Abstract: Objective　To observe the characteristics of C57BL/6N-Tg (1. 28HBV) / Vst transgenic hepatitis B virus (HBV-Tg) model mice and analyze their transcriptomic characteristics. Methods　Twenty male HBV-Tg mice were divided into an experimental group and a wild-type ( control) group ( n= 10 mice per group). The virological characteristics of the model mice were evaluated according to serum levels of HBV DNA, HBsAg, and HBeAg, and expression levels of HBsAg and HBcAg in liver tissue. Serum levels of alanine transaminase ( ALT) and aspartate transaminase (AST), hematoxylin and eosin (HE) and Sirius red staining, and hydroxyproline(Hyp) in liver tissue were detected to evaluate the degree of liver inflammation and fibrosis. Liver tissue samples were randomly selected from three mice in each group for RNA extraction for high-throughput transcriptome sequencing. Significantly differentially expressed genes were identified using R software. Functional enrichment of differential genes was determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and genes with significant differences were verified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Results　ALT and AST levels were increased in the model group compared with the normal group, with the result for ALT being more significant (P< 0. 05). HE staining of liver tissue showed enlargement of the liver nucleus and swelling of some hepatocytes in the model group, while Sirius red staining showed a small amount of collagen deposition in the sink area and interlobule in the HBV transgenic group, in the shape of thin lines. A total of 1352 differential genes were obtained by screening ( | logFC | > 2 and P.adj < 0. 05), including 703 up-regulated and 649 down-regulated genes. KEGG analysis suggested that differential genes were mainly enriched in the peroxisome proliferator-activated receptor ( PPAR) signaling pathway, retinol metabolism, fatty acid degradation, and other pathways (P.adj < 0. 05). The main significantly up-regulated genes included Cyp4a10, Cyp4a14, Acot1, Acot3, and Ehhadh, and the significantly down-regulated genes included Scn5a、Apol10b、Igddc4、Cxcl1、9530077C05Rik. The trend was consistent after RT-qPCR detection (P< 0. 05). Conclusions　HBV-Tg mice have a tendency to develop spontaneous fibrosis. Transcriptomic analysis showed that chronic hepatitis B mainly involves PPAR signaling, retinol metabolism, fatty acid degradation, drug metabolism, and other pathways.

Abstract: Objective 　The incidence of coronary microvascular disease ( CMVD) is increasing annually. According to traditional Chinese medicine (TCM), CMVD belongs to the category of “collaterals”, and qi deficiency and blood stasis are the main syndrome type of CMVD. Notably however, no studies have reported on the use of animal models of CMVD with qi deficiency and blood stasis. The current study therefore aimed to establish and evaluate a rat model of CMVD with qi deficiency and blood stasis syndrome. Methods　Forty-five male SD rats were divided randomly into sham group, CMVD group, and CMVD + QXXY group (n= 15 rats per group). Rats in the CMVD + QXXY group were randomly deprived of sleep for 14 ~ 16 h/ day for 6 weeks, and the model of qi deficiency syndrome was established. Animals in the sham group and the CMVD group were fed normally for 6 weeks. After 6 weeks, rats in the CMVD and CMVD + QXXY groups were anesthetized, their chests were opened, and embolic microspheres (40 ~ 120 μm) were injected into the left ventricle. Rats in the sham group underwent thoracotomy without injection of embolic microspheres. On day 7 after operation, relevant detection indicators were measured in each group. Results　Compared with the sham group, the CMVD group showed a significant decrease in left ventricular ejection fraction and left ventricular shortening rate, while the activities of creatine kinase MB isoenzyme ( CK-MB) and lactate dehydrogenase ( LDH) were significantly increased. Heart function, hemorheology, myocardial enzyme index, and the degree of myocardial cell damage differed significantly between the CMVD + QXXY group compared with the sham group. Conclusions　A rat model of CMVD + qi deficiency + blood stasis syndrome can be successfully established by sleep deprivation combined with intraventricular injection of embolic microspheres. This model will be suitable for the study of the pathogenesis of CMVD and the mechanisms of TCM.

Abstract: ObjectiveTo establish and evaluate chemotherapeutic phlebitis model rats induced by vinorelbine via the dorsalis pedis vein. Methods　Rats were divided randomly into control and 4 different concentration of vinorelbine-induced model groups. Control rats were injected with 0. 1 mL normal saline via the dorsalis pedis vein of the hind limb, while other rats were injected with different concentrations of vinorelbine (2, 3, 4, 5 mg/ mL), as above. General observations were performed and the hind limb volume was measured daily for 7 consecutive days to calculate the swelling rate. The rats were then killed and histological changes in the dorsalis pedis vein were observed by hematoxylin and eosin staining. Microstructural changes on the surface of the vascular endometrium were observed by scanning electron microscopy. Results　Injection of 2, 3, 4, 5 mg/ mL vinorelbine via the dorsalis pedis vein significantly induced hind limb swelling in a concentration-dependent manner, peaking on day 3 in each group. The phlebitis rates on day 7 were 50% in the 2 mg/ mL group and 83. 3% in the 3 mg/ mL group. Phlebitis was also induced in the 4 mg/ mL and 5 mg/ mL groups, including grade Ⅲ in 66. 6% and grade Ⅳ in 83. 3%. Histopathology showed inflammatory cell infiltration, wall thickening, lumen stenosis, and thrombosis in the tissues surrounding the veins. Scanning electron microscopy showed destruction of tight junctions of venous endothelial cells, and a rough surface of the vascular lining, resultsing in blood cell adhesion. Conclusions　Injection of 0. 1 mL of 3 ~ 5 mg/ mL vinorelbine via the dorsalis pedis vein could induce red, swollen, and cord-like veins, as well as infiltration of inflammatory cells around the vein, thickened vein walls, lumen stenosis, and thrombosis. In addition, the surface of the venous intima was rough and adhered to numerous blood cells. All these features are consistent with those of clinical chemotherapeutic phlebitis in terms of the symptoms and pathological structure.

Abstract: Objective　To explore the animal model of syndrome used in the study of hot flash phenomenon in women. Methods　Twenty-four female SD rats were divided randomly into three groups: Con group, Ovx group, and tamoxifen group (n= 8 rats per group). Hot flashes were induced by bilateral oophorectomy and intragastric tamoxifen 10 mg/ (kg·d), respectively. Open-field activity, anal temperature, and body surface infrared thermograms were detected on model days 14 and 28. The rats were then killed on day 29 and their uteruses were removed, weighed, and sectioned. Blood estradiol and catecholamine levels were determined by enzyme-linked immunosorbent assay. Gene expression levels of adrenal sex hormone synthetases (Star, Cyp11a1, Cyp17a1, Cyp19a1, Por, Hsd3b2, Hsd17b1) and catecholamine synthetases (Th, Ddc, Dbh, Pnmt) in the adrenal medulla were detected by reverse transcription-polymerase chain reaction. Results　Rat body weight was significantly higher in the Ovx group compared with Con group (P< 0. 01), while body weight increased slowly in the tamoxifen group. The maximum body surface temperature was significantly decreased on day 28 in the Ovx group (P< 0. 01), the difference between the maximum and minimum abdominal temperatures was significantly increased on day 14 (P< 0. 05), the difference between the maximum and minimum temperatures on the back was significantly increased on day 28 (P< 0. 01), and the open-field activity was decreased (P< 0. 01). Compared with the sham operation group, the maximum body surface temperature in the tamoxifen group was significantly decreased (P< 0. 01) but the open-field activity was increased (P< 0. 01). The uterine index was significantly decreased in both models (P< 0. 01). Estradiol levels were significantly decreased (P< 0. 01) and NE and epinephrine were also significantly decreased in the Ovx group compared with Con group (P< 0. 05), and β-EP was also significantly decreased in Ovx group (P< 0. 05). Adrenal Cyp11a1 gene expression was significantly increased (P< 0. 05) while Cyp17a1 and Hsd17b1 gene expression levels were significantly decreased (P< 0. 05) in bilateral ovariectomized rats compared with Con group. Compared with Con group,gene expression levels of Star and Por were significantly increased (P< 0. 01) while Cyp17a1 gene expression was significantly decreased (P< 0. 01) in the tamoxifen group, and Pnmt gene expression was significantly down-regulated in Ovx group (P< 0. 01). Conclusions Bilateral ovariectomized rats can be used for the study of perimenopausal hot flashes, which resemble kidney Yang and Yin deficiency in traditional Chinese medicine.

Abstract: Objective To prepare rat models of liver stagnation syndrome constipation-type irritable bowel syndrome (IBS-C) using single and multi-factor modeling method with different indicators, to provide ideal experimental animal models of IBS-C. Methods　Forty-two SD rats were divided randomly into blank (Normal), cold-water gavage (Cold), restraint (Restrain), tail-clamping (Tail), cold-water gavage + restraint (C + R), and cold-water gavage + tailclamping groups (C + T). Body weight, food intake, water intake, and survival status, as well as open-field behavior, fecal Bristol score, visceral sensitivity, and small intestine propulsion were observed in each group during the modeling period. Pathological changes in the rat colon were observed by hematoxylin and eosin staining, and the serum and colon contents of 5-hydroxytryptamine (5-HT) and vasoactive intestinal peptide ( VIP) were determined by enzyme-linked immunosorbent assay. Results　The body weight in each group decreased after modeling (P< 0. 05, P< 0. 01), the food and water intakes decreased, and serum 5-HT levels increased. The number of fecal particles and Bristol score decreased while the colon 5-HT content increased in the Cold group (P< 0. 05, P< 0. 01); the total distance and average speed of the restraint group in the open field decreased (P< 0. 01); the preference for sugar water in the Tail group decreased (P<0. 01); the preference for sugar water, total open-field distance, small intestine propulsion rate, defecation particles, and Bristol score all decreased, while the colon 5-HT content increased and the VIP content decreased in the C + T group (P<0. 05, P< 0. 01); and the total distance, average speed, and VIP content in the colon decreased in the C + R group (P<0. 05). Except for the Tail group, all the model groups showed visceral hypersensitivity (P< 0. 05, P< 0. 01) compared to the blank group at various pressure values on days 7 and 14 of modeling. Pathological observations showed no significant inflammatory cell infiltration or pathological changes in any of the model groups. Conclusions　The combination of icewater gastric lavage and tail clamping can be used to establish a rat model of liver depression syndrome in IBS-C. This may be the best of the five tested method, and the resulting model may lay the foundation for further systematic and in-depth research into the mechanism of traditional Chinese medicine in preventing and treating IBS-C.

Abstract: ObjectiveTo investigate the effects of oral probiotics on gut microbiota diversity, colony structure, and intergroup differences in mice with subcutaneous colon cancer tumors, based on 16S rRNA sequencing technology. Methods　Twenty-four 6-week-old male BALB/ c mice were divided randomly into normal control group (NC group, n= 8), model group (M group, n= 8), and probiotic + model group (PM group, n= 8) after adaptive feeding for 1 week. Mice in the PM group were given 200 μL probiotic mixed solution (Bifidobacterium longum and Lactobacillus delbrueckii subsp. bulgaricus mixed lyophilized powder, 2 × 10⁸ colony-forming units) by gavage three times/ week for 7 weeks, while the M group and PM group received 200 μL normal saline. At 10 weeks old, 0. 2 mL CT26.WT cell suspension (1 × 10⁷ / mL) was inoculated subcutaneously into the left hind limbs of M group and PM group, while NC group were inoculated with 0. 2 mL normal saline. The general state of mice was observed, the growth of subcutaneous tumor was monitored, and the changes of intestinal flora structure were detected by 16S rRNA sequencing. Results　The subcutaneous tumors of the M group were prominent, and the subcutaneous tumor volume and weight of the PM group were significantly reduced (P<0. 05). Compared with NC group, Alpha diversity index was lower in the M group, and a significant difference of Beta diversity inter groups (P< 0. 01). And supplementation of probiotics had a certain effect on gut microbiota diversity in the M group. Compared with M group, the relative abundance of Bacteroidetes, Proteobacteria, Muribaculaceae,Bacteroides were higher in the PM group, while the relative abundance of Firmicutes, Desulfobacterota, Lachnospiraceae_NK4A136_ group, Alistipes were lower in the PM group. LEfSe analysis showed that Muribaculaceae and Bacteroides in the PM group were different species with high abundance (LDA values > 4). Conclusions 　Oral probiotics may improve the gut microbiota by increasing the relative abundance of beneficial Muribaculaceae and Bacteroides in subcutaneous tumors in mice with colon cancer.

Abstract: Objective　To establish a quantitative polymerase chain reaction (PCR) method for the analysis of human-derived SRY DNA in mouse tissues, and to study the tissue distribution of human umbilical cord mesenchymal stem cells (HUCMSCs) in immunodeficient NOG mice after a single intravenous injection. Methods 　We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues, and validated the standard curve, linear range, accuracy, precision, and stability. Thirty-six NOG mice (18 male, 18 female) were administered 3. 5 × 10⁷ HUCMSCs/ kg by single intravenous injection. Six mice were then anesthetized and dissected after blood collection (EDTA anticoagulation) at 6, 12, 24, and 72 h, and at 1 and 2 weeks, respectively. DNA was extracted from lung, kidney, heart, liver, brain, spinal cord, stomach, small intestine, fat, skin, spleen, testis, uterus, and ovary tissues, and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the humanderived SRY gene in mouse tissues. In addition, 18 NOG mice (9 male, 9 female) were divided into control (n= 6) and treatment groups (n= 12) injected intravenously with 0. 9% sodium chloride and 3. 5 × 10⁷ cells/ kg, respectively. Acute toxic reactions were observed during the administration period, and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs. Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues. Results　The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index. After a single intravenous injection in NOG mice, HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration, with higher concentrations in lung tissues than in blood. The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6 ~ 24 h and 6 ~ 72 h, respectively, and then decreased over time. The distribution of HUCMSCs in other tissues was not measured at all sampling points. The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection, but not at 2 and 4 weeks. No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs. Conclusions　The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible. HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection, and mainly colonized lung tissue at 72 h. A single intravenous administration of HUCMSCs has a good safety profile.

Abstract: Objective　To elucidate the role of the glutathione (GSH) / glutathione peroxidase 4 (GPx4)-mediated ferroptosis pathway in preventing age-related hepatocyte peroxidation injury following aerobic exercise in mice, and to provide a new target for improving liver aging and metabolism disorders. Methods　Twenty specific-pathogen-free C57BL/6 male mice aged 52 weeks were divided randomly into an elderly control group (EC group) and elderly exercise group (EE group) (n= 10 per group). The mice performed moderate-intensity exercise with incremental loads (1 ~ 2 weeks 14 m/ min, 3 ~ 4 weeks 15 m/ min, 5 ~ 10 weeks 16 m/ min, 11 ~ 16 weeks 17 m/ min, 60 min/ day, slope 0°) for 16 weeks. After perfusion of the ascending aorta, the lateral liver lobes were harvested and sectioned for hematoxylin and eosin staining and ultrathin sections were used for transmission electron microscopy. Levels of 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) in the liver and serum interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay. Hepatic glycogen, triglycerides (TG), malondialdehyde (MDA), nicotinamide adenine dinucleotide phosphate (NADPH), and GSH were determined by colorimetry. Hepatic GPx4, glucose transporter (GLUT2), NAD(P)H: quinone oxidoreductase 1 (NQO1), and solute carrier protein 7 family member 11 (SLC7A11) were detected by Western Blot. Results　(1)Oxidative damage to hepatocytes was effectively delayed, normal mitochondrial structure and glycogen storage in hepatocytes were maintained. (2) Hepatic GSH and NADPH contents were significantly increased in EE mice compared with EC mice (P< 0. 01). (3)In addition, liver levels of 8-OHdG, 4-HNE, MDA, and non-heme iron were significantly decreased in the EE group compared with the EC group (P< 0. 01). (4)Expression levels of GPx4, NQO1, and SLC7A11 in the liver were increased (P< 0. 01) while NOX2 expression was decreased (P< 0. 01) in the EE group compared with the EC group. Conclusions　GSH synthesis was increased in aged mice following aerobic exercise, providing reaction substrates for GPx4 and activating the GSH/ GPx4 pathway. Ferroptosis was inhibited, thus improving hepatocyte peroxidation damage caused by aging, and maintaining the normal structure and physiological function of hepatocytes.

Abstract: ObjectiveUsing different sterilization method to sterilize pig specific formula milk powder, exploring the sterilization method and conditions that minimize the loss of nutritional components in formula milk powder. Methods Pig-specific formula milk powder was divided into high-pressure sterilization and irradiation sterilization groups. Formula milk powder in the high-pressure group was sterilized using different sterilization conditions and that in the irradiation group was sterilized using different ⁶⁰Co γ-radiation doses. The sterility and the nutritional contents of the sterilized formula milk powders were determined according to national standards. Results 　The sterility tests for both groups of formula milk powder were negative. Compared to control group, the crude protein contents were significantly lower in formula in the highpressure group sterilized at 121℃ for 30 min and in the irradiation liquid group sterilized at 50 kGy (P< 0. 01). The water, crude protein, and calcium contents were significantly lower (P< 0. 001) in the irradiation group sterilized at 50 kGy. There was no significant difference in the valine, isoleucine, or leucine content under 50 kGy sterilization conditions in the irradiation sterilized group, but all amino acid contents were decreased in the high-pressure sterilization and irradiation sterilized liquid groups (P< 0. 001). Analysis of trace elements showed an increased iron content (P< 0. 001) in formula sterilized at 121℃ for 30 min in the high-pressure sterilization group, increased iron and potassium contents (P< 0. 001) under 25 kGy sterilization conditions in the irradiation sterilization liquid group, and increased magnesium content (P< 0. 01). The magnesium (P< 0. 05) and sodium contents (P< 0. 01) differed significantly in formula treated under 50 kGy sterilization conditions in the irradiation sterilized powder group. VE and VB₂ contents were increased in formula sterilized at 121℃ for 30 min in the high-pressure sterilization group (P< 0. 001), the VE content was increased (P< 0. 05) and the VB₂ content was decreased (P< 0. 001) in formula sterilized under 50 kGy conditions in the irradiation sterilization liquid group, and the VE and VA contents were decreased in formula sterilized at 25 kGy in the irradiation sterilized powder group (P< 0. 001). Conclusions　Sterilization at 121℃ for 30 min result ed in the least loss of nutritional components in the high-pressure sterilization group, while irradiation sterilization result ed in the least loss of nutrients at a dose of 50 kGy. Comparing the two sterilization method, irradiation of milk powder at 50 kGy result ed in the least loss of nutrient content.

Abstract:Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters and dietary amines. It plays a crucial role in the pathogenesis, progress, and treatment of neuropsychiatric disorders. Recent studies have revealed that elevated expression of MAOA in prostate cancer (PCa) is closely associated with tumor progression and drives the heterogeneity of PCa. In this review, we summarize the role of MAOA in the development of PCa in different disease stages, including oncogenesis, development, invasion, metastasis, and drug resistance. We also discuss the involvement of MAOA in the tumor microenvironment and explore the potential utility of MAOA inhibitors. We further propose therapeutic strategies based on targeting MAOA in preclinical models to promote relevant clinical trials. This review aims to provide new potential therapeutic targets for the treatment of PCa.

Abstract:Aging is a process of degenerative change that occurs as a result of time-related accumulation, associated with age-related diseases. Understanding the causes and mechanisms of aging and finding drugs that can effectively delay aging and prevent and cure age-related diseases currently present a great challenge for humans. Aging animal models thus represent an important tool in aging research, and various aging animal models have been created using different aging mechanisms. These different models having specific advantages and disadvantages, making them suitable for different research purposes. This review considers aging rodent models to provide information for aging research.

Abstract:Depression is a complex mental disease with polygenic inheritance and a high incidence. Our understanding of the clinical manifestations and pathogenesis of depression has recently improved. Continuous progress in gene-editing technologies has increased the construction efficiency and reduced the cost of gene-knockout animals, leading to their increasing use in the fields of basic research and drug development for depression and providing a powerful tool for revealing the pathogenesis of depression. In this review, we summarize recent progress in understanding the roles and mechanisms of candidate genes in depression using knockout model mice.

Abstract:Pulmonary fibrosis (PF) is a progressive, interstitial fibrotic lung disease characterized by persistent scar formation in the lung parenchyma, and a reduced quality of life and poor prognosis for patients. The pathogenesis of PF is unknown and there is a lack of effective therapeutic agents; however, animal models are currently the main tool used to explore the pathogenesis of the disease and to find effective therapeutic agents. PF can be induced by various factors and to different degrees according to known etiologies. Among these, bleomycin-induced models are widely used because of their reproducibility and the similarity between the fibrosis pathology and clinical conditions. The main induction method include intratracheal drip, intratracheal nebulization, tail vein injection, intraperitoneal injection, and transnasal inhalation, and these can be classified into single and multiple doses, according to the frequency of induction. Based on the relevant literature, the current review summarizes the characteristics of the bleomycin-induced PF model using different induction frequencies and method, to provide a basis for the application of this model.

Abstract:The zebrafish xenograft model plays an important role in cancer modelling, especially breast cancer xenografts. This model facilitates the real-time observation of tumor cell growth, metastasis, and interactions with the immune system, thus providing novel insights and experimental foundations for breast cancer treatment. Furthermore, the zebrafish xenograft model offers a valuable tool for high-throughput drug screening. This review provides an overview of the contributions of the zebrafish xenograft model to elucidating the mechanisms underlying breast cancer development, and its use in screening anti-tumor drugs and conducting therapeutic research.

Abstract:Animal models of human diseases include experimental animals and related materials established during biomedical research, which in turn play a vital role in medical research. Pigs and humans are similar in terms of their anatomy, physiology, immunology, and genetics. Pigs are thus suitable model animals for biomedical research and have various advantages compared with other model animals. Recent advances in biotechnology, such as genetic engineering, have contributed to a rapid increase in the use of pig models for human disease research. In addition to serving as xenotransplant organ donors and as tools in drug-design studies, pigs can also be used as model animals to study human developmental processes, congenital diseases, and disease-response mechanisms, thus making important contributions to improving human health. This review considers the current status and future applications of pigs as research models for studies of human cardiovascular diseases, cancer, ophthalmology, craniofacial, musculoskeletal, and skin research, reproductive and fetal development, nutrition, microbiome research, brain and neurodegenerative diseases, diabetes, infectious diseases, and vaccine design, as well as for xenotransplantation.