Abstract: Objective　To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia. Methods　The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate. The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes, pathological changes, non-target metabonomics and network pharmacology. Results　Baicalein could reduce the contents of serum uric acid, creatinine and blood urea nitrogen, reduce the inflammatory injury of renal tissue, up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein. Nine disease-related targets such as BCL2, SIRT1 and XDH were screened by network pharmacology. Six key metabolic pathways including nicotinic acid and nicotinamide metabolism, caffeine metabolism and purine metabolism were screened by metabonomics analysis. Conclusions　Baicalein can treat hyperuricemia and reduce renal injury, and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.

Abstract: Objective　To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells (VSMCs) induced by homocysteine (Hcy). Methods　Human VSMCs were cultured in vitro and divided into a Control group (0 μmol/L Hcy) and a Hcy group (100 μmol/L Hcy). After intervention, expression levels of pro Caspase-1,gasdermin D (GSDMD), N-GSDMD, and NLR family pyrin domain containing 3 (NLRP3) were detected by Western blot. MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction. Interleukin (IL)-1β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay. Cells were also transfected with control miR-22-3p (miR-22-3p-NC), miR-22-3p-mimic, and miR-22-3p-inhibitor, to observe the effects on VSMC pyroptosis induced by Hcy. Results　Expression levels of pro Caspase-1, GSDMD, N-GSDMD, and NLRP3 in VSMCs were increased (P<0.05), IL-1β and IL-18 levels were increased (P<0.01), and the relative expression level of miR-22-3p was reduced (P<0.01) in the Hcy group compared with the Control group. Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1, GSDMD, N-GSDMD, and NLRP3 in VSMCs (P<0.01), and significantly decreased levels of IL-1β and IL-18 (P<0.01), while transfection with miR-22-3p inhibitor significantly increased the expression levels of pro Caspase-1, GSDMD, N-GSDMD, and NLRP3 in VSMCs (P<0.01) and significantly increased the levels of IL-1β and IL-18 (P<0.05). Conclusions　MiR-22-3p may delay Hcy induced VSMC pyroptosis.

Abstract: Objective　To determine the blood physiological and biochemical indexes in the inbred SHANXI MU strain of spontaneous type 2 diabetes (T2DM) Chinese hamsters. Methods　Chinese hamsters with spontaneously developed T2DM and normal hamsters (n=10 hamsters per group), aged 12 months, were selected for the study. Fasting blood samples were collected and 15 physiological parameters and 16 biochemical indicators were analyzed using a Sysmex XT automated hematology analyzer and Hitachi fully automatic biochemical analyzer. Results　The white cell count, red cell count, platelet count, hemoglobin level, alanine transaminase, aspartate transaminase, glutamate, total cholesterol, triglycerides, and uric acid all differed significantly between the diabetic and control groups (P<0.05). Conclusions The change of blood physiological and biochemical indexes in the Chinese hamster spontaneous T2DM model were in line with the trend in human T2DM incidence, thus providing basic data for the application of this model.

Abstract: Objective　To compare strain and gender differences between ICR and C57BL/6J mouse chronic fatigue syndrome models and provide experimental evidence for the selection of model animals for chronic fatigue syndrome. Methods　ICR and C57BL/6J mice (half male and half female) were injected intraperitoneally with polyinosinic polycytidylic acid (Poly I:C) every three days and forced to swim daily. The modeling was performed for 15 consecutive days, during which the weight and food intake of the mice were measured, and fatigue scores were assessed. After the modeling was completed, behavioral tests were carried out, including exhaustive swimming, tail suspension, mechanical pain threshold, and elevated plus maze. Results　Compared with the control group, both strains of model mice had significantly decreased exhaustion times in the exhaustive swimming test(P<0. 05,P<0. 01), significantly increased immobility time in the tail suspension test(P<0.05,P<0.01), and a significantly decreased mechanical pain threshold(P<0.05,P<0.01), and male model mice had significantly decreased open arm entry time and frequency in the elevated plus maze(P<0.05,P<0.01). The weight of model male C57BL/6J mice significantly decreased(P<0.05,P<0.01). The weight of model female ICR mice increased after a significant reduction(P<0.05). The exhaustion time of control C57BL/6J mice was significantly lower than that of control ICR mice(P<0.01). The immobility time of model C57BL/6J mice was significantly greater than that of model ICR mice(P<0.01). Conclusions　There were differences between the two strains of mice in terms of weight change, fatigue level, and depression. Within the same strain, there were differences between males and females, and the anxiety level of males was higher than that of females.

Abstract: Objective　To observe the changes to, and possible mechanism of, intestinal permeability in pigs without direct injury after an abdominal- and intestinal-penetrating injury from firearms in cold environment at high altitudes. Methods　Fifty-five experimental pigs were divided into two groups: high-altitude cold group (HC) and low altitude normal temperature group (LN). According to the observation time, each group was divided into five experimental subgroups: 0 h, 2 h, 4 h, 8 h, and 24 h. There were six pigs in each HC subgroup and five pigs in each LN subgroup. After euthanasia, intestinal tissues were taken, and the levels of the inflammatory factors TNF-α, and IL-6 in intestinal homogenate and the concentrations of intestinal permeability-related proteins DAO and D-lactate acid in blood were detected by ELISA method. The intestinal tissues of experimental pigs were taken at 0 h and 8 h for LN and 8h for HC, and intestinal pathological changes were observed and scored after HE staining. The concentrations of Occludin, ZO-1,Claudin-3, TLR4, NF-κB, and MLCK (proteins related to intestinal permeability) were detected by Western blot to explore the effect of a cold environment at high altitude on secondary intestinal permeability changes after injury and the possible mechanisms. Results　Both the HC group and LN group experienced typical abdominal intestinal penetrating injuries, and there were no significant differences in their abdominal infection scores or intestinal adhesion (P>0.05). The levels of DAO and D-LA in the serum of experimental pigs in the HC and LN groups gradually increased over time. The levels of DAO and D-LA in the HC group were significantly higher than those in the LN group at all time points (P<0.01 or P<0.001). The fastest increase in DAO and D-LA in the HC group was 4 h to 8 h, while in the LN group, it was 8 h to 24 h. The pathological score of intestinal tissue in the HC group was significantly higher than that in the LN group of experimental pigs (P<0.01). The inflammatory factors TNF-α and IL-6 both increased over time in the intestinal tissue of LN and HC groups. The most significant time point for a increase of inflammatory factors in the HC group was 4 h to 8 h, while in the LN group, it was 8 h to 24 h. The intestinal tissue IL-6 and TNF-α levels of experimental pigs in the HC group were higher than those in the LN group the entire time (P<0.05, P<0.01, or P<0.001). The levels of occludin and ZO 1 in the HC group at 8 h decreased significantly compared to those of the LN group at the 8 h time point (P<0.05), while claudin-3 showed a significant decrease in LN (P<0.001). In the HC group, TLR4, NF-κB, and MLCK were both higher than those in the LN group at 8 h, and the difference was statistically significant (P<0.05). Conclusions　A high altitude cold environment can lead to a secondary increase in intestinal permeability after abdominal-penetrating firearm injury, and its mechanism may be related to the TLR4/NF-κB/MLCK pathway.

Abstract: Objective　To investigate the effect of Inonotus obliquus extract on Crohn’s disease and its mechanism by proteomics technology. Methods　Crohn’s disease (CD) model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). A total of 48 SD male rats were randomized into control, model, Inonotus obliquus low-dose (200 mg/kg), medium-dose (400 mg/kg), high-dose (800 mg/kg) groups, and positive control group (mesalazine, 225 mg/kg). The disease activity index (DAI) score and the colonic mucosal injury index (CMDI) score were assessed after one week of drug intervention. HE staining was used to observe the histopathological changes in the colon, and ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in the serum. Proteins were extracted from the colonic tissues of the control group, model group, and Inonotus obliquus high-dose group, and bioinformatics analysis was performed for the proteins identified by quantitative proteomics. Finally, Western blot and RT-qPCR were employed to verify the key proteins. Results 　Compared with the model group, the DAI, CMDI and HE staining scores were significantly decreased in the medium and high dose groups (P<0.05 or P<0.01), as well as the levels of inflammatory factors IL-1β, IL-6 and TNF-α in serum (P<0.05 or P<0.01). Proteomic tests showed that there were 199 differentially expressed proteins (DEPs) between the Inonotus obliquus high-dose group and the model group, of which 63 DEPs were related to CD. Bioinformatics analysis showed that these 63 DEPs were mainly involved in NOD-like receptor signaling pathway, calcium signaling pathway, necroptosis, and other pathways. Consistent with proteomic result, expressions of Vdac1 and Trpv2 were confirmed by Western blot and RT-qPCR in colon tissue. Conclusions　Inonotus obliquus extract may regulate NOD-like receptor signaling pathway, calcium signaling pathway, and necroptosis by interfering with the expression of Vdac1 and Trpv2, so as to achieve the effect of treating CD.

Abstract: Objective　To investigate the therapeutic effect and underlying mechanism of Qishishenshu Capsule on renal fibrosis in mice with early diabetic nephropathy (DN). Methods　A DN mouse model was established by multiple injections of streptozotocin. The mice were randomly divided into a normal group (NC), model group (DN), and Qishi group (QS) (0.9 g/(kg·d)), with eight mice in each group. Mice were gavaged continuously for 4 weeks, and fasting blood glucose (FBG) was measured weekly. Four weeks later, urinary albumin/creatinine (UACR), serum creatinine, and blood urea nitrogen were measured. Hematoxylin-eosin, periodicacid-Schiff, and Sirius red staining were used to analyze renal pathological changes. Real-time fluorescence quantitative reverse-transcription polymerase chain reaction was used to detect the mRNA levels of fibronectin (FN), collagen type I alpha 1 (Col1a1), and α-smooth muscle actin (αSMA). Immunohistochemistry and Western blot were performed to detect FN, collagen type I (Collagen I), collagen type III (Collagen III), α-SMA, Podocin, Nephrin, and transforming growth factor-β1/SMAD family member2/3 (TGF-β1/Smad2/3) pathway-related proteins. Results　Compared with mice in the NC group, those in the DN group showed significantly higher levels of FBG and UACR (P<0.001), and mesangial hyperplasia, basement membrane thickening, and collagen deposition in the renal tissue. The mRNA levels of FN, Col1a1, and α-SMA were increased (P<0.05). Protein levels of Podocin and Nephrin were decreased (P<0.05). The levels of FN, Collagen I, Collagen III, α-SMA, and TGF-β1/Smad2/3 pathway proteins were increased (P<0.05). Compared with the DN group, the QS group’s level of UACR was decreased (P<0.05), their renal pathological injury was alleviated, and mRNA levels of FN, Collagen I, and α-SMA were attenuated (P<0.05); whereas their protein levels of Podocin and Nephrin were elevated (P<0.05). The levels of FN, Collagen I, Collagen III, α-SMA, and TGF-β1/Smad2/3 pathway proteins were also decreased (P<0.05). ConclusionsQishishenshu Capsule improved renal fibrosis in DN mice, probably through the inhibition of the TGF-β1/Smad2/3 signaling pathway.

Abstract: Objective　To investigate the mechanism by which EFHD2 affects the occurrence and progression of breast cancer based on the NOX4/ROS signaling pathway. Methods　Cells were divided into an NC-shRNA group and EFHD2-shRNA group. A lentiviral vector for EFHD2 silencing and a control vector were constructed and used to transfect MDA-MB-23 and MCF-7 breast cancer cells. The transfection efficiency was verified by qRT-PCR. A CCK8 assay was used to detect cell proliferation activity. A plate cloning assay was employed to measure cell colony formation ability. A scratch test was used to detect cell migration, and a Transwell assay used to assess cell invasion. Flow cytometry was applied to detect apoptosis and ROS levels. qRT-PCR was used to analyze the mRNA expression of GLUT1, PDK1, PFK1, PKM2, PDH, and LDH, while Western blot was applied to detect the expression of Cleaved caspase-3, MMP-2, and NOX4 proteins. Results　Compared with the NC-shRNA group, the EFHD2-shRNA group’s EFHD2 expression was significantly decreased and its cell survival and colony formation ability were weakened. The apoptosis rate and the expression of the pro-apoptotic protein Cleaved caspase-3 increased. The cell migration distance was shortened, while the number of invading cells and the expression of MMP-2, which promotes migration and invasion, were decreased. The levels of lactic acid and GLUT1, PDK1, PFK1, PKM2, and LDH decreased, while the levels of ATP and PDH increased. Streaming result showed that ROS levels were reduced and NOX4 protein was down-regulated after silencing EFHD2. Conclusions　EFHD2 inhibits ROS production by regulating the NOX4/ROS signaling pathway, causing lactic acid and glucose accumulation, promoting the apoptosis of breast cancer cells, and inhibiting cell proliferation, migration, and invasion.

Abstract: Objective　To explore the biological effect of transcription factor B1, mitochondrial (TFB1M) on hepatocellular carcinoma (HCC) cells, and to explore the molecular mechanism of its regulation on malignant metastasis of HCC. Methods　 The expression level of TFB1M in liver cancer and its relationship with clinical characteristics of patients with HCC was analyzed based on TCGA-LIHC and GEO databases. Based on the median expression level of TFB1M, the TCGA-LIHC samples were divided into low expression group of TFB1M (n=170) and high expression group of TFB1M (n=170), and GSEA was used for gene set enrichment analysis.The overexpressed TFB1M plasmid was constructed to transfect HepG2 and Huh7 cells. Cell migration and invasion were assessed by scratch healing and Transwell chamber assays. Results　 The expression of TFB1M was significantly decreased in HCC, and the expression of TFB1M was related with gender in HCC. The Results of GSEA analysis indicated that the low expression of TFB1M might be related to liver cancer subclass proliferation up gene set, stem cell hepatocellular carcinoma gene set, and extracellular matrix assembly gene set in HCC. Overexpression of TFB1M remarkably attenuated the migration and invasion activity of HCC cells. Conclusions　The expression of TFB1M was significantly decreased in HCC, and overexpression of TFB1M could attenuated the migration and invasion activity of HCC cells.

Abstract:Laboratory animals have played an important role in human health developments. Advocating the ethics and welfare of laboratory animals is a dual manifestation of technological progress and human civilization, and establishing an ethical review of laboratory animal welfare is an effective guarantee for achieving their welfare. Although the regulation of animal welfare ethics in China has developed rapidly in recent years, there are still many problems that need to be addressed. This article considers the understanding and recognition of the ethical concepts related to the welfare of laboratory animals. It summarizes and discusses some issues discovered during the ethical review of laboratory animal welfare in medical research, and puts forward personal suggestions for exchange and mutual reference.

Abstract:Animal Biosafety Level 3 Laboratory (ABSL-3), as a basic support platform for the national biosafety system for emerging and re-emerging infectious diseases, provides a crucial infrastructure for the study of the biological characteristics of highly pathological pathogenic microorganisms, prevention and treatment means.The ABSL-3 laboratory also provides an important support for the university “industry-academia-research” combination. The normal operation of the ABSL-3 laboratory and the smooth development of scientific research work can not be separated from the careful planning and effective implementation of emergency preparedness work. In addition, the reasonable design and layout of the laboratory is also a key factor to avoid and reduce accidents. This paper combines Yangzhou University ABSL-3 construction and management practices, starting from the preparation of the emergency plan on the laboratory construction and layout, daily operation and sewage treatment, terminal disinfection of specific measures, and emergency disposal and other aspects of attention to be introduced, in order to provide a useful reference for the future operation of various pathogenic microorganisms biosafety laboratories.

Abstract:Diarrhea is a common and frequent disease in clinical practice. Many factors cause diarrhea, and numerous research method with animal models of diarrhea have been explored. Despite this, drugs for the treatment of diarrhea in clinical practice are limited, and some existing drugs are only suitable for diarrhea caused by a single factor. Therefore, the construction and selection of appropriate animal models of diarrhea are not only important for in-depth studies of the pathogenesis, but are also effective means for the clinical screening and evaluation of drugs for comprehensively preventing and treating diarrhea. This article reviews the literature on the establishment and evaluation of animal models of functional, bacterial, viral, and symptomatic diarrhea, as well as progress of therapeutic drug research, to provide a reference for animal experimental research into the prevention and treatment of diarrhea.

Abstract:Pathological mood changes, mainly depression, occurring during the diagnosis and treatment of breast cancer are referred to as breast cancer-related depression (BCRD). Numerous epidemiological and clinical studies have confirmed that BCRD is a complex condition that is difficult to treat and has a poor prognosis. Most existing clinical treatments involve the use of postoperative chemotherapy for breast cancer, and antidepressant drugs, which treat breast cancer and depression as two independent diseases and have various disadvantages such as low efficiency and strong adverse reactions. Traditional Chinese Medicine (TCM) has a unique value in the prevention and treatment of BCRD via its ability to regulate multiple pathways and targets using multiple components at the same time. In this paper, we review the mechanism of BRCD and the therapeutic mechanisms of TCM from the aspects of neurological disorders, inflammatory immune response, and intestinal flora disorders, with a view to providing references for the clinical application and research of TCM in the treatment of BCRD.

Abstract:Signal transducer and activator of transcription 3 (STAT3) is known to modulate the expression of genes related to cell transformation, proliferation, and survival, making it a significant target for cancer therapy. Recent research has also highlighted the crucial involvement of aberrant STAT3 activation in the pathogenesis of diabetic kidney disease (DKD). Accordingly, this article focuses on the therapeutic potential of targeting STAT3 in DKD. The structure of STAT3, its mechanisms of activity regulation, mechanisms of abnormal STAT3 activation in DKD, and a summary of the current research is provided. The review aims provide a reference for research into the pathogenesis of DKD and the development of new drugs.

Abstract:Cerebral ischemia-reperfusion injury (CIRI) refers to the recovery of blood supply after cerebral ischemia, which leads to further damage and the dysfunction of brain tissue. Modern medicine has made some progress in the prevention and treatment of CIRI, but it still faces some challenges and limitations. Therefore, it is of great clinical value to find effective interventions to prevent and treat CIRI. AMP-activated protein kinase (AMPK) and its downstream proteins are important targets for the treatment of CIRI and play key roles in the regulation of cellular energy homeostasis. Traditional Chinese medicine for CIRI has multi-target and multi-pathway activities and multiple effects. It can activate a cascade of reactions in the AMPK signaling pathway and can be used to treat CIRI by regulating autophagy, oxidative stress, inflammatory response, and apoptosis, and has achieved certain result. Therefore, this paper summarizes the structure and mechanisms of the AMPK-related signaling pathway, elaborates on its relationship with CIRI, and systematically summarizes the research status of traditional Chinese medicine’s ability to regulate the AMPK signaling pathway in the prevention and treatment of CIRI. This paper aims to provide new ideas for the prevention and treatment of CIRI using traditional Chinese medicine and the development of new drugs.

Abstract:Malignant mesothelioma cases are rare and have a long incubation period, making the disease a difficult subject to clinically research. Animal models of malignant mesothelioma are crucial for experimental research and elucidating the pathogenesis of malignant mesothelioma. Common animal models include spontaneous, inducible, transplantable, and genetically engineered models, but the applicability of different animal models varies. This article reviews studies related to the establishment of animal models of malignant mesothelioma published in the past 10 years. Recent progress made in the establishment of four animal models of malignant mesothelioma is summarized from three aspects: modeling method, modeling result, and model advantages and disadvantages. This review summarizes and analyzes the current progress made in the establishment of animal models of malignant mesothelioma and thus provides a reference for basic malignant mesothelioma research using animal models.

Abstract:Vascular dementia (VD) is a neurodegenerative disease caused by brain injury. Research on the processes leading to its occurrence is lacking depth. In recent years, it has been proposed that regulatory cell death (RCD) mechanisms, including apoptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis, are related to the pathological mechanisms of VD. Therefore, studies aiming to explain the links between the mechanisms of regulatory death and the pathology of VD would be beneficial to our understanding of VD. This article provides a review of the roles of five mechanisms of RCD in VD and summarizes the recent progress made in researching the treatment of VD with traditional Chinese medicine, providing a resource for the development of new traditional Chinese medicine drugs.

Abstract:In traditional Chinese medicine, coronary heart disease falls under the categories of “chest impediment and heart pain” and “true heart pain”, with lipid metabolism disorder and the inflammatory response acting as biochemical manifestations of “phlegm and stasis” throughout the disease. The energy metabolism of macrophages is closely related to their immune function and is an important factor in regulating the metabolic disorder and inflammatory responses in coronary heart disease. This article reviews the role of macrophages in the pathophysiology of coronary heart disease. We discuss how these metabolic pathways affect the immune responses of macrophages and influence the disease. We delve into the different modes of macrophage energy metabolism in coronary heart disease, especially the metabolic characteristics and immune regulatory functions of pro-inflammatory M1 and anti-inflammatory M2 macrophages in the syndrome of phlegm and blood stasis. This provides a theoretical guidance for understanding the pathogenic mechanism of the syndrome of phlegm and blood stasis in coronary heart disease and developing new treatment strategies.

Abstract:Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract that poses a significant threat to human health. The pathogenesis of IBD remains unclear and is believed to involve various factors, including genetics, immune dysregulation, and environmental triggers. Recent evidence has highlighted the role of mitochondrial damage and dysfunction in the development of IBD. This article provides a comprehensive review and overview of studies related to the role of mitochondrial damage in IBD, focusing on the effects of mitochondrial oxidative stress damage, autophagy dysfunction, kinetic disturbances, and respiratory defects. The aim is to identify potential therapeutic targets and provide new insights for the scientific prevention and treatment of IBD.

Abstract:Cardiovascular disease presents a serious threat to human life, and oxidative stress has been identified as an important factor affecting the occurrence and development of cardiovascular disease. The construction of reliable animal models of oxidative stress is important for the in-depth study of the pathogenesis of cardiovascular diseases and the development of therapeutic drugs. Zebrafish have often been for research into cardiovascular diseases, due to their advantages of easy reproduction, a short developmental cycle, transparent embryos for easy observation, and a highly homologous cardiovascular genetic background with humans. In this paper, we review the application of the zebrafish oxidative stress model in cardiovascular disease and related research progress, to provide a reference for its further application in cardiovascular disease-related research.