Fitting Degrees of Animal Models of Diarrhea-irritable Bowel Syndrome with Clinical Characteristics of Western Medicine and Traditional Chinese Medicine / 中国实验方剂学杂志

Diarrhea-irritable bowel syndrome （IBS-D） is one of the common functional bowel diseases in clinical practice. Since it pathogenesis is complex and has not been fully elucidated， effective treatment methods remains to be developed for this disease. Establishing the animal models of IBS-D in accordance with the clinical characteristics of traditional Chinese medicine （TCM） and Western medicine helps to reveal the pathogenesis of this disease and improve the treatment plan. The fitting degree of an animal model with clinical characteristics is an indicator to evaluate the effectiveness of the animal model in simulating the disease characteristics of Western medicine and the syndromes of TCM based on the latest diagnostic standards. By reviewing the relevant articles about the animal models of IBS-D， we discovered that rats were the preferred animals for modeling， and the models were mainly induced by single factors， double factors， or the combination of multiple factors. The established animal models mainly present symptoms or signs associated with visceral hypersensitivity or/and gastrointestinal motility abnormalities. The single factor-induced rat models of IBS-D had high fitting degrees with the clinical characteristics of Western medicine but low fitting degrees with the TCM syndromes. The animal models induced by two or more factors had high but varied fitting degrees with the clinical characteristics of Western medicine. In addition， the animal models of IBS-D considering TCM syndromes mainly focuses on the syndrome of liver depression and spleen deficiency， and few models were established for the syndromes of spleen-kidney Yang deficiency， spleen-stomach dampness-heat， spleen deficiency and dampness excess， and cold and heat in complexity. Therefore， it is essential to improve the existing or develop new animal models of IBS-D in the future， so as to provide more tools for deciphering the mechanisms of TCM and Western medicine and developing treatment methods for this disease.

Effect of glutaminase 1 inhibitor on carbon tetrachloride-induced liver fibrosis in mice / 中国生物制品学杂志

@#Objective To investigate the effect of glutaminase 1(GLS1)specific inhibitor BPTES[bis-2-（5-phenylacetamido-1,3,4-thiadiazol-2-yl）ethyl sulfide]on the liver fibrosis in the mouse model of liver fibrosis induced by carbon tetrachloride(CCl4).Methods Male C57BL/6J mice were intraperitoneally injected with olive oil(control group),10%CCl4(10 μL/g,model group)or 10% CCl4(10 μL/g)+ BPTES(10 mg/kg,treatment group),with 10 mice in each group,two doses a week for four weeks to establish liver fibrosis model. Collagen deposition in mouse liver tissue was observed by Sirius red staining. The expression levels of actin alpha 2(Acta2),collagen typeⅠalpha 1(Col1a1)GLS1 and GLS1 protein were detected by qRT-PCR and immunohistochemical staining.Results Compared with the control group,the liver tissue of mice in the model group was generally enlarged,the surface was not smooth and granular,and the ratio of liver mass to tibia length significantly increased(t = 2. 979,P < 0. 05);The Sirius red positive area of collagen deposition increased signifi-cantly in the liver tissue of mice in the model group(t = 7. 661,P < 0. 01),the relative expression levels of Acta2 and Col1a1 significantly increased(t = 4. 335 and 5. 319,respectively,each P < 0. 01),and the mRNA and protein levels of GLS1 significantly increased(t = 5. 319 and 9. 725,respectively,each P < 0. 01). However,compared with the model group,the BPTES treatment group had a reduction in liver mass,a significant reduction in the Sirius red positive area of collagen deposition in liver tissue(t = 7. 427,P < 0. 01),and a significant reduction in the relative expressions of Atca2 and Col1a1(t = 3. 713 and 2. 628,respectively,each P < 0. 05).Conclusion Inhibition of GLS1activity can significantly improve the degree of liver fibrosis induced by CCl4,providing a new idea for the treatment of liver fibrosis.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor / 中国结合医学杂志

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

Effect of Curcumin on Promoting Skin Wound Healing in Diabetes Mice / 医药导报

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

Construction and evaluation of a rat model with blunt contusion of skeletal muscle / 中国康复医学杂志

Objective:To establish a reliable,stable and clinically realistic model of blunt contusion injury to the rat skele-tal muscle. Method:A model of the rat gastrocnemius muscle blunt contusion injury was established by using a weight of 170g,a height of 70cm and a spring with a diameter of 0.5cm at the bottom to buffer the polymeric strik-ing part and guide the fall to hit for 5 consecutive times.The gait changes of rats were evaluated by CatWalk analysis system at 0h,12h,24h,3 days,7 days and 14 days after modeling;local histopathological changes were observed by HE staining and local ultrastructural changes were observed by transmission electron micros-copy.Enzyme-linked immunosorbent assay(ELISA)was used to detect the changes of tumor necrosis factor-α(TNF-α)in local tissues. Result:Compared with the blank group,the mean speed and maximum speed change rate of the model group were significantly decreased,and the difference was statistically significant(P＜0.001);compared with the normal foot group,the maximum contact area,footprint area and standing phase duration of the limb of the injured limb group were significantly decreased,and the difference was statistically significant(P＜0.05).A large infiltration of inflammatory cells and massive lysis necrosis of muscle fibers were observed on HE stain-ing after 3 days.By 14 days,although scar tissue was still present,tissue repair with HE staining was almost indistinguishable from that of the blank group.Vacuolation was observed in part of the sarcoplasmic reticulum at 0h after the blow,and lysis of muscle fibers and part of the sarcoplasmic reticulum at 3 days with in-creased inflammatory response which basically returned to normal by 14 days.The TNF-α level began to rise gradually and reached a peak from 0h to 12h after injury,and remained higher level from 12h to 72h,and the difference was statistically significant compared with the blank group(P＜0.05),and basically returned to the normal level by 14 days. Conclusion:The model can cause moderate damage of skeletal muscle in rats,with a 14-day natural recovery time at least.It can provide as one of the methods for for the establishment of the rat skeletal muscle blunt contusion model.

Effects of different formulations of high-fat diet on establishment of a non-alcoholic fatty liver model in rats / 中国临床药理学与治疗学

AIM:To improve the success rate of experimental modeling of non-alcoholic fatty liver(NAFLD)in rats by high-fat diet through comparing three different formulations of high-fat diets in con-structing non-alcoholic fatty liver rats model,so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease.METHODS:SPF-grade male SD rats were divided into four groups randomly:control group,high-fat diet group1(HFD1),high-fat diet group2(HFD2),high-fat diet group3(HFD3).Each group was given the corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,CT and MRI examination were performed for the rats of each group to check the status.Blood and liver samples were collected.Changes in liver function(ALT,AST),blood lipids(TC,TG,HDL-C,LDL-C),and inflammatory indexes(IL-1β,IL-6,TNF-α)were detected.The morphology of the liv-ers was observed with the naked eyes,and the liv-er index and Lee's index were calculated at the end of 8 weeks.The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups.RE-SULTS:Compared with the control group,rats in the HFD1,HFD2 and HFD3 groups showed poor mental deterioration,decreased activity,severe hair loss,decreased food intake,increased body weights,and significantly increased liver index and Lee's in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared with the control group,the serum levels of ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α were significantly increased,while the contents of HDL-C was significantly decreased in the HFD1,HFD2 and HFD3 group,especially in the HFD3 group.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served in the HFD3 group.CONCLUSION:The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks'feeding,the models induced by HFD3 was better than those in-duced by the other two groups.NAFLD lesion is rel-atively serious and expected to last longer in HFD3 group,which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.

IL2rg-/- rats support prolonged infection of human RSV / 中国实验动物学报

Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0～35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.

Optimization of the azomethane oxide and dextran sodium sulfate model of colitis-associated colon cancer and changes in the intestinal microbiota / 中国实验动物学报

Objective To optimize the method of combining azomethane oxide(AOM)and dextran sodium sulfate(DSS)to create a colitis-associated colon cancer(CAC)model,and to explore the pathogenesis of the intestinal flora in CAC.Methods Model groups A and B were established by one and two injections of AOM,respectively,combined with free drinking of DSS,and a normal control group was injected intraperitoneally with normal saline combined with purified water(n=10 mice per group).The better modeling scheme was selected by comprehensive evaluation of the disease activity index score,colon length,tumor rate,and mortality.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and tumor markers CA199,CEA,and CA724 were detected by enzyme-linked immunosorbent assay.Colon lesions were evaluated by hematoxylin and eosin(HE)staining.Changes in the intestinal microbiota in CAC mice were detected by 16S rDNA high-throughput gene sequencing analysis of mouse feces.Results Both single and enhanced AOM injections combined with DSS induced CAC mice;however,colon growths were larger,more closely arranged,and their morphological size was more consistent in group B compared with group A,with a tumor-formation rate of 100％.IL-6 levels were increased in the model group compared with the normal group(P＜0.05).TNF-α levels were increased in the model group compared with the normal group(P＞0.05).The CA199 and CEA levels were also significantly increased(P＜0.05),but CA724 levels were not.Infiltration of inflammatory cells in the colon detected by HE pathology was accompanied by high-grade intraepithelial tumor-like changes on the surface of the lumen.The diversity and abundance of intestinal bacteria were decreased in CAC mice compared with normal mice:phyla Verrucomicrobiota and Actinobacteriota were significantly increased(P＜0.05),Bacteroidota and Campilobacterota were significantly decreased(P＜0.05).Akkermansia,Prevotellaceae,Ruminococcus,and Bifidobacterium were significantly increased(P＜0.05),and Roseburia,Rikenellaceae_RC9_gut_group,Anaeroplasma,and Muribaculaceae were significantly decreased(P＜0.05).Conclusions Two injections of AOM combined with 1.5％(1.5 g/100 mL)DSS induced CAC model mice with a high colon-tumorigenesis rate,uniform tumor morphology,and low mortality,and may thus be the preferred modeling scheme for pharmacodynamic experiments.Disorders or dysfunction of the intestinal flora may lead to increased permeability,loss of intestinal mucosal barrier function,and the release of enterogenic endotoxins,Resultsing in a sustained inflammatory response,as an indirect or direct cause of CAC pathogenesis.

Research progress on animal models for the evaluation of diarrhea-predominant irritable bowel syndrome / 中国实验动物学报

Irritable bowel syndrome(IBS)is one of the most common functional gastrointestinal disorders,of which diarrhea-predominant IBS(IBS-D)accounts for the largest proportion.The pathogenesis of IBS-D is complicated and diverse,and there is currently a lack of clinically effective drugs.The establishment of animal models is an essential tool for further studies of the disease mechanisms,evaluation of clinical efficacy,and drug development,and the preparation and evaluation standards of models are important factors affecting the quality of the research.Based on the currently accepted pathogenesis of IBS-D and the previous modeling experience of our research group,this review systematically summarizes the evaluation method used in animal models of IBS-D in terms of diarrhea observation,visceral sensitivity tests,and intestinal motility tests,to provide a reference for future studies.

Research progress on animal models of diminished ovarian reserve / 中国实验动物学报

Diminished ovarian reserve(DOR)is associated with a reduced quantity and/or quality of retrieved oocytes,usually leading to low numbers of retrieved oocytes and poor reproductive outcomes.DOR may potentially progress to premature ovarian insufficiency and premature ovarian failure,which have adverse impacts on women's health.There is currently no effective clinical treatment to rescue ovarian function.The limited availability of human ovarian tissues and medical ethics issues mean that animal models are crucial for improving our understanding of the molecular pathogenesis of DOR and identifying preventive and therapeutic targets.This review thus aims to summarize the techniques and strategies used to establish rodent models of DOR,to provide a reference for future studies.

Research progress in evaluation of type 2 diabetic peripheral neuropathy animal model / 中国比较医学杂志

Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.

Analysis of the application characteristics of the acute liver injury animal model based on data mining / 中国比较医学杂志

Objective To investigate the modeling elements of various types of animal models for acute liver injury,and to provide references and suggestions to establish and evaluate animal models of acute liver injury(ALI).Methods The animal experimental literature of ALI from 2002 to 2022 was searched in the databases of the China Knowledge Network,WanFang,Chongqing Vip(VIP),Chinese Medical Journal Full Text Data(Yiigle),and PubMed.The animal species,positive control drugs,modeling method,modeling drugs,and drug administration of the animal models of ALI in the literature were summarized.The result were analyzed using Excel,SPSS Modeler 18.0,and Cytoscape 3.8.2.Results A total of 896 articles were included in the databases.The most used animal models for ALI were male KM mice.The modeling method were mainly chemical liver injury,alcoholic liver injury,drug-related liver injury,and immune liver injury.①The corresponding main modeling method were intraperitoneal injection of 10 mL/kg of 0.1％CC14 in vegetable oil at 24 h before experiments,②gavage of 12.0 mL/kg of 50.0％～56.0％ethanol at 16 h before experiments,③intraperitoneal injection of 300 mg/kg APAP at 24 h before experiments,④tail vein injection of 20 mg/kg Con A at 8 h before experiments.Evaluation of the models was based on liver pathological indexes as the gold standard combined with biochemical indexes of serum ALT,AST,and SOD and MDA contents and activities in liver tissue homogenate as direct indicators.Conclusions Because the causes of ALI vary in clinical practice,the preparation of animal models of ALI should be based on the specific study content and characteristics,and the corresponding modeling method should be selected.

Advances in the application of laser speckle contrast imaging in animal models of chronic cerebral hypoperfusion / 中国比较医学杂志

A visual and quantitative method of dynamically measuring microcirculatory blood flow in a tissue or organ in real time was developed using laser speckle contrast imaging technology.It has been used in numerous microcirculation detection domains because of its benefits of in vivo detection,real-time imaging,and ease of operation.Most animal models of chronic cerebral hypoperfusion involve decreasing blood flow to the brain from bilateral common carotid arteries,which can lead to a protracted deficit in cerebral blood supply.By monitoring and analyzing cortical cerebral blood flow,collateral circulation opening,and neurovascular coupling responses,laser speckle contrast imaging technology assesses the efficacy of modeling and the therapeutic effect of interventions in animal models of chronic cerebral hypoperfusion.This article summarizes the benefits and drawbacks of laser speckle contrast imaging in an animal model of chronic cerebral hypoperfusion to promote novel approaches to clinical care and academic study.

Establishment and Evaluation of A High-Speed Fragment-Induced Penetrating Liver Injury Model Assisted by Portable Ultrasound / 中国医学影像学杂志

Purpose To establish and evaluate a high-speed fragment-induced penetrating liver injury model in pigs assisted by portable ultrasound.Materials and Methods With the aid of portable ultrasound,the lower edge of the liver at the end of expiration and the lower edge of the right chest at the end of inspiration of 10 Landrace pigs were positioned on the body surface.Then the sighting line was traced to determine the direction of projection and the sighting point.High-speed(about 627 m/s)fragments were projected through an experimental ballistic gun to induce penetrating liver injury.Blood pressure,heart rate,respiratory rate,pulse oxygen saturation and other physiological indexes were measured 15 minutes before shooting and 20 minutes after shooting.20 minutes after injury,the liver injury and the degree of injury were examined by ultrasound.After injury,the liver injury and abdominal fluid accumulation were observed by on-site portable ultrasound,and the size of liver trauma,liver injury grade,abdominal fluid accumulation location and maximum depth were recorded.The degree of liver injury was evaluated by comparison with the gross pathological results.Results Nine out of ten pigs were successfully modeled.The success rate of penetrating liver injury induced by fragments was 90%(9/10),other organ injury in abdominal cavity was 22.22%(2/9),and diaphragm penetrating injury was 22.22%(2/9),which did not occur obvious hemopneumothorax.After injury,the systolic blood pressure,diastolic blood pressure,and pulse oxygen saturation of the pigs decreased[(132.44±12.65)mmHg vs.(103.33±33.43)mmHg,(96.44±12.27)mmHg vs.(70.89±24.21)mmHg,(89.44±8.49)%vs.(76.00±13.41)%;t=2.440,2.651,4.084,all P<0.05],and the heart rate increased[(94.00±17.39)times/min vs.(139.89±37.21)times/min;t=3.534,P<0.05].Within 20 minutes after modeling,portable ultrasound images showed that the liver injury was a patchy,heterogeneous,slightly strong echo area with clear and irregular boundary,and the continuity of the local liver capsule was interrupted.The ascites appeared in the abdominal cavity with the maximum depth of(4.16±1.35)cm.The American association for the surgery of trauma(AAST)liver injury grading of gross pathology after the animals were killed showed that there were 6 cases of grade Ⅱ and 3 cases of grade Ⅲ.Along the fragment projection direction,the short diameter measured by ultrasound was positively correlated with the depth of gross pathological laceration(r=0.945,P<0.001).Compared with the gross specimen,the accuracy rate of ultrasonic AAST grading of liver injury was 88.89%(8/9).Conclusion The model of high-speed fragment-induced liver injury in pigs assisted by portable ultrasound is accurate and stable,and portable ultrasound can effectively evaluate the penetrating liver injury,which provides a basis for the treatment of liver firearm injury.

Analysis of Animal Models of Post-infectious Irritable Bowel Syndrome Based on Characteristics of Clinical Symptoms of Traditional Chinese and Western Medicine / 中药新药与临床药理

Objective This paper summarizes and evaluates the existing animal models of Post-infectious irritable bowel syndrome(PI-IBS)based on the clinical diagnostic criteria and symptom characteristics of PI-IBS in Chinese and western medicine.The goal of this study is to seek out animal models with a high degree of clinical agreement between Chinese and western medicine,and to provide an accurate animal model for the prevention and treatment of PI-IBS in traditional Chinese medicine.Methods The animal strains,modelling methods,and mechanisms of the existing PI-IBS animal models were summarized based on the clinical diagnostic features and symptomatology of PI-IBS,as well as the degree of match was evaluated and the strengths and weaknesses of the preparation of animal models were analyzed,by reviewing the articles related to PI-IBS animal experiments and the preparation of animal models.Results A thorough analysis discovered that Campylobacter jejuni infection model,Trichinella infection model,and liver depression and spleen deficiency syndrome in models of disease and symptom combination showed a comparatively high level of clinical agreement between Chinese and western medicine.Conclusion The existing PI-IBS models had the high degree of coincidence with western medicine,Chinese medicine four diagnoses and syndrome are generally less embodied and collected in the modeling process.The primary symptoms in Chinese medicine diagnosis are primarily based on the observation of animal apparent behaviors,while the observation of the sub-syndrome manifestations is relatively less,which results in failure of judgment of TCM syndrome types.Therefore,it is still necessary to further standardize the criteria for evaluating symptoms and the techniques for identifying disease-syndrome combination animal models.PI-IBS model with the syndrome-clinical characteristics in Chinese and western medicine has significant application value and prospects in the future.The multifactorial composite method of western medicine pathological injury+Chinese medicine etiological stimulation can establish a PI-IBS model with a higher degree of coincidence,which can provide theoretical support for the study of the pathogenesis of PI-IBS,the difference of syndrome,and the prevention and treatment with integrative Chinese and western medicine.It is crucial to guide the clinical diagnosis and treatment of PI-IBS.

Visual Analysis of Research Trends and Hotspots in Animal Models of Chronic Heart Failure / 中药新药与临床药理

Objective To understand the research situation of animal model of chronic heart failure(CHF)based on visualization software and bibliometrics methods,and to explore the research hotspots of animal models of CHF and guide the design of animal experiments and scientific research.Methods Literature related to animal model of CHF included in Web of Science core collection from January 1,2001 to October 10,2022 were retrieved.After reading the full text and obtaining the final included literature,VOSviewer and CiteSpace software were used to analyze the contents of institutions,journals and co-cited journals,authors and co-cited authors,keywords.Results A total of 961 papers were included,and the number of published papers increased steadily.The United States and China are the main research countries.Johns Hopkins University and Harvard University are major research institutions.The most frequently published and cited journals are AM J PHYSIOL-HEART C and CIRCULATION,etc..Schultz Harold D and Sabbah Hani N are more influential in author selection."Myocardial infarction","cardiac hypertrophy",and"rat"are the most frequent keywords,10 clusters and 18 emergent words were formed.Conclusion The research in this field is numerous,high quality but scattered.Commonly used animal models are rodents and dogs.The main modeling methods are surgery and drugs.The main pathological mechanisms are mainly myocardial hypertrophy,oxidative stress,and myocardial fibrosis.

Establishment of mitral regurgitation model by a transapical artificial chordae tendineae implantation device in swines / 中国胸心血管外科临床杂志

@#Objective To research the procedure for creating an animal model of mitral regurgitation by implanting a device through the apical artificial chordae tendineae, and to assess the stability and dependability of the device. Methods Twelve large white swines were employed in the experiments. Through a tiny hole in the apex of the heart, the artificial chordae tendineae of the mitral valve was inserted under the guidance of transcardiac ultrasonography. Before, immediately after, and one and three months after surgery, cardiac ultrasonography signs were noted. Results All models were successfully established. During the operation and the follow-up, no swines died. Immediately after surgery, the mitral valve experienced moderate regurgitation. Compared with preoperation, there was a variable increase in the amount of regurgitation and the values of heart diameters at a 3-month follow-up (P<0.05). Conclusion In off-pump, the technique of pulling the mitral valve leaflets with chordae tendineae implanted transapically under ultrasound guidance can stably and consistently create an animal model of mitral regurgitation.

Preparation Methods and Evaluation Criteria Analysis of Animal Models for Perimenopausal Syndrome / 实验动物与比较医学

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.MethodsIn 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.

Advances in Research on Pathological and Molecular Mechanism of Hyperuricemic Nephropathy Based on Animal Models / 实验动物与比较医学

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.

Advances in Comparative Medical Research on Anatomy and Histological Structure of Intervertebral Discs in Humans and Other Animals / 实验动物与比较医学

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.