Abstract: Objective 　Explore euscaphic acid uptake and transport mechanisms in Caco-2 cells. Methods Ultra-high performance liquid chromatography-triple quadrupole-mass spectrometry ( UPLC-TQ-MS) was employed to determine the content of euscaphic acid. The effects of various times and temperatures on its uptake were investigated. On the basis of the result of uptake analyses, the effects of various concentrations, P-gp inhibitors, chelating agents, and pH values on its bidirectional transport were explored. Results　Euscaphic acid uptake was (8. 38±0. 87) μg/ mg for 180 min in Caco-2 cells at 37℃. The apparent permeability coefficient (Papp ) values of euscaphic acid at low, medium, and high concentrations were (61. 41±2. 92) ×10-4, (146. 90±14. 91) ×10-4, and (167. 18±6. 72) ×10-4 cm/ s, respectively, which were positively correlated to the concentrations. P-gp inhibitors and chelating agents had no effect on Papp values. A weakly acidic environment (pH= 6) significantly increased the Papp value, and the efflux rate ranged from 0. 8 to 1. 4. Conclusions　Euscaphic acid has good transmembrane permeability in Caco-2 cells, and the uptake mode is mainly passive diffusion. It is not a substrate of P-gp and no cellular bypass transport exists. This study may provide an experimental basis for in vivo intestinal absorption of medicines containing euscaphic acid.

Abstract: Objective　To investigate the difference in tissue distribution of ligustrazine hydrochloride and Salvia miltiorrhiza (Danshen) in acute myocardial ischemia (AMI) model rats. Methods　A rat model of AMI was induced by subcutaneous injection of isoproterenol hydrochloride solution. The rats were then divided into a ligustrazine group, Danshen group, and ligustrazine-Danshen group. Ligustrazine and Danshensu levels in the heart, liver, spleen, lung, kidney, and brain were detected at different time points by ultra-high performance liquid chromatography/ tandem mass spectrometry. Results　Ligustrazine and Danshensu were widely distributed and peaked rapidly in tissues of AMI rats after intravenous injection. Before and after compatibility, the content of ligustrazine was highest in brain tissue and lowest in liver tissue, while the Danshensu content was highest in kidney tissue and lowest in brain tissue, indicating that ligustrazine could penetrate the blood-brain barrier more easily than Danshensu, and the main sites of accumulation were different. The areas under the curves of ligustrazine and Danshensu in the heart as the target organ were significantly increased (P<0. 001). Conclusions　These result suggest that the combination of ligustrazine and Danshen may enhance the therapeutic effect by increasing the distribution of the main pharmacodynamic components in the heart, thus improving the efficacy.

Abstract: Objective　To explore the alterations in the gut microbiota-short-chain fatty acid metabolism axis in a rat model of diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the effect of sodium butyrate on this axis. Methods　Seventeen Wistar rats were divided randomly into three groups. IBS-D was induced by 4% acetic acid enema combined with restraint stress. Sodium butyrate was injected intraperitoneally during the modeling period. The fecal flora was detected by 16S rRNA technology, and the fecal short-chain fatty acid content was detected by liquid chromatography mass spectrometry. Results　Rat body weight, the relative abundance of intestinal probiotics, and fecal butyric acid and valeric acid contents were decreased in rats in the model group compared with the normal group, while the abdominal withdrawal reflex score, fecal water content, and relative abundance of Blautia spp. were significantly increased. Treatment with sodium butyrate significantly increased rat body weights and fecal butyric acid and valeric acid contents, and decreased the AWR score, fecal water content, and relative abundance of Blautia spp. , compared with the model group. Conclusions　Sodium butyrate can alleviate diarrhea and colon visceral hypersensitivity in IBS-D rats by improving the imbalance in the gut microbiota-short-chain fatty acid metabolic axis.

Abstract: Objective　To evaluate the risk of bias and reporting quality of animal experimental studies on the use of acupuncture for hypertension, and analyze the deficiencies in experimental design, implementation, and reporting, to reduce the risk of bias and improve the reporting quality of animal studies. Methods　We searched the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Periodical, Chinese Biomedical Literature, Web of Science, PubMed, Embase and The Cochrane Library databases from inception to October 8, 2022. Two researchers independently screened experimental studies related to acupuncture interventions in hypertensive animals according to the eligibility criteria. The SYRCLE’s tool and the ARRIVE guidelines 2. 0 were used to evaluate the risk of bias and reporting quality of the included studies. The data were extracted using Excel 2019 and a descriptive analysis was conducted. Results　A total of 79 animal experiments on the use of acupuncture for hypertension were included, including 17 and 21 published in Chinese core/ Chinese Science Citation Database-indexed journals and Science Citation Index journals, respectively. The result of SYRCLE’s tool analysis showed that five of the 10 items were evaluated well, while the rest had an unclear or high risk of bias. Of the 79 included articles, 19 had a low risk of bias, while the remaining studies had some risk of bias. The result of the ARRIVE guidelines 2. 0 indicated that 19 of the 38 sub-items were well reported, while the rest were poorly reported. The reporting quality was good for 51 articles but the remaining studies were inadequately reported. Conclusions　The risk of bias in animal experiments of acupuncture intervention for hypertension is currently high and the reporting quality is generally low. The inadequate description of some important items affected the reproducibility of the experiments and the translation of the result. SYRCLE’s tool and ARRIVE guidelines 2. 0 should be referred to during the experimental design and reporting of studies, thus improving the standardization and reporting quality of animal studies of acupuncture for hypertension.

Abstract: Objective　To investigate the effects of Bushen Jianpi Kaixin formula (BSJPKXF) on the learning and memory abilities of Alzheimer’s disease (AD) model rats, the related autophagy and apoptosis in their cortex, and the underlying mechanism of BSJPKXF. Methods　Sixty rats were randomly divided into six groups (n=10): control group, AD group, Bushen group (BS, 3. 6 g/ (kg·d)), Jianpi group (JP, 4. 05 g/ (kg·d)), Kaixin group (KX, 2. 34 g/ (kg·d)), and Bushen Jianpi Kaixin group (BSJPKXF, 9. 99 g/ (kg·d)). The AD model was established by intraperitoneal injection of D-gal. Rats in BS, JP, KX and BSJPKXF groups were gavaged with corresponding drugs once a day. Rats in control and AD groups were treated with an equal volume of normal saline once per day. After 4 weeks, learning and memory abilities were assessed by the Morris water maze. The open-field test was used to assess cognitive functions. LC3-I, LC3-II and Beclin1 expression in cerebral cortical tissues was detected by Western blot. Bax and Bcl-2 expression in cerebral cortical tissues was detected by immunohistochemistry. Beclin1, P62, Bax and Bcl-2 mRNA expression in cerebral cortical tissues was detected by RT-PCR. Results　Compared with the control group, D-gal significantly decreased the spatial learning and memory abilities in the AD group (P<0. 01), decreased Beclin1, LC3-I/ LC3-II and Bcl-2 expression and the Bcl-2/ Bax ratio, and increased P62 and Bax mRNA expression (P<0. 01). After treatment, compared with the AD model group, Bushen Jianpi Kaixin formula improved the spatial learning memory ability in the BSJPKXF group (P<0. 01), increased Beclin1, LC3-I/ LC3-II and Bcl-2 expression and the Bcl-2/ Bax ratio, and decreased P62 and Bax mRNA expression (P<0. 01). Conclusions　Bushen Jianpi Kaixin formula improved cognitive impairment in AD rats. The mechanism was presumed related to the reduction of neural autophagy and apoptosis.

Abstract: Objective　To study the role of the phosphoinositide 3-kinase (PI3K) / Akt/ mammalian target of rapamycin (mTOR) signaling pathway in the pathogenesis of transfusion-related acute lung injury (TRALI) in rats. Methods 　A rat model of TRALI was established via trauma-blood loss-massive transfusion, and pulmonary histopathological changes were detected by hematoxylin and eosin staining. Protein and mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in peripheral blood or lung tissues were detected by enzymelinked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction, respectively. Expression levels of PI3K/ Akt/ mTOR signaling pathway-related proteins and of the apoptosis-related proteins Bax, Bcl-2, and Caspase3 were detected by Western blot. Results　Alveolar tissue structure was seriously damaged and inflammatory cell infiltration and edema were evident in TRALI model rats. Expression levels of the inflammatory cytokines TNF-α, IL-6, and IL-1β were significantly increased in peripheral blood and lung tissues (P<0. 05). The PI3K/ Akt/ mTOR signaling pathway was activated, the p-mTOR/ mTOR ratio was significantly increased, expression levels of the apoptotic proteins Bax and Caspase3 were inhibited, and expression of the anti-apoptotic protein Bcl-2 was increased (P<0. 05). Conclusions mTOR, as a potential drug target, may represent an important strategy for the clinical prevention and control of TRALI, by defining the exact timings of its protective and damaging effects and selecting the optimal medication time, in light of the complex mechanism of TRALI.

Abstract: Objective　To investigate the effect and molecular mechanism of taxifolin (TAX) on myocardial hypertrophy in spontaneously hypertensive rats (SHRs). Methods　Twenty-four SHRs were divided into an SHR control group (SHR group), TAX group (20 mg/ kg), and TAX+PERK activator CCT020312 (CCT) group (20 mg/ kg TAX+2 mg/ kg CCT) with eight SHRs per group. Eight Wistar-Kyoto (WKY) rats with normal blood pressure were used as the normal control group ( WKY group). All animals were administered corresponding drugs for 8 weeks of continuous treatment. During the experiment, changes in blood pressure were observed. After the treatments, the thickness of the diastolic ventricular septum (IVSd), the thickness of the systolic ventricular septum (IVSs), and the left ventricular ejection fraction (LVEF) were measured by echocardiography to determine the degree of myocardial hypertrophy and cardiac functions. The cardiac index and left ventricular index were calculated. Hematoxylin-eosin (HE), wheat germ agglutinin (WGA), and Masson staining were performed to evaluate pathological changes of myocardial tissue. Real-time quantitative PCR (qRT-PCR) was performed to measure the mRNA expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), type I collagen α1 chain (COL1A1), and type Ⅲ collagen α1 chain (COL3A1) in myocardial tissues. Western blot was performed to detect expression of protein kinase R-like endoplasmic reticulum kinase (PERK)-activator of transcription 4 (ATF4) pathway-related proteins in cardiac muscle. Results　After the treatments, compared with the WKY group, systolic blood pressure (SBP), diastolic blood pressure (DBP), IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, collagen volume fraction (CVF), myocardial tissue ANP, BNP, COL1A1 and COL3A1 mRNA expression, glucose-regulated protein 78 (GRP78), ATF4, and C/ EBP homologous protein (CHOP) protein levels and the p-PERK/ PERK ratio were increased in the SHR group (all P<0. 05), and LVEF was decreased (P<0. 05). Compared with the SHR group, SBP, DBP, IVSd, IVSs, cardiac index, left ventricular index, myocardial cell cross-sectional area, CVF, myocardial tissue ANP, BNP, COL1A1, and COL3A1 mRNA expression, GRP78, ATF4, CHOP protein levels, and the p-PERK/ PERK ratio were decreased in the TAX group (all P<0. 05), and LVEF was increased (P<0. 05). CCT020312 partially reversed the protective effects of TAX on cardiac functions and hypertrophy. Conclusions　TAX improves hypertensive myocardial hypertrophy by inhibiting endoplasmic reticulum stress, and its mechanism may be related to inhibiting the PERK-ATF4 pathway.

Abstract:In view of the problems in ethical review of domestic experimental animals for scientific research and the lack of ethical review of experimental animals for teaching, we investigated the relevant literature at home and abroad as well as the administrative regulations, national standards, industrial standards, local standards, and group standards related to the welfare and ethical review of experimental animals. This article explores the developmental process of ethical review of experimental animal welfare in China in the last 30 years, analyzes and summarizes many problems in the practical work of ethical review and the supervision and management of experimental animal welfare for scientific research, and summarizes the aspects that should be involved in ethical review education of experimental animal welfare in scientific research and teaching activities. The aim is to provide a reference to establish ethical review of experimental animal welfare for teaching in China and the content arrangement of experimental animal welfare courses in medical colleges and provide a reference for efficient ethical review of scientific research projects and articles related to animal experiments.

Abstract:Severe asthma, which requires high doses of glucocorticoids in combination with other medications to maintain symptom control or is uncontrollable even with these treatments, is currently a challenge in the clinical management of asthma. The establishment of a stable and reproducible animal model that closely mimics the pathophysiological and clinical characteristics of patients with severe asthma is important for in-depth study of severe asthma pathogenesis, identifying potential therapeutic targets, and developing targeted drugs. This article reviews studies related to the establishment of animal models of severe asthma in the past 10 years and summarizes the recent progress in the establishment and evaluation of animal models of severe asthma from three aspects: selection of the animal, establishment protocols, and model pathological phenotypes. This review summarizes and analyzes the current progress in the establishment of SA animal models, and provides a reference for severe asthma basic research using animal models.

Abstract:Pulmonary arterial hypertension is a chronic progressive disease that, if not treated promptly, can ultimately lead to right heart failure and even death. To explore the pathogenesis of pulmonary arterial hypertension and develop more effective treatments, it is necessary to establish an experimental model corresponding to its pathogenesis. In this review, PubMed, ScienceDirect, Wiley, and CNKI were used to search the relevant literature. The establishment method and research progress of experimental models of pulmonary arterial hypertension in recent years were systematically summarized. Moreover, the pathological characteristics involved in these experimental models were classified and discussed to provide a reference to study the pathogenesis of pulmonary arterial hypertension.

Abstract:Premenstrual dysphoric disorder (PMDD) is a subtype of premenstrual syndrome with high prevalence in women during their reproductive life. It has physical symptoms such as breast tenderness and headache as well as serious emotional symptoms such as anxiety, depression, and irritability. These symptoms are specific to the menstrual cycle. They appear before menstruation and disappear within a week after its completion. PMDD is a health threat for females. In the Diagnostic and Statistical Manual of Mental Disorder (Fifth edition ed. DSM-5), PMDD is one of the five types of depression. Current studies on the pathological mechanism of PMDD mainly focus on hormone and receptor expression, which is the theoretical basis of animal model establishment. Animal models that recapitulate the clinical symptoms of humans are very important to connect basic research to clinical research, which is also crucial to explore the pathogenesis and develop appropriate drugs. Although many kinds of animal models of PMDD have been used in various studies, many limitations result in a barrier to further investigate PMDD. Therefore, this review collates the pathogenesis research of PMDD and discusses the existing animal models of PMDD to provide a reference for PMDD-related mechanism research and drug development.

Abstract:Cough is a common clinical symptom. The incidence of chronic cough without significant abnormalities on chest radiography has recently increased, and its complex etiology and high rates of misdiagnosis and mismanagement have received attention. Cough hypersensitivity has been identified as an important clinical and pathophysiological feature, associated with transient receptor potential pathway activation, airway inflammation, neural pathways, and cough-center facilitation; however, the mechanisms are complex and further detailed studies are needed. Information on cough mechanisms has important implications for the development of new drugs, improvements in clinical efficacy, and the reduction of socioeconomic burdens. Animal models of cough are crucial for experimental research and elucidating the mechanisms responsible for cough. Animal models of cough are currently divided into simple cough models and disease cough models; however, its complex pathogenesis and multiple causes mean that there is no unified standard for preparing cough models, and these continue to be modified and improved. The current review discusses the mechanisms, methods and research progress of animal cough models, and comprehensively summarizes the research statuses of these models from the perspectives of animal selection, establishment, and the application of simple and disease cough models, by reviewing the recent relevant global literature. We present a comparative evaluation and reflect and elaborate on the current problems in preparing cough models, to provide references for the preparation of animal models for experimental research and for indepth research on the pathogenesis and treatment strategies of cough.

Abstract:Keratitis is a common ophthalmic disease with a high rate of blindness. This article reviews the relevant literature on animal models of keratitis, summarizes and analyzes the mechanisms of existing animal models of keratitis, and evaluates the clinical anastomosis degree of traditional Chinese and Western medicines in combination with the established clinical diagnostic standards of traditional Chinese and Western medicines, analyzes their advantages and disadvantages, and provides suggestions. Most existing models are based on Western medical theories and lack the diagnostic standards of traditional Chinese medicine. The model is mostly established by a single factor that cannot simulate the actual lesion process of the disease. Diagnosis of the model lacks apparent indicators. It is recommended that animals are modeled by combining disease evidence. It is very important to prepare animal models of keratitis with high clinical compatibility and establish efficient evaluation standards to better understand the occurrence and development of keratitis in modern medical experiments and effectively prevent and treat the disease.

Abstract:Ferroptosis has recently been proposed as a novel form of programmed cellular necrosis, which occurs in various diseases, with serious impacts on human health. Numerous studies have shown that inhibition or promotion of ferroptosis can improve aging and aging-related diseases, and have highlighted an important role for traditional Chinese medicine. This paper reviews the effects and mechanisms of ferroptosis on aging and aging-related diseases, as well as recent research progress in the use of traditional Chinese medicine for the treatment of these diseases, with the aim of providing more options for the treatment and prevention of aging and aging-related diseases.

Abstract:Multiple sclerosis ( MS) is a neurodegenerative disease mainly characterized by inflammatory demyelination in the central nervous system in humans, accompanied by axonal damage, gliosis, and inflammatory cell infiltration. Daily feeding with the copper chelator dicyclohexanone oxalyl dihydrazone (cuprizone, CPZ) can induce demyelination, oligodendrocyte apoptosis, proliferation of oligodendrocyte progenitor cells, and activation of astrocytes and microglia in the central nervous system in mice, while gradual remyelination occurs once CPZ is omitted from the meals. A CPZ-induced model is therefore commonly used to study demyelination and remyelination of MS. This paper focus on the construction of the CPZ mouse model, oligodendrocytes, astrocytes, microglia, and myelin regeneration, and discusses the characteristic therapies for MS in the CPZ model, to provide a theoretical basis for the wide application of this model in scientific research and medical practice.

Abstract:Inflammatory bowel disease (IBD) is a global idiopathic disease involving the ileum, rectum, and colon. The early clinical symptoms of IBD include abdominal discomfort, diarrhea, hematochezia, fever, fatigue, and weight loss. The diagnosis of IBD is based on a comprehensive evaluation of relevant clinical manifestations, endoscopic examination result, and histopathological characteristics of tissue specimens. Biological agents, oral corticosteroids, salicylic acid, and surgery are the main conventional treatments for IBD. Considerable progress has recently been made in elucidating the pathogenesis of IBD. In clinical practice, complex interactions among genetic susceptibility, environmental factors, and the intestinal mucosal barrier are thought to lead to abnormal oxidative stress, autophagy, and a mucosal immune response. This paper briefly summarizes and expounds research progress into genetic and environmental factors, intestinal mucosal barrier function, oxidative stress, autophagy dysfunction, and the adaptive immune response, to provide a basis for further research and the development of treatment method and improvements in clinical efficacy.

Abstract:Articular cartilage is devoid of blood vessels, lymphatic vessels, and nerves, making it inherently incapable of self-repair. Consequently, cartilage injuries often fail to heal naturally, necessitating the use of palliative, reparative, and regenerative treatments. Among these approaches, stem cell therapy has a great potential for the treatment of articular cartilage injuries. Notably, bone marrow mesenchymal stem cells (BMSCs), a well-established stem cell type, are extensively employed in cartilage repair therapy because of their unique biological characteristics. The objective of this article was to review the current domestic and international literature on the method of BMSC extraction, phenotype identification, multidirectional differentiation capacity, and their recent application in repairing articular cartilage injuries. The ultimate goal is to provide valuable insights into the precise and efficient treatment of cartilage injuries using BMSCs, thereby serving as a useful reference for medical practitioners in this field.