western medicine, the current animal models of skin ulcers are summarized. This article analyzes the advantages and disadvantages of animal models according to the etiology and pathogenesis of chronic skin ulcers, traditional Chinese and Western medicine diagnostic criteria and observation indicators, and eva-luates the agreement between the existing animal models and the characteristics of clinical syndromes of traditional Chinese and Western medicine for chronic skin ulcers. Through analysis and comparison, it is found that most of the existing modeling methods are single-factor animal models, and there are certain gaps in the physiological and pathological characteristics of chronic skin ulcers caused by clinical multi-factors and interactions. Most of the modeling methods are guided by Western medicine. The lack of pathogenic factors of traditional Chinese medicine(TCM) in the process of modeling. Therefore, this article proposes to establish a reasonable quantification standard for chronic skin ulcer animal models, and to establish a combination model of chronic skin ulcer disease with traditional Chinese and Western medicine as the focus of future animal model research.

This article aims to provide a good experimental method for the study of drug treatment of ulcerative colitis. According to the characteristics of ulcerative colitis's clinical symptoms, common ulcerative colitis animal models were analyzed. Based on the characteristics of clinical symptoms of traditional Chinese medicine and Western medicine for ulcerative colitis disease, the existing commonly used animal models of ulcerative colitis were analyzed to summarize the current matching degree, advantages and disadvantages of the exi-sting animal models of ulcerative colitis and clinical symptoms. At present, studies on ulcerative colitis mainly adopt four types of induction modeling methods, such as immunization, chemical stimulation, compound method and gene model. There are many reported methods of colitis modeling, but no model can reflect the characteristics of clinical symptoms of ulcerative colitis treated with Western or Chinese medicine. This article summarizes the characteristics, clinically relevant symptoms and applicable scope of immunization, chemical stimulation, compound method, and gene model, so as to provide a reliable animal model for subsequent studies of prevention and treatment of colitis.

The evaluation standard of LEAD animal model was established according to the understanding of the etiology and pathogenesis of diabetic lower extremity vascular disease based on Chinese and Western medicine. The consistency between the existing LEAD animal model and the clinical characteristics of traditional Chinese and Western medicine was analyzed and evaluated. The advantages and disadvantages of the existing model were compared,the application scope of different models was considered,and the possible improvement methods of the existing model were proposed,so as to provide impetus for the improvement of LEAD animal model.We should reflect more characteristics of traditional Chinese medicine syndromes in the process of model improvement and development,making the LEAD animal model to get closer to clinical features of traditional Chinese and Western medicine.

The incidence of heart failure has increased year by year, with a negative impact on quality of life and life expectancy of patients. Reproduction of animal models that meet the characteristics of clinical symptoms is a prerequisite for conducting experimental studies relating to heart failure. Based on the characteristics of clinical symptoms of heart failure in traditional Chinese medicine(TCM) and Western medicine, the existing common animal models of heart failure were explored, and the clinical anastomosis of the existing animal models was analyzed based on the clinical diagnostic criteria of heart failure in TCM and Western medicine. After analysis and comparison, it can be seen that the existing modeling methods are mostly single-factor animal models, with certain gaps between the characteristics of clinical multi-factors and interactions that jointly lead to heart failure, and the modeling methods were mostly guided by Western medicine, with a lack of TCM pathogenic factors in the model process, which is different from the clinical diagnostic criteria of Chinese and Western medicine for heart failure. In terms of syndrome differentiation, heart failure is classified into heart and lung Qi deficiency syndrome, Qi and Yin deficiency syndrome, heart and kidney Yang deficiency syndrome, Qi deficiency and blood stasis syndrome, Yang deficiency and water flooding syndrome, phlegm-drinking obstructive lung syndrome, Yin and yang exhausted syndrome. The existing animal models mostly confused them, with no effective and recognized method for modeling at present. There are major limitations in studies of Chinese medicine. Therefore, based on clinical characteristics of heart failure in Chinese and Western medicine, this article analyzed the existing animal models, defined their advantages and disadvantages and application prospects, and then suggested further improving the corresponding animal models of heart failure and standardizing the model evaluation, so as to improve the clinical coincidence between animal models and Chinese and Western medicine, make heart failure animal models better serve scientific studies, and promote relevant mechanism studies, pathological change studies and drug screening.

Based on the clinical characteristics of chronic atrophic gastritis in traditional Chinese and Western medicine, the domestic and foreign relevant literature reports and animal models of chronic atrophic as well as the clinical diagnostic indicators of traditional Chinese and western medicine, chronic atrophic gastritis evaluation standard was summarized to evaluate and analyze the coincidence degree of clinical symptoms of the existing chronic atrophic gastritis animal models. The statistical results found that modeling methods with a higher coincidence degree with the existing chronic atrophic gastritis animal models are disease and syndrome combination mode-ling, surgical modeling, multifactor comprehensive modeling and MNNG modeling. Although the animal models were reproduced by such methods as etiology, pathogenesis and disease and syndrome combination similar to those of human beings, there is still a big gap with the natural disease state. Further in-depth studies and improvement shall be made in clinical practice in the hope to provide refe-rence for clinical practice and experimental studies of chronic atrophic gastritis.

Based on the characteristics of clinical symptoms of secretory otitis media in traditional Chinese and Western medicine,by reference to clinical diagnostic criteria,efforts were made to analyze and establish the Western medical diagnostic criteria and traditional Chinese medicine( TCM) syndrome differentiation criteria for secretory otitis media,and summarize the modeling methods and model characteristics of secretory otitis media animal models. According to the clinical diagnostic criteria and symptom characteristics,the coincidence degree between the existing animal models and clinical symptoms was evaluated,and its advantages and disadvantages were defined. On the basis of the statistical results,there were fewer methods for modeling secretory otitis media animal models,and only a specific relevant pathogenic mechanism could be revealed. Among them,the model with a higher coincidence degree was genetic engineering technology modeling and injection into the middle ear vesicles. The two modeling methods of bacterial factors highly coincided with the clinical symptoms of Western medicine,but both failed to reflect the TCM syndrome type. Therefore,establishing an animal model that simultaneously reflects the characteristics of clinical symptoms of secretory otitis media in traditional Chinese and Western medicine,and improving the evaluation criteria of secretory otitis media based on animal models are the main tasks of future studies on secretory otitis media.

Abstract This study aims to establish an animal model of monkeypox virus (MPXV) infection in dormice through intranasal inoculation. Male dormice aged 4–5 months were selected as experimental subjects and administered different titers of MPXV (103.5 PFU, 104.5 PFU, and 105.5 PFU, respectively) via nasal instillation. Within 14 days post-infection, clinical indicators such as survival rate, body weight changes, respiratory status, and mental state were continuously monitored. Additionally, tissue samples from the lungs, liver, spleen, and trachea of dormice from each group were collected on the 5th and 10th days for virus titer detection, and histopathological analysis was performed on lung samples collected on the 5th and 10th days. Dormice infected with MPXV exhibited typical symptoms such as appetite loss, continuous body weight reduction, aggravated respiratory difficulties, accompanied by lethargy, chills, and other clinical manifestations similar to human monkeypox infection. Virological tests further confirmed the distribution of MPXV in multiple vital organs of dormice, including the lungs, liver, spleen, and trachea, with particularly significant pathological damage observed in lung tissue. An MPXV infection model in dormice was successfully established through intranasal inoculation with a titer of 105.5 PFU MPXV, which can be used for studying the infection mechanism and pharmacology of MPXV.

Abstract Urinary tract injuries represent a significant clinical challenge, necessitating precise diagnosis and effective treatment strategies. Rat models are preferred for studying urinary tract injuries due to their size, visibility of external genitalia, and robust reproductive and growth capabilities. However, there is a lack of standardized methodologies for evaluating the endpoints of rat urinary tract injury models. This study aimed to investigate the methodology of model establishment, imaging evaluation techniques, and endpoint effectiveness. Twenty-four male Sprague-Dawley rats were randomly assigned to groups, including a blank control group and surgical groups. The surgical groups underwent urethral injury induced by recombinant transforming growth factor-β1 (TGF-β1) solution, followed by the random selection of one surgical group (n = 6) to receive treatment with mesenchymal stem cell (MSC) exosomes. High-frequency ultrasonography using a GE E10 device combined with a water bath method was employed to evaluate the urethral conditions of all rats. Ultrasonographic characteristics were scored for all surgical group rats, and an intergroup analysis was conducted between the surgical group and the control group rats. Statistical analysis was conducted using SPSS 22.0 software. Ultrasonographic assessment revealed significant differences in urethral echogenicity between the normal group and the surgical group, with noticeable changes in urethral morphology post-injury. Histopathological examination confirmed more severe urethral stenosis in the TGF group compared to the MSC group. High-frequency ultrasound could effectively differentiate between the two groups of rats. Additionally, there were significant differences in the scoring of ultrasonographic characteristics between the two groups. Urethral stricture presents a complex challenge in urology, often requiring invasive treatment modalities. The establishment of animal models plays a crucial role in understanding and addressing this condition. TGF-β1 induced fibrosis and MSC therapy represent promising avenues for urethral stricture management. High-frequency ultrasound combined with the immersion method offers a non-invasive and cost-effective approach for evaluating rat urethral stricture models. This study highlights the practicality of high-frequency ultrasound combined with the water bath method in evaluating rat urethral stricture models, as it can effectively differentiate between rats in the pure TGF-β1 induced group and those in the MSC treatment group based on urethral changes. The results underscore the importance of standardized methodologies for model assessment and the potential of non-invasive imaging techniques in preclinical research. Overall, this study contributes to advancing our understanding of urinary system injuries and holds implications for future therapeutic interventions in urology.

Abstract Traditional mouse models for deep vein thrombosis (DVT), frequently utilized in research focused on cancer-associated thrombosis (CAT), reliably induce thrombus formation by obstructing blood flow (BF) in the inferior vena cava (IVC), which does not occur in humans. Therefore, to develop a new DVT model for CAT studies, we implanted an ameroid constrictor (AC), a hygroscopic casein C-shape device, around the IVC and aorta of immunocompromised mice. We evaluated the thrombus 3 and 8 days post-AC implantation and compared it with the traditional model 2 days post-vena cava ligation. The size of each thrombus was measured, and the composition was assessed using histological staining; BF through the IVC was confirmed using ultrasound imaging. The thrombus size variability in the AC and ligation models was equivalent. Compared with thrombi on day 3 post-AC implantation, those on day 8 showed characteristics of human thrombi in the subacute to chronic stage. The BF in the IVC was maintained even on day 8. In summary, the AC model showed reproducibility with no significant difference in thrombus size variability from the traditional ligation model while maintaining the BF of the IVC.

Abstract Trimethyltin chloride (TMT), an organotin compound with potent neurotoxicity, is widely used as a heat stabilizer for plastics. However, the precise pathogenic mechanism of TMT remains incompletely elucidated, and there persists a dearth of sensitive detection methodologies for early diagnosis of TMT. In this study, Sprague-Dawley rats were treated with 10 mg/kg TMT to simulate acute exposure in humans. Micro-positron emission tomography/computed tomography (Micro-PET/CT) and molecular imaging quantitative analysis tools were employed to calculate the uptake rate of 18 F-2-fluoro-D-deoxy-glucose in each functional region of brain tissue. At the same time, the neurobehavioral test and neuropathological results of the experimental rats were compared, aiming to assess the feasibility of PET/CT in the detection and localization of TMT nervous system damage from many aspects. The results showed that TMT decreased glucose uptake in a wide range of brain tissues in rats, and impaired the memory, muscle strength, coordination ability and emotion of rats. Moreover, TMT induced neuronal damage within the cerebral cortex, hippocampal CA1, CA3 and DG regions as well as the cerebellum while also promoting gliosis surrounding the hippocampus. PET/CT imaging results are highly consistent with behavioral and pathological results. In conclusion, TMT induces a widespread reduction in energy metabolism across various brain regions, and PET/CT can serve as a sensitive detection method for TMT-induced encephalopathy.

Animal models are valuable tools for studying the underlying mechanisms of and potential treatments for intervertebral disc diseases. In this review, we discuss the advantages and limitations of animal models of disc diseases, focusing on lumbar spinal stenosis, disc herniation, and degeneration, as well as future research directions. The advantages of animal models are that they enable controlled experiments, long-term monitoring to study the natural history of the disease, and the testing of potential treatments. However, they also have limitations, including species differences, ethical concerns, a lack of standardized protocols, and short lifespans. Therefore, ongoing research focuses on improving animal model standardization and incorporating advanced imaging and noninvasive techniques, genetic models, and biomechanical analyses to overcome these limitations. These future directions hold potential for improving our understanding of the underlying mechanisms of disc diseases and for developing new treatments. Overall, although animal models can provide valuable insights into pathophysiology and potential treatments for disc diseases, their limitations should be carefully considered when interpreting findings from animal studies.

Abstract Mutations in the gene ABCA4 coding for photoreceptor-specific ATP-binding cassette subfamily A member 4, are responsible for Stargardts Disease type 1 (STGD1), the most common form of inherited macular degeneration. STGD1 typically declares early in life and leads to severe visual handicap. Abca4 gene-deletion mouse models of STGD1 accumulate lipofuscin, a hallmark of the disease, but unlike the human disease show no or only moderate structural changes and no functional decline. The human macula is highly enriched in cones, and reasoning that the low cone percentage in mice retinas ( 30% cones. Compared to control injections of AAV-abca4-GFP, treated eyes exhibited extensive retinal degeneration by two months. Sanger sequencing of the CRISPR targeted sequence show a clear edition of Abca4 gene. Non-invasive fundus imaging showed widespread photoreceptor loss, confirmed by ocular coherence tomography. Functional recording by single flash and flicker electroretinography showed significant decline in photopic (cone) light responses. Post-mortem real-time PCR, immunohistochemistry and western blotting showed significant decrease of cone-specific (MW cone opsin) but not rod-specific (rhodopsin) markers. Transmission electron microscopy showed large numbers of lipid inclusions in treated but not control retinal pigmented epithelium. Finally, ultra-high performance liquid chromatography analysis of whole P. obesus eyes showed the presence of all-trans retinal-dimer, not detected in rod-rich rat eyes. In conclusion, Abca4 knockout in P. obesus results in a predominantly cone degeneration phenotype, more accurately reflecting the etiology of human STGD1, and should be valuable for characterizing pathogenic pathways and exploring treatment options.

Abstract Hydrocephalus commonly occurs after subarachnoid hemorrhage (SAH) and is associated with increased morbidity and disability in patients with SAH. Choroid plexus cerebrospinal fluid (CSF) hypersecretion, obliterative arachnoiditis occluding the arachnoid villi, lymphatic obstruction, subarachnoid fibrosis, and glymphatic system injury are considered the main pathological mechanisms of hydrocephalus after SAH. Although the mechanisms of hydrocephalus after SAH are increasingly being revealed, the clinical prognosis of SAH still has not improved significantly. Further research on SAH is needed to reveal the underlying mechanisms of hydrocephalus and develop translatable therapies. A model that can stably mimic the histopathological and neuroethological features of hydrocephalus is critical for animal experiments. There have been fewer animal studies on hydrocephalus after SAH than on other stroke subtypes. The development of a reproducible and effective model of hydrocephalus after SAH is essential. In this study, we establish a mouse model of SAH that stably mimics brain injury and hydrocephalus after SAH through injections of autologous blood into the cisterna magna via different methods and characterize the model in terms of neurological behavior, histology, imaging, neuronal damage, and white matter damage.

ObjectiveTo establish a rat model of moderate-to-severe knee osteoarthritis, laying the foundation for studying the pathogenesis of moderate-to-severe knee osteoarthritis and its prevention and treatment methods.MethodsThirty male SD rats were randomly divided into three groups: a sham surgery group, an 8-week model group, and a 20-week model group, with 10 rats in each group. Rats in the 8-week and 20-week model groups underwent surgery to cut the anterior and posterior cruciate ligaments and medial collateral ligament of the right knee joint, and remove the medial and lateral menisci. After surgery, the rats were allowed to move freely. The rats in the sham surgery group had only skin incisions to expose the joint without any surgical treatment. At 8 and 20 weeks post-surgery, Micro-CT scans were performed to analyze the femoral osteoporosis in the rats. After euthanizing the rats, gross observations of the knee joints were made, and the cartilage of the joint surface was scored using the Pelletier scoring system. The knee joints were collected for hematoxylin and eosin (HE) staining and safranin O-fast green staining to observe changes in cartilage morphology. The modified Mankin's scoring system was used to assess the tissue pathology of the joint surface. Immunohistochemical staining was used to detect the expression of type II collagen and matrix metalloproteinase 13 (MMP13), reflecting the anabolic and catabolic metabolism of the knee joint cartilage.ResultsThe knee joint cartilage in the 8-week and 20-week model groups was severely damaged, with Pelletier and modified Mankin's scores significantly higher than those in the sham surgery group (both P

Atmospheric fine particulate matter (particulate matter 2.5,PM2.5) is a major component of haze, and its potential hazards to human reproductive health have garnered widespread attention. Establishing appropriate animal models is crucial for in-depth research into the reproductive toxicity of PM2.5 exposure and its underlying mechanisms. This paper, based on recent literature, summarizes current methods for establishing PM2.5-exposed animal models and the evaluation criteria for reproductive toxicity research. The primary modeling methods for PM2.5 exposure include whole-body inhalation exposure and intratracheal instillation exposure. While whole-body inhalation exposure effectively simulates real-life human inhalation environments, it requires sophisticated experimental equipment. Conversely, intratracheal instillation exposure is more cost-effective and easier to operate but faces challenges in accurately mimicking the distribution and deposition of PM2.5 during natural inhalation. Therefore, researchers must carefully weigh these exposure methods to enhance model rigor and achieve the most realistic simulation of human exposure conditions. When summarizing the application evaluation indicators of PM2.5-induced reproductive toxicity, this review finds that the main indicators of male reproductive toxicity include reduced sperm quality, testicular tissue damage, and hormonal imbalances. For female reproductive toxicity, the primary indicators are reduced ovarian reserve, endocrine dysfunction, endometrial damage, and adverse perinatal reactions. Additionally, this review highlights the need for detailed chemical composition analysis of PM2.5, exploring the reproductive toxic targets and mechanisms of particles containing different chemical components, such as heavy metals and polycyclic aromatic hydrocarbons. Long-term studies are also necessary to assess the effects of PM2.5 exposure on reproductive health and transgenerational effects, to predict potential long-term risks for humans. Additionally, interdisciplinary collaboration should be encouraged, involving cooperation between environmental science, toxicology, reproductive medicine, and other disciplines, to comprehensively assess the environmental health risks of PM2.5 and provide scientific support for the development of integrated prevention and control strategies. This review summarizes animal modeling methods, evaluation criteria, and their applications, providing valuable methodological references for future reproductive toxicity research on PM2.5.

Objective This study aims to establish a novel hyperglycemic obesity mouse model by utilizing Triacsin C, an inhibitor of acyl-CoA synthetase long-chain family member 1 (ACSL1), combined with a high-fat diet, to simulate the changes in adipose tissue and cardiac function observed in patients with obesity-related type 2 diabetes.MethodsTwenty adult SPF-grade male C57BL/6J mice were randomly divided into two groups: the Control group (injected intraperitoneally with citric acid-sodium citrate buffer, Con group) and the TC group (injected intraperitoneally with Triacsin C, TC group). After four consecutive weeks of intraperitoneal injections, both groups were fed high-fat diets. Body weight and glucose tolerance of the mice were assessed every eight weeks. The models were considered successful if fasting blood glucose exceeded 8 mmol/L or blood glucose was above 15 mmol/L two hours after glucose injection. Cardiac function, including ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), end-diastolic interventricular septal thickness (EDIVS), left ventricular ejection fraction (LVEF), and left ventricular short-axis fractional shortening (FS), was measured by echocardiography. HE staining was used to detect the changes in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT). Immunofluorescence technology was used to analyze changes in CD31 and UCP1 in BAT. ACSL1 expression in myocardial tissue was tested by Western blotting.ResultsThe fasting blood glucose levels were (8.14±1.43) mmol/L in the Con group and (8.18±0.85) mmol/L in the TC group (P>0.05) , and the 2-hour postprandial blood glucose levels were (19.8±4.01) mmol/L in the Con group and (22.60±3.97) mmol/L in the TC group (P

Objective To investigate the effect of resveratrol (RSV) in the treatment of peri-implantitis in a murine model and its effect on nuclear factor kappa-B (NF-κB) signaling and mitogen-activated protein kinase (MAPKs) signaling. Methods This study has been reviewed and approved by the Ethics. After extracting the right maxillary molars of 40 C57BL/6 mice and allowing them to heal naturally for 8 weeks, implants were implanted at the site of the first molar. The mice were randomly divided into a control group, a mouse peri implantitis model group, a low-dose group of 20 mg/kg resveratrol (RSV-L), and a high-dose group of 40 mg/kg resveratrol (RSV-H). After 4 weeks of implant implantation, a silk thread ligation induced peri implantitis model was established in all mice except for the control group. The model group received intervention with physiological saline by gavage, while the drug group received intervention with resveratrol by gavage for 6 consecutive weeks. After 6-week treatment, observe the swelling of the gums around the implant and measure the bone resorption around the mouse implant using micro CT. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in gingival crevicular fluid. HE staining was used to observe the infiltration of inflammatory cells in the surrounding tissues of mouse implants. Protein expression level and phosphorylation level of extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen activated protein kinase (p38 MAPK), p-p38MAPK, nuclear factor kappa-B (NF-κB), p-NF-κB, nuclear factor-κB inhibitory protein (IκΒα), p-IκBα in MAPKs/NF-κB signaling pathway were detected by Western blot (WB). Results Resveratrol group showed reduced tissue edema and decreased alveolar bone resorption. Among them, the high-dose resveratrol group had lighter tissue edema and weaker bone resorption compared to the low-dose group. The micro CT results showed that significant changes in the bone level around the implant were observed in the model group mice at four sites: proximal, distal, buccal, and palatal. High dose resveratrol intervention reduced alveolar bone resorption (PPP>0.05). The ELISA results showed that compared with the model group, the levels of TNF - α and IL-6 in the gingival crevicular fluid of mice in the low-dose and high-dose resveratrol groups were lower (PPPP

Abstract Ectopic pregnancy affects ~ 2% of pregnancies annually in the United States, with no current treatments allowing for the continuation of the pregnancy. Thus, this study sought to initiate an investigation into the potential design of a surgical technique, in an animal model, that could serve as a foundation for future research into the potential of relocating an ectopic embryo into the uterus at the human level. Female Long-Evans rats were randomly assigned to one of two groups: Embryo Relocation (ER; n = 12; underwent embryo relocation surgery) and Normal Pregnancy (NP; n = 12; carried a normal pregnancy; no surgery). Eight rats/group were allowed to carry their pregnancy to term and deliver, while four had their uteri collected at the end of gestation. Briefly, for the ER group, a uterine horn containing 1–2 embryos was translocated to the contralateral horn, which had been incised and cleared of its contents, prior to being wrapped around the relocated horn. Rat weight, food consumption and vaginal impedance of the mothers were measured throughout the experiment. Ultrasounds were performed and fetal heart rates measured on day 20–21 of gestation. Additionally, rat weight of all offspring was measured at adulthood. Our findings indicate that, in the ER group, 15/15 (100%) of the relocated embryos had detectable heart rates at the end of gestation (within the normal range), 14/15 (93%) were delivered vaginally, and 12/14 (86%) survived until adulthood. A significant decrease in rat weight and food consumption was observed only on the day following surgery. Fertility, as measured by vaginal impedance, was minimally impacted by surgery. Moreover, there was no significant difference between groups in average body weight of offspring at adulthood. Histological analysis indicated a thicker placenta in the ER group, attributable to the fetal part of the placenta, potentially indicating compensatory mechanisms. Our findings reflect a successful transuterine embryo relocation followed by vaginal birth and survival of offspring to adulthood, in a rat model. Such findings lay the foundation for future preclinical research in higher animals, with potential implications on a procedure relevant to human ectopic embryo relocation.

Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P

Exploration of the underlying mechanisms of tumor occurrence and development, as well as evaluation of the efficacy of anticancer drug treatments, relies on various research models both in vivo and in vitro. Over the past few decades, with the rapid advancement of biomedical technology, significant achievements have been made in this field. Gene detection technology has progressed from a single-gene perspective to multi-gene approaches, resulting in rapid development of bioinformatics and transformation of the conceptual understanding of malignant tumors. Moreover, in vitro cell research models have evolved from monolayer two-dimensional and primary cultures to three-dimensional configurations, which better imitate the cellular interactions and functions within tumor tissues. Furthermore, in vivo animal research models have transitioned from traditional carcinogen induction and cell or tissue xenografts to genetically engineered animal models or xenograft models, enabling targeted investigation into the roles of relevant genes in the occurrence and development of tumors. Clinical research has shifted from simple retrospective to prospective studies, including phase Ⅰ/Ⅱ/Ⅲ clinical trials, investigator-initiated clinical trials, and real-world clinical trials. The major shortcomings of current malignant tumor research models include their singularity, insufficient simulation of the tumor microenvironment, disparities between animal models and human tumors, and the lack of consideration for personalized medicine. Further research and optimization of the models are still needed in the future, along with more effective integration of different models to form an optimized comprehensive experimental model system. This review systematically examines and comprehensively overviews the evolution of malignant tumor research models with the aim of providing more references to researchers engaged in oncology research.

Abstract Endoscopic ultrasound-guided fine needle biopsy is an effective method for obtaining tissue samples from various organs; however, challenges such as inadequate specimens persist. This study compared a newly designed Tricore needle with a Franseen needle for endoscopic ultrasound-guided fine needle biopsy of porcine liver. Both needles were tested on four male Yorkshire pigs. Specimens were obtained with an 100% (36/36) success rate with no procedure-related adverse effects. The Tricore needle experienced significantly less resistance during puncture than Franseen needle (3.83 vs. 5.97 N, P

Objective·To establish a mouse model with dormant cancer and no obvious metastasis by combining the preimmune strategy with the mVenus-p27K－ cell G0 phase indicator system, the DTR-HSV/TK suicide gene system, and the Luc2-tdTomato tracer system.Methods·The KPC1199 mouse pancreatic cancer cell line was transfected with the mVenus-p27K－ cell G0 phase indicator system, the DTR-HSV/TK suicide gene system, and the Luc2-tdTomato tracer system to construct a stable expression cell line, KPC1199-PDL. After being cultured in the serum-free condition, KPC1199-PDL cells were sorted into mVenus (+) cells and mVenus (-) cells by flow cytometry, and the expression of G0 phase-related genes was verified by real-time fluorescence quantitative PCR (qPCR). Sensitivity of KPC1199-PDL cells to diphtheria toxin (DTX) and ganciclovir (GCV) was evaluated by CCK-8 assay. A transsplenic portal vein-hepatic metastasis model was constructed in wild-type C57BL/6 mice to validate the function of KPC1199-PDL cells in vivo by immunofluorescence technology. The KPC1199-PDL cells were injected subcutaneously into C57BL/6 mice, followed by in situ injection of DTX and GCV to ablate subcutaneous tumors 5 d later, to obtain preimmunized mice. The transsplenic portal vein-hepatic metastasis models were constructed in these mice. Bioluminescence imaging was used to evaluate subcutaneous tumor ablation and hepatic metastasis in the mice, and immunofluorescence assay was used to detect the distribution and dormant state of tumor cells in the livers of preimmunize mice.Results·The three tool systems were stably expressed in KPC1199-PDL cells, and their proliferative ability was not affected. In the serum starving condition, some KPC1199-PDL cells expressed the mVenus protein, indicating entry into the G0 phase; the mVenus (+) cells sorted out by flow cytometry exhibited significantly higher expression of G0 phase-related genes (all P

Objective The purpose of this study was to investigate the timing and mode of failure of metallic screw-type suture anchors used to attach artificial tendons to bone in an in vivo New Zealand White rabbit model. Study Design Metal suture anchors with braided composite sutures of varying sizes (United States Pharmacopeia (USP) size 1, 2, or 5) were used to secure artificial tendons replacing both the Achilles and tibialis cranialis tendons in 12 female New Zealand White rabbits. Artificial tendons were implanted either at the time of (immediate replacement, n = 8), or four/five weeks after (delayed replacement, n = 4) resection of the biological tendon. Hindlimb radiographs of the rabbits were obtained immediately after surgery and approximately every other week until the study endpoint (16 weeks post-surgery). Results All suture anchors used for the tibialis cranialis artificial tendons remained secure and did not fail during the study. The suture anchor used to attach the Achilles artificial tendon to the calcaneus bone failed in nine of 12 rabbits. In all cases of suture anchor failure, the suture broke away from the knot, while the metallic screw remained securely embedded in the bone. Based on radiographic analysis, the mean estimated failure timepoint was 5.3 ± 2.3 weeks post-surgery, with a range of 2–10 weeks. Statistical analyses (Mann–Whitney U test and Fisher’s exact test) revealed no significant effect of tendon implantation timing or suture size on either the timing or frequency of suture anchor failure. Conclusion For the suture anchors used to attach artificial tendons in this study, suture anchor failure was most likely due to suture wear or cutting against the eyelet of the anchor screw. Future studies are needed to test the effect of suture-eyelet interaction on suture strength under different loading conditions.

Objectives: Epilepsy is a disease with vast complexity and diverse clinical manifestations causing neuronal misfiring. Diospyros mespiliformis (DM) possesses anti-epileptic properties. Methods: Fifty rats were used for this study. Group A received normal saline while groups B, C, D, and E received lithium chloride (127 mg/kg, i.p.) + pilocarpine (30 mg/kg, i.p.) to induce seizure. Following induction, C, D, and E received 50 mg/kg, 200 mg/kg DM and 10 mg/kg sodium valproate respectively (p.o) while B was left untreated. Rats were assessed for Open field and radial arm maze tests. Levels of SOD, MDA, catalase glutamate, GABA, IL-6 and TNF-alpha were assayed using appropriate protocols. Histological and immunohistochemistry tests were done. Results: DM reduced glutamate levels in C, D and E when compared with A and B while there were no significant changes in the levels of GABA across groups. DM significantly reduced IL-6 in C, D and E but not in A and B while there were no significant changes in TNF alpha across groups. DM boosted catalase release than superoxide dismutase to the after-status epilepticus. In the open field test, DM reversed the altered activities in the epileptic rats. DM ameliorates neuronal vacuolation, disorientation and increased reactive gliosis. There was positive NeuN reactivity across groups except in D. Conclusion: We concluded that DM (probably 1,2,3-Benzenetriol content) can be employed in managing epilepsy as evident in the mitigation of histoarchitecture and the maintenance of the levels of the neurotransmitters.

Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features fibrotic adhesions caused by periodic bleeding. The characteristic ectopic lesions are marked by a widely spread dense fibrotic interstitium comprising of fibroblasts, myofibroblasts, collagen fibers, extracellular proteins, inflammatory cells, and active angiogenesis. Fibrosis is now recognized as a critical component of endometriosis because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or noncyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root causes, etiology, and complex pathogenesis of this debilitating condition, hinders early diagnosis and implement effective therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Emerging research offer a close relationship between endometriosis and fibrosis, which is believed to be tightly linked to pain, a primary contributor to the deterioration of the patient’s quality of life. However, the underlying pathophysiological cellular and molecular signaling pathways behind endometriosis-associated fibrosis are poorly addressed. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease limiting the treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article focuses on recent developments in the field and highlight the necessity for novel fibrotic models for early diagnosis, a better understanding the disease’s etiology and develop effective anti-fibrotic treatments. By addressing these knowledge gaps, we want to open fresh avenues for a thorough investigation and extended research in the field of endometriosis.

Abstract To study a new method for establishing animal models of prenatal bronchopulmonary dysplasia (BPD), we used lung ultrasound score (LUS) to semi-quantitatively assess the severity of lung lesions in model rats. Lipopolysaccharide (LPS) was injected into the right lung of the fetus of the rat under ultrasound-guided, and the right lung of the neonates were scanning for LUS. Specimens were collected for pathological scoring and detection of pulmonary surfactant-associated glycoprotein (SP)-C and vascular endothelial growth factor (VEGF) expression quantity. The correlation between LUS and pathological scores was analyzed. (1) The animal models were consistent with the pathological manifestations of BPD. (2) It showed a strong positive correlation between LUS and pathological scores in animal models (r = 0.84, P

Abstract Pulmonary arterial hypertension (PAH) is a well-known complication of congenital heart disease (CHD). The lack of a satisfactory animal model for PAH associated with CHD (PAH-CHD) has limited progress in understanding the pathogenesis of PAH and the development of therapeutic agents. The development of a rat model for PAH associated with atrial septal defect (ASD) was achieved through atrial septal puncture and thermal ablation. Two and 4 weeks after modeling, hematoxylin and eosin staining showed that the vascular thickness, vascular thickness index, vascular area, and vascular area index in pulmonary arteries with an outer diameter of 50–300 μm in the PAH-ASD 2 and 4 weeks group were higher than those in the sham group (all P

Abstract Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan.

Objective To summarize and evaluate the characteristics of current recurrent spontaneous abortion (RSA) animal models at home and abroad, and to provide reference and guidance for the standardized preparation of RSA models.Methods"Recurrent spontaneous abortion" and "animal model" were used as co-keywords in CNKI, Wanfang, VIP, PubMed and Web of Science databases to search the RSA animal experimental literature, covering the period up to January 20, 2024, and a total of 1 411 articles were collected. The analysis focused on construction methods and essential elements of RSA animal models, the modeling process and result evaluation, as well as the application of these models in pharmacological and pharmacodynamic research. An Excel table was established for systematic analysis and discussion. Results A total of 138 experimental studies were obtained after screening. In constructing RSA animal models, immunological models were the most widely used in Western medicine (96.92%), with the Clark model being the main one (92.31%). In traditional Chinese medicine (TCM) models, 70.00% were kidney deficiency-luteal inhibition-syndrome combination models, 20.00% were kidney deficiency and blood stasis models, and 10.00% were deficiency-heat syndrome models. Most animals were selected at 6-8 weeks (33.86%) and 8 weeks (32.28%) of age. The majority of animals were paired for mating at 18:00 on the day of cage pairing. In 81.03% of literatures, vaginal plugs were checked once the following morning, with 8:00 being the most common time (17.02%). The most commonly used drug administration cycle was 14 days of continuous gavage after pregnancy. Among the tested drugs, Western drugs were mainly protein-based (29.17%), while TCM drugs were mainly TCM decoction (81.11%). The most frequently used methods for detecting indicators included visual observation of embryos (22.54%), western blot (15.96%), PCR (13.58%), ELISA (12.91%), HE staining (10.80%) and immunohistochemistry (9.39%). Conclusion The etiology of RSA is complex, and corresponding animal models should be established based on different etiologies. Clark model is commonly used in the construction of Western medicine model, while the kidney deficiency-luteal inhibition-syndrome combination model is predominant in TCM. RSA animal model is widely used in related research, but systematic evaluation needs to be strengthened.

Abstract Dysbindin-1, a protein encoded by the schizophrenia susceptibility gene DTNBP1, is reduced in the hippocampus of schizophrenia patients. It is expressed in various cellular populations of the brain and implicated in dopaminergic and glutamatergic transmission. To investigate the impact of reduced dysbindin-1 in excitatory cells on hippocampal-associated behaviors and synaptic transmission, we developed a conditional knockout mouse model with deletion of dysbindin-1 gene in CaMKIIα expressing cells. We found that dysbindin-1 reduction in CaMKII expressing cells resulted in impaired spatial and social memories, and attenuation of the effects of glutamate N-methyl-d-asparate receptor (NMDAR) antagonist MK801 on locomotor activity and prepulse inhibition of startle (PPI). Dysbindin-1 deficiency in CaMKII expressing cells also resulted in reduced protein levels of NMDAR subunit GluN1 and GluN2B. These changes were associated with increased expression of immature dendritic spines in basiliar dendrites and abnormalities in excitatory synaptic transmission in the ventral hippocampus. These results highlight the functional relevance of dysbindin-1 in excitatory cells and its implication in schizophrenia-related pathologies.

Objective This study aimed to evaluate the development of atherosclerosis in ApoE-deficient dogs fed with a high-fat diet (HFD) using vascular duplex ultrasonography (VDU). Methods Thirty beagle dogs were enrolled, including 10 wild-type, 16 heterozygous (ApoE-/+), and four homozygous (ApoE-/-) mutant dogs. The dogs were categorized into either the normal diet (ND) or HFD group. Plasma lipids levles were tested at baseline and then after feeding the dog a different diet for 6 months. The carotid arteries, abdominal aorta (AO) and iliac arteries were examined using VDU. Artery sections of the ApoE-/- dogs were analyzed. Results After HFD, lipids especially triglycerides, total cholesterol and low-density lipoprotein (LDL) in the wild type and ApoE-/+ dogs were significantly increased. Both the intima-media thickness (IMT) of the common carotid artery (CCA) and AO in the wild type and ApoE-/+ dogs significantly increased. In the ApoE-/+ dogs, the mean percentages increases in CCA-IMT and AO-IMT after HFD were higher than those in the ND dogs. The mean values of CCA-IMT and AO-IMT in the ApoE-/-dogs increased to 2-2.5 folds after HFD. Histological analysis confirmed that the carotid and iliac arteries had advanced atherosclerotic lesions in the ApoE-/- dogs. Conclusions HFD may accelerate the development of atherosclerosis in ApoE-deficient dogs, which is an optimal large-animal model of atherosclerosis.

Abstract Introduction Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2–5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients. Methods Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression. Results Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity. Conclusions Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.

Abstract Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.

Abstract Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.

Abstract The Crumbs protein (CRB) family plays a crucial role in maintaining the apical–basal polarity and integrity of embryonic epithelia. The family comprises different isoforms in different animals and possesses diverse structural, localization, and functional characteristics. Mutations in the human CRB1 or CRB2 gene may lead to a broad spectrum of retinal dystrophies. Various CRB-associated experimental models have recently provided mechanistic insights into human CRB-associated retinopathies. The knowledge obtained from these models corroborates the importance of CRB in retinal development and maintenance. Therefore, complete elucidation of these models can provide excellent therapeutic prospects for human CRB-associated retinopathies. In this review, we summarize the current animal models and human-derived models of different CRB family members and describe the main characteristics of their retinal phenotypes.

Objective To construct a model of acute ethylene glycol poisoning in SD rats by gavage and compare the brain, heart and kidney injury, so as to provide more reference for related animal experiments and early clinical identification and intervention.Methods Thirty SPF male SD rats were divided into 3 groups by random number table method, 10 rats in blank control group (NC group): gavage normal saline at 12 mL·kg-1; 10 rats in low dose ethylene glycol gavage group (EG-L group) and 10 rats in high dose ethylene glycol gavage group (EG-H group) were gavage 60% and 80% ethylene glycol solution at 12 mL·kg-1. The survival and death of rats in each group were observed within 48 h; and 48 h after modeling, blood sampling from abdominal aorta was performed, and rats were sacrificed to collect brain, heart, kidney and other related organs. The pathological changes of brain, heart and kidney tissues were observed by HE staining, and the calcium oxalate crystals in brain and kidney tissues were observed by Pizzolatto staining. The behavioral changes were determined by the balance ability score. The heart rate and urine volume changes were observed by wearable electrocardiograph sensor and urine volume monitoring. The levels of S100 calcium-binding protein β (S100-β), troponin I (cTnI) and kidney injury molecule-1 (KIM-1) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The levels of oxalate in blood of rats in each group were detected by visible light spectrophotometry.Results The 48 h cumulative survival rates of NC group, EG-L group and EG-H group were 100%, 90% and 70%, respectively. Compared with NC group, the pathological changes of brain and kidney tissues in EG gavage groups were obvious, and obvious calcium oxalate crystal deposition in brain vessels and renal tubules of rats were observed (all P﹤0.05), and the deposition in brain vessels and renal tubules of rats in EG-H group was more obvious (P﹤0.05). The balance ability of the two groups of rats after gavage of EG was lower than that of the NC group (P﹤0.05), and the decrease was more obvious in the EG-H group (P﹤0.05). Compared with the NC group, the heart rate of the rats in the EG-L and EG-H groups was increased at 12 h, 18 h, 24 h, 30 h after gavage (all P﹤0.05), and the urine volume was decreased at 30~36 h, 36~42 h, 42~48 h (all P﹤0.05), and the urine volume of the EG-H group was more obvious at 36~42 h, 42~48 h (P﹤0.05). Compared with the NC group, the serum levels of S100-β and KIM-1 in the EG-L and EG-H groups were increased (all P﹤0.05), and the serum levels of S100-β and KIM-1 in the EG-H group were higher than those in the EG-L group (all P﹤0.05). The oxalate content in the two groups of rats after gavage of EG was increased compared with the NC group (all P﹤0.05), and the oxalate content in the EG-H group was higher (P﹤0.05).Conclusion The rat model of acute ethylene glycol poisoning can be better constructed by gavage of 80% ethylene glycol solution at a dose of 12mL·kg-1. Acute ethylene glycol poisoning can cause multiple organ damage in rats, and the manifestations of poisoning occur and develop in a time-phrased manner.

Abstract Background There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice. Objectives This study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand. Methods Fifty BABL/C mice, 8–10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed. Results Horner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708–726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5–491], median [IQR], bpm) (P 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found. Conclusions This method allows for the successful implementation of SGB in a mouse model.

Abstract Vesicovaginal fistula lacks a standard, established animal model, making surgical innovations for this condition challenging. Herein, we aimed to non-surgically establish vesicovaginal fistula using the magnetic compression technique, and the feasibility of this method was explored using eight female Beagle dogs as model animals. In these dogs, cylindrical daughter and parent magnets were implanted into the bladder and vagina, respectively, after anesthesia, and the positions of these magnets were adjusted under X-ray supervision to make them attract each other, thus forming the structure of daughter magnet-bladder wall-vaginal wall-parent magnet. Operation time and collateral damage were recorded. The experimental animals were euthanized 2 weeks postoperatively, and the vesicovaginal fistula gross specimens were obtained. The size of the fistula was measured. Vesicovaginal fistula was observed by naked eye and under a light microscope. Magnet placement was successful in all dogs, and remained in the established position for the reminder of the experiment. The average operation time was 14.38 min ± 1.66 min (range, 12–17 min). The dogs were generally in good condition postoperatively and were voiding normally, with no complications like bleeding and urine retention. The magnets were removed from the vagina after euthanasia. The vesicovaginal fistula was successfully established according to gross observation, and the fistula diameters were 4.50–6.24 mm. Histological observation revealed that the bladder mucosa and vaginal mucosa were in close contact on the internal surface of the fistula. Taken together, magnetic compression technique is a simple and feasible method to establish an animal model of vesicovaginal fistula using Beagle dogs. This model can help clinicians study new surgical techniques and practice innovative approaches for treating vesicovaginal fistula.

Abstract Acute thrombosis secondary to atherosclerotic plaque rupture is the main cause of acute cardiac and cerebral ischemia. An animal model of unstable atherosclerotic plaques is highly important for investigating the mechanism of plaque rupture and thrombosis. However, current animal models involve complex operations, are costly, and have plaque morphologies that are different from those of humans. We aimed to establish a simple animal model of vulnerable plaques similar to those of humans. Rabbits were randomly divided into three groups. Group A was given a normal formula diet for 13 weeks. Group C underwent surgery on the intima of the right carotid artery with – 80 °C cryofluid-induced injury after 1 week of a high-fat diet and further feeding a 12-week high-fat diet. Group B underwent the same procedure as Group C but without the – 80 °C cryofluid. Serum lipid levels were detected via ELISA. The plaque morphology, stability and degree of stenosis were evaluated through hematoxylin–eosin (HE) staining, Masson trichrome staining, Elastica van Gieson staining (EVG), and oil red O staining. Macrophages and inflammatory factors in the plaques were assessed via immunohistochemical analysis. The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels in groups B and C were significantly greater than those in group A. No plaque formation was observed in group A. The plaques in group B were very small. In group C, obvious plaques were observed in the blood vessels, and the plaques exhibited a thin fibrous cap, a large lipid core, and partially visible neovascularization, which is consistent with the characteristics of vulnerable plaques. In the plaques of group C, a large number of macrophages were present, and matrix metalloproteinase 9 (MMP-9) and lectin-like oxidized LDL receptor 1 (LOX-1) were abundantly expressed. We successfully established a rabbit model of vulnerable carotid plaque similar to that of humans through the combination of cryofluid-induced endothelial injury and a high-fat diet, which is feasible and cost effective.

Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.

The 2023 China Health Report on Spine Degeneration noted a significant increase in lumbar surgery among patients under 35 years old in recent years, indicating a trend towards younger onset of cervical and lumbar diseases. Lumbar intervertebral disc herniation has become a major concern, making the study of disc degeneration pathogenesis and treatment methods clinically significant. At present, human intervertebral disc diseases are primarily diagnosed through imaging due to the challenges of obtaining tissue samples from the spine. Therefore, experimental animals have emerged as alternative research subjects because they are cost-effective, have short experimental cycles, and are easily accessible. Given the structural and physiological differences between human and other animal intervertebral discs, comparing their anatomy and histological characteristics forms the foundation of research into human disc degeneration. The purpose of this paper is to collect and review relevant studies on anatomical and histological structures of intervertebral discs in different animals and conduct a comparative analysis from four aspects, namely, intervertebral disc height, lumbar disc geometry, lumbar disc cartilaginous endplate characteristics, and extracellular matrix components. The results show that humans, kangaroos, sheep, pigs, and rats exhibit similar relative heights between the sixth and seventh cervical vertebrae. Mice possess lumbar disc geometries most akin to humans. Compared to other animals, humans have the thickest cartilaginous endplates and the lowest cell densities. The collagen within the fibrous annulus differs most notably in pigs compared to humans, while water content in the nucleus pulposus is consistent across pigs, sheep, rabbits, rats, and humans. Additionally, this paper describes the commonalities and discrepancies in disc degeneration manifestations between humans and animals, and summarizes modeling methods for disc degeneration in different experimental animals. Ultimately, the aims of this paper is to provide fundamental data for selecting suitable experimental animal models for the study of intervertebral disc degeneration.

Obstructive sleep apnea (OSA) is a common sleep disorder, and its pathophysiological mechanism complex and not fully understood. This article elaborately explores three categories of OSA animal models: natural, direct and indirect, emphasizing their advantages and disadvantages in simulating OSA pathophysiological processes. Natural OSA models primarily focus on spontaneous upper airway obstructions. Direct OSA models induce OSA through direct obstruction of the airway, while indirect OSA models mainly investigate the impacts of chronic intermittent hypoxia (IH) and sleep deprivation (SD) on the organism. Although these models have played a pivotal role in studying the pathophysiological mechanisms of OSA and developing new therapeutic methods, they also present certain limitations and challenges. Future research directions include the development of non-invasive monitoring technologies, establishing OSA-combined models, and the application of gene-editing technologies, aiming to more comprehensively and accurately simulate the complexity and diversity of human OSA, providing more insights into its mechanisms and developing new therapeutic methods.

Abstract In this report, we described a new technique of gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices in a porcine model. As a result, the gynecological procedures were successfully completed. The total operative time was 110 min, while the docking time was 10 min. The estimated blood loss was estimated to be 10 mL with no intraoperative complications. It revealed that gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices appeared to be feasible and safe in the porcine model and has the potential for clinical use in human beings.

Since the identification of the poliovirus in 1908, over a hundred serotypes of enteroviruses have been discovered, capable of causing a range of diseases including hand, foot, and mouth disease, newborn sepsislike syndrome, aseptic meningitis, acute flaccid paralysis, respiratory disorders, and acute hemorrhagic conjunctivitis. In recent years, enteroviruses such as EV-A71 and EV-D68 have exhibited globalized periodic outbreaks, emerging as a significant and indisputable challenge in the field of public health. However, the current preventive and control measures for enteroviruses remain notably limited, necessitating a pressing need to delve deeper into the molecular mechanisms responsible for enteroviral pathogenesis. This will facilitate the development of novel targets and methodologies for the creation of effective, safe, and broad-spectrum antiviral drugs. This comprehensive review focuses on the classification, epidemiology, structure, life cycle, interplay between viral proteins and host factors, pathogenic mechanisms, clinical treatments, and the establishment and application of animal infection models relevant to enteric viruses. The aim is to serve as a theoretical referential basis for the prevention and control of enteroviruses, offering novel perspectives for the development of drugs and the establishment of a vaccine repository dedicated to combating enteroviruses.

Micturition serves an essential physiological function that allows the body to eliminate metabolic wastes and maintain water-electrolyte balance. The urine spot assay (VSA), as a simple and economical assay, has been widely used in the study of micturition behavior in rodents. However, the traditional VSA method relies on manual judgment, introduces subjective errors, faces difficulty in obtaining appearance time of each urine spot, and struggles with quantitative analysis of overlapping spots. To address these challenges, we developed a deep learning-based approach for the automatic identification and segmentation of urine spots. Our system employs a target detection network to efficiently detect each urine spot and utilizes an instance segmentation network to achieve precise segmentation of overlapping urine spots. Compared with the traditional VSA method, our system achieves automated detection of urine spot area of micturition in rodents, greatly reducing subjective errors. It accurately determines the urination time of each spot and effectively quantifies the overlapping spots. This study enables high-throughput and precise urine spot detection, providing important technical support for the analysis of urination behavior and the study of the neural mechanism underlying urination.

Abstract Background Growing evidence showed that acupuncture may improve cognitive function by reducing oxidative stress, key to the pathogenesis in vascular dementia (VaD), but this is yet to be systematically analysed. This study aimed to summarize and evaluate the effect of acupuncture on oxidative stress in animal models of VaD. Method Eight databases including PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, CBM, and VIP were searched since their establishment until April 2023, for studies that reported the effect of acupuncture on oxidative stress in VaD animal models. Relevant literature was screened, and information was extracted by two reviewers. The primary outcomes were the levels of oxidative stress indicators. The methodological quality was assessed via the SYRCLE Risk of Bias Tool. Statistical analyses were performed using the RevMan and Stata software. Results In total, 22 studies with 747 animals were included. The methodology of most studies had flaws or uncertainties. The meta-analysis indicated that, overall, acupuncture significantly reduced the expression of pro-oxidants including reactive oxygen species (standardized mean differences [SMDs] = -4.29, 95% confidence interval [CI]: -6.26, -2.31), malondialdehyde (SMD = -2.27, 95% CI: -3.07, -1.47), nitric oxide (SMD = -0.85, 95% CI: -1.50, -0.20), and nitric oxide synthase (SMD = -1.01, 95% CI: -1.69, -0.34) and enhanced the levels of anti-oxidants including super oxide dismutase (SMD = 2.80, 95% CI: 1.98, 3.61), glutathione peroxidase (SMD = 1.32, 95% CI: -0.11, 2.76), and catalase (SMD = 1.31, 95% CI: 0.05, 2.58) in VaD animal models. In subgroup analyses, acupuncture showed significant effects on most variables. Only partial modelling methods and treatment duration could interpret the heterogeneity of some outcomes. Conclusion Acupuncture may inhibit oxidative stress to improve cognitive deficits in animal models of VaD. Nevertheless, the methodological quality is unsatisfactory. More high-quality research with a rigorous design and further experimental researches and clinical trials are needed to confirm these findings. Systematic review registration This study was registered in PROSPERO (CRD42023411720).

Objective To comprehensively analyze the reported preparation methods for animal models of perimenopausal syndrome (PS), to compare the advantages and disadvantages of various preparation elements and detection indexes, so as to provide useful references for the optimization of the relevant animal models as well as the standardization of their application in the efficacy evaluation of new drugs. Methods In this paper, literature research methods were applied using "perimenopausal syndrome" as the subject term. The publication period of the literature was limited to January 2016 to February 2023. Relevant literature on the preparation of PS animal models was retrieved from databases such as China National Knowledge Infrastructure, Wanfang database, and PubMed. After screening the experimental literature that met the inclusion and exclusion criteria, detailed information on experimental animal strains, modeling methods, duration of drug administration, positive drugs, detection indexes and other relevant information were collected. After the above information was standardized, the PS animal model database was established using Excel 2010 software. The model preparation elements and evaluation indexes were summarized systematically, and the statistical results were processed and analyzed using Excel 2010 software. Results A total of 247 articles were screened. SD rats (164 times, 65.86%) and Wistar rats (35 times, 14.06%) were often used to prepare PS animal models. Bilateral ovariectomy (139 times, 53.87%) and natural aging (43 times, 16.80%) were chosen as modeling methods. The ages of rats used for modeling ranged from 7 weeks to 18 months, with 3-month-old rats (22 times, 21.78%) being the most common. The detection indexes were comprehensively evaluated from multiple perspectives, including serum biochemistry, vaginal exfoliated cell smear, histomorphology, general observation, behavioral observation, and organ tissue protein immunoblotting. Western medical evaluation indexes were commonly used to test the successful preparation of models, with vaginal exfoliated cell smears being the most frequently used method (125 times, 85.04%). A model was considered successfully prepared when estrous cycle disorder or irregularity was observed. Some literature also determined modeling success by detecting a significant decrease in serum estradiol levels (5 times, 3.04%). Traditional Chinese medicine (TCM) syndrome evaluation often used a combination of Chinese and Western medical evaluation indexes for comprehensive evaluation, with researchers determining the TCM syndrome through vaginal exfoliated cell smears supplemented by general observation (3 times, 2.04%). Conclusion There are many methods for preparing PS animal models, but there are still significant differences in the selection of animal species, age, criteria for successful modeling, and TCM syndrome evaluation in the related literature.

Pregnancy and the oestrus cycle are challenging for female patients suffering from von Willebrand disease (VWD). Therefore, our study aimed to investigate the changes in von Willebrand factor (VWF) and factor VIII (FVIII) during pregnancy and the oestrus cycle in our porcine model of von Willebrand disease compared with the wild-type. Plasma analyses regarding primary hemostasis, secondary hemostasis, and VWF multimers, as well as immunohistochemistry analyses of VWF in the uterus and ovary, were performed. For levels of VWF and FVIII activities, significant elevations were seen in the last trimester. Primary hemostasis improved towards the end of pregnancy. In the oestrus cycle, significantly lower VWF values can be seen in the immunohistochemistry of the ovaries during the oestrus, while values were highest in the metoestrus. VWF multimer patterns in pigs were similar to the ones in human VWD patients. In summary, the course of VWF and FVIII during pregnancy and the oestrus cycle in porcine VWD were investigated for the first time. The porcine model seems to be suitable for haemostaseological studies on VWD. This provides an advantage for investigating reproduction-related bleeding and understanding the underlying mechanisms of post-partum hemorrhage or miscarriage in women with VWD.