Abstract: Objective To establish a model of glycolipid metabolic disorder model in Zucker diabetic fatty (ZDF) rats induced by Purina 5008 feed, and to evaluate its pathological characteristics to provide a preclinical model tool for mechanistic research and drug development. Methods Twelve-week-old male ZDF rats were selected as the model group and Zucker lean(ZL) rats served as the normal control group (n= 9 rats per group). Rats in the model group were fed Purina 5008 feed, while normal control rats received standard feed for 7 weeks. Observations included physical sign scores, body mass, Lee’ s index, food and water intake, fasting blood glucose, oral glucose tolerance, serum total cholesterol ( TC), triglycerides ( TG), low-density lipoprotein cholesterol ( LDL-C), high-density lipoprotein cholesterol ( HDL-C), alanine aminotransferase ( ALT), aspartate aminotransferase ( AST),insulin levels, and homeostasis model assessment of insulin resistance ( HOMA-IR). Pathological changes in the liver, pancreas, and aorta were analyzed by hematoxylin-eosin(HE) and oil red O staining. Results Compared with the normal control group, model rats showed typical signs such as excessive drinking and eating, dull hair ( P<0. 01), and their body mass, Lee’s index, food / water intake increased significantly (P<0. 01), and fasting blood glucose, blood lipid and HOMA-IR all increased significantly (P<0. 01). Pathological examination revealed severe hepatic steatosis, vacuolar degeneration of pancreatic islet cells, and disorganized aortic wall structure with uneven thickening in the model group. Conclusions A ZDF rat model induced by Purina 5008 feed can stably simulate the core pathological features of glycolipid metabolic disorders, including metabolic dysregulation, insulin resistance, and multi-organ damage, offering a reliable platform for future mechanistic studies and therapeutic evaluation.

Abstract: Objective To compare the effects of different dietary intervention regimens and the combined effect of metformin after the establishment of a type 2 diabetes mellitus (T2DM) model, to establish and maintain a T2DM rat model that is more consistent with clinical practice. Methods Fifty male SD rats were divided randomly into control (n= 10) and model groups ( n= 40). Rats in the model group were fed a high-sugar and high-fat (HSHF) diet, plus daily intragastric administration of fat emulsion starting from the 3rd week. After 4 weeks, T2DM was induced by two intraperitoneal injections of streptozotocin 25 mg / kg. After successful model establishment, rats in the model group were divided randomly into four subgroups ( n= 10 rats per group): HSHF model ( HSHF-M),normal diet model (ND-M), HSHF metformin (HSHF-Met), and normal diet metformin groups (ND-Met). Rats in the drug-treated groups received dietary intervention combined with metformin, while rats in the model groups received dietary intervention alone, and rats in the control group were fed a normal diet. All interventions lasted for 12 weeks. The general status of the rats and their survival indicators were monitored during the dietary-intervention period. After 12 weeks, an oral glucose tolerance test (OGTT) was performed. Serum fasting insulin ( FINS) was detected to calculate the insulin resistance index (HOMA-IR) and islet β-cell function index (HOMA-β). Serum levels of blood lipids, liver function, renal function, oxidative stress indicators, and inflammatory factors were also measured and pathological changes in the pancreas, liver, and kidney tissues were observed and analyzed. Results After successful establishment of a T2DM rat model, feeding with a normal diet maintained model stability within 12 weeks. Compared with the HSHF-M group, rats in the ND-M group had significantly increased body mass (P<0. 05) and significantly decreased urine output and blood glucose (P<0. 05). Regarding the OGTT, blood glucose levels at 0,30, 60, and 120 min were significantly lower in the ND-M compared with the HSHF-M group and the area under the curve was significantly reduced ( P<0. 05). Regarding blood glucose-related indicators, there were significant differences in glycated serum protein, FINS, and HOMA-IR (P<0. 05). For blood lipid-related indicators, total cholesterol, triglycerides, free fatty acids, and low-density lipoprotein cholesterol levels were all significantly decreased (P<0. 05), while high-density lipoprotein cholesterol was significantly increased (P<0. 05) in the NDM group. Liver function-related indicators (alanine transaminase, alkaline phosphatase, aspartate transaminase) and renal function-related indicators (creatinine, blood urea nitrogen) were significantly decreased (P<0. 05), while nitric oxide levels were significantly increased (P<0. 05) in the ND-M group. Regarding oxidative stress indicators, malondialdehyde levels were significantly decreased (P<0. 05) and superoxide dismutase was significantly increased (P<0. 05) in the ND-M group. Levels of inflammatory factors (tumor necrosis factor-α, IL-1β) were significantly decreased (P<0. 05) in the ND-M group. Histopathological changes, such as hepatic cord disorder, islet cell reduction, and glomerular vacuolation, were significantly alleviated in the ND-M group, in the absence of long-term intake of an HSHF diet, compared with the HSHF-M group. Survival and biochemical indicators were significantly improved in the HSHF-Met and ND-Met groups compared with the HSHF-M group in ( P<0. 05), with a more significant improvement in the ND-Met group while pathological damage to the pancreas and liver was less severe than in the HSHF-Met group. Conclusions Feeding a normal diet after establishment of a T2DM model can effectively avoid glucose and lipid metabolism disorders, oxidative stress, inflammatory responses, and multi-organ pathological damage caused by a HSHF, thereby allowing the successful establishment and maintenance of a T2DM rat model that is more consistent with clinical pathways.

Abstract: Objective This study aimed to investigate the impact of sciatic nerve transection on the gut microbiota in mice by establishing a sciatic nerve injury model and analyzing changes using 16S rRNA gene sequencing. Methods Eighteen C57BL / 6 mice were randomly divided into six groups: sham-operated(sham), and experimental groups(postoperative Day 1 (D1), Day 4 (D4), Day 7 (D7), Day 14 (D14), and Day 28 (D28) groups). Colonic contents were collected at different time points after model induction for 16S rRNA sequencing to assess alterations in microbial composition and predict functional changes in the gut microbiome. Results A clear temporal shift in the gut microbial community structure was observed following sciatic nerve transection. From Day 4 post-surgery, microbial richness and diversity showed a significant decline, indicating a disturbance in microbial homeostasis. By Day 7, partial recovery in community richness was noted, suggesting a transient adaptation phase.Taxonomic analysis revealed significant fluctuations in the relative abundance of dominant bacterial phyla, particularly Firmicutes, Verrucomicrobiota, and Proteobacteria. At the genus level, the abundance of Akkermansia progressively declined over time in the experimental groups compared to the sham group, while Kurthia and Dubosiella demonstrated a notable increase starting on Day 4 and peaking on Day 7. These dynamic changes imply specific microbial taxa are responsive to peripheral nerve injury. Furthermore, microbial functional prediction suggested that several metabolic pathways, including lipid and amino acid metabolism, may be affected after sciatic nerve transection in mice. These findings suggest a close association between nerve injury and gut microbial functional attenuation. Conclusions Sciatic nerve transection induced significant alterations in the gut microbiota composition of mice, accompanied by changes in metabolism-related pathways as predicted by functional gene analysis. These findings suggest that the potential functions of gut microbes may be affected. Further validation through metabolomic analysis is required,which may provide valuable insights into the potential role of gut microbiota in peripheral nerve injury repair.

Abstract: Objective To establish a mouse model of hepatocellular carcinoma pain by implanting hepa1-6 tumor tissue in the left liver lobe, and to evaluate the effectiveness of the model using behavioral, imaging,histological, and molecular biological indicators. Methods Hepa1-6 cell suspension (100 ~ 150 μL, 4 × 10⁶cells/mL) was inoculated subcutaneously in the axillary region of the forelimb. Resulting tumors were removed and cut into tissue blocks (about 1 mm × 1 mm × 1 mm) when they protruded from the body surface. SPF male C57BL / 6J mice were divided randomly into sham-implantation (sham) and model groups (n = 30 mice per group). Model mice were implanted with hepa1-6 tumor tissue blocks in the left liver lobe, while sham mice received no implant after laparotomy. General activity, body mass, and behavior in relation to back pain were evaluated. Gross liver morphology was examined by ultrasound. The structure, cell composition, and inflammatory cell infiltration of liver tissue was observed by hematoxylin-eosin (HE) staining. Activation of microglia in the spinal cord tissue was detected by immunohistochemistry ( IHC). mRNA expression of interleukin ( IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in the spinal cord was detected by quantitative polymerase chain reaction ( qPCR), and IL-1β protein expression was detected by Western Blot. Results The general conditions of mice in the model group were abnormal, body mass was decreased, and the arched back pain score was significantly increased compared with the sham group (P<0. 05). Ultrasound revealed protruding liver tumor tissues in the model group, and HE staining showed abnormal liver tissue structure with numerous tumor cells and inflammatory cells in the model group. Spinal cord expression of Iba1 protein detected by IHC, IL-1β, IL-6, and TNF-α mRNA expression detected by qPCR, and protein expression of IL-1β detected by Western Blot were all significantly increased in the model group (P<0. 05). Conclusions A mouse model of hepatocellular carcinoma pain can be effectively established by implanting hepa1-6 tumor tissues in the left liver lobe. The resulting model mice show abnormal behavior in relation to back pain, abnormal liver morphology and structure, and activation of pain and inflammatory factors. This thus provides an effective animal model for the study of hepatocellular carcinoma pain, and an effective means for studying the pathogenesis of hepatocellular carcinoma pain and the effects of drug treatment.

Abstract: Objective To determine if saikosaponin D (SSD) alleviates renal injury and fibrosis in chronic kidney disease ( CKD) models by regulating the long non-coding RNA-gm33782 ( LncRNA-gm33782), thereby modulating the glycolysis pathway. Methods A CKD model was established in C57BL / 6 mice using unilateral ureteral obstruction (UUO). Thirty mice were assigned randomly to sham group, UUO group, SSD-L group(30 mg / kg), SSD-H group (60 mg / kg), and Irb group(20 mg / kg) (n = 6 mice per group). After oral administration for 7 d, the mice were euthanized and kidneys harvested. Renal pathological injury was assessed using hematoxylin-eosin (HE), Masson, and Sirius red staining. Fibrosis markers ( fibronectin ( FN), α-smooth muscle actin( α-SMA),collagen 1 (Col-Ⅰ)) were detected by immunohistochemistry and Western Blot. LncRNA-gm33782 expression was quantified by RT-qPCR. Renal lactate concentration was measured and hexokinase 2 (HK2) protein expression was assessed by Western Blot to evaluate associations between LncRNA-gm33782 and renal fibrosis and glycolysis. An in vitro fibrosis model was induced in mouse renal tubular epithelial cells ( TCMK-1) by transforming growth factor (TGF)-β induction. Knockdown and overexpression of LncRNA-gm33782 were employed to assess its effects on fibrosis markers ( FN, Col-Ⅰ), glycolysis-associated proteins ( HK2, pyruvate kinase M2), and mitochondrial function ( cellular oxygen consumption rate, OCR ). SSD intervention was applied under LncRNA-gm33782- overexpression conditions to evaluate its protective effects. Results SSD significantly attenuated renal tissue injury,fibrosis, and lactate accumulation in UUO mice. LncRNA-gm33782 was significantly upregulated in in vivo (UUO) and in vitro fibrosis models ( P<0. 05 ). SSD reduced LncRNA-gm33782 expression ( P<0. 05 ). In vitro knockdown of LncRNA-gm33782 ameliorated TGF-β-induced cellular fibrosis and suppressed glycolytic activation,while its overexpression exacerbated mitochondrial OCR suppression, fibrosis, and glycolytic activation, and attenuated the protective effects of SSD ( P<0. 05). Conclusions SSD alleviates renal fibrosis primarily by targeting and suppressing LncRNA-gm33782 expression, leading to downregulation of glycolytic activation and restoration of mitochondrial function. LncRNA-gm33782 is a key molecular target mediating the renoprotective effects of SSD.

Abstract: Objective To construct an animal model of type 2 diabetic nephropathy (DN) combined with the disease and syndrome of “ dampness syndrome” in traditional Chinese medicine, and to conduct a macroscopic characterization and microscopic index evaluation of the model. Methods Spontaneous db / db mice were fed a 60% high-fat diet to create internal dampness syndrome and construct an animal model of DN combined with damp syndrome ( TSSZ ). The general condition, body mass, and biochemical indicators ( urinary microalbumin-tocreatinine ratio, blood glucose, renal function, glucose and lipid metabolism) were monitored in each group of mice.Pathological changes in the kidney were observed by hematoxylin-eosin (HE), periodic acid-schiff (PAS), Masson,and Oil red O staining. Renal microinflammation and fibrosis were detected by polymerase chain reaction (PCR) and the degree of macrophage polarization in renal tissue was detected by immunofluorescence assay. The mucosal barrier of intestinal tissue was examined by HE staining and PCR. Mouse feces were collected and the fecal metabolome was determined using liquid chromatography / mass spectrometry. Results The unrinary microalbumin-to-creatinine ratio was increased in the model group compared with the control group( P<0. 05). HE and PAS staining indicated significant homogeneous thickening of the glomerular basement membrane and proliferation of the mesangial matrix in the model group, and PAS staining showed a significant increase in glycogen deposition (P<0. 05), which met the criteria for successful construction of a DN model. Macroscopically, compared with the model group, mice in the TSSZ group presented obvious symptoms such as greasy and oily skin and hair, loose stools, listlessness, fatigue, huddling and curling up, polyuria, and significantly increased body mass ( P<0. 05). In terms of lipid toxicity indicators, total cholesterol levels were significantly elevated in the TSSZ group ( P<0. 05). Oil red O staining showed significant lipid droplet deposition, and Masson staining indicated obvious blue staining of collagen and aggravated fibrosis in the glomerular interstitium in the TSSZ group (P<0. 001). mRNA levels of the pro-fibrotic factors α-smooth muscle actin, connective tissue growth factor, fibronectin, and transforming growth factor-β were significantly increased (P<0. 001), and in terms of microinflammation, levels of the inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6 were significantly elevated in the TSSZ group (P<0. 001), and polarization of M1-type macrophages was significantly enhanced ( P<0. 05). In terms of intestinal microecology, HE staining indicated aggravated intestinal injury in the TSSZ group. mRNA levels of intestinal ZO-1 and occludin were significantly decreased in the TSSZ group ( P<0. 001). Fecal metabolomics analysis showed that dampness syndrome modeling affected related metabolic pathways, including α-linolenic acid and tryptophan metabolism. Conclusions Feeding spontaneous db / db model mice with a 60% high-fat diet can successfully create a type 2 DN combined with dampness syndrome disease model. This provides an ideal animal model for further in-depth studies into the construction of a type 2 TSSZ animal model, as well as the pharmacodynamics of Chinese herbal compounds in DN.

Abstract: Objective To investigate the effects of Radix Tetrastigma hemsleyani flavone ( RTHF) on pyroptosis and ferroptosis in mice with sepsis liver injury via activation of the Nrf2 signaling pathway and its molecular mechanism. Methods KM mice were divided randomly into six groups: a control group, model group, positive control group (dexamethasone 10 mg / kg) and low, middle and high dose RTHF groups. Mice in the RTHF groups were pretreated with intraperitoneal injections of 60, 90 and 120 mg / kg RTHF for 7 d, while mice in the positive control group were pretreated by intraperitoneal injection of dexamethasone 10 mg / kg for 7 d. An acute liver injury model of sepsis was established by intraperitoneal injection of lipopolysaccharide ( 10 mg / kg ). The mice were euthanized 24 h later and liver and blood samples were collected. The therapeutic efficacy and pharmacological mechanism of RTHF against sepsis-induced acute liver injury were evaluated by observations of gross specimens,histopathology, biochemical examination, and molecular biology examinations. Results Compared with the model group, low, middle and high dose RTHF groups significantly reduced serum levels of alanine transaminase(ALT), aspartate aminotransferase(AST), interleukin (IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and IL-18 and liver levels of malondialdehyde(MAD), Fe^{2 +}, and reactive oxygen species(ROS) (P<0. 01, P<0. 05), significantly increased liver superoxide dismutase(SOD) and glutathione(GSH) levels (P<0. 01, P<0. 05), improved liver tissue pathology and inflammatory infiltration, and decreased the liver index. RTHF also up-regulated the expression of Nrf2 protein, Nrf2 and heme oxygenase-1(HO-1) levels in the nucleus, and solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase-4 protein(GPX4) expression (P<0. 01, P<0. 05), and down-regulated the expression of Cleaved-Caspase-1, GSDMD-NT, as well as Keap1, NLRP3, Caspase-1, Cleaved-Caspase-1,GSDMD and GSDMD-NT (P<0. 01, P<0. 05). Conclusions RTHF can reduce the release of inflammatory factors, relieve oxidative stress, inhibit ferroptosis and NLRP3-mediated pyroptosis by activating the Nrf2 signaling pathway, and may thus have protective effects against lipopolysaccharide-induced hepatic injury in mice with sepsis.

Abstract: Objective To establish an experimental method for determining the glycemic index (GI) in honey-containing herbal preparations in mice. Methods With reference to the WS / T 652-2019 standard, the experimental method for mouse testing was optimised. Samples comprising fructose / glucose syrups at varying ratios were employed to validate the feasibility of the preliminary conditions. The optimised method was applied to the determination of the GI of honey and the traditional Chinese medicinal preparation containing honey-Guhan Nutritive Essence. Results Under the optimized conditions, the GI values of fructose / glucose syrup were closest to the theoretical values, and the correlation with the fructose ratio was highly linear (R²= 0. 9959). The GI values of the four honeys with different fructose / glucose ratios were 60. 3, 54. 3, 56. 5, and 59. 3, respectively, which were lower than those of fructose / glucose syrups with the same ratios. The GI values of the honey-containing herbal preparation Guhan Nutritive Sample ranged from 45. 2 to 59. 6, and decreased with decreasing honey GI. Conclusions This optimized mouse assay is expected to provide an effective tool for determining the GI of honey-containing herbal preparations and for screening honey raw materials.

Abstract: Objective To investigate the inhibitory effect of Poecilobdella manillensis ( PM) extract on kappa-carrageenan (KCG)-induced tail thrombosis in mice. Methods KM mice were treated with intraperitoneal PM extract JC-17 (2. 5, 25, or 100 mg / kg) or heparin sodium (50 mg / kg) for 7 consecutive days. Tail thrombosis was induced 1 hour after the last dose by injection of 0. 5% KCG. Results The tail-blackening rate in the model group (mice were treated with 0. 2 mL of 0. 5% KCG) at 48 h was ( 94. 91 ± 3. 93)%, confirming successful induction of thrombosis. Mice in the PM-treated groups ( L, M, H) exhibited dose-dependent reductions in tail blackening. The extract significantly prolonged the prothrombin time ( PT) and reduced fibrinogen ( FIB) levels.Splenic levels of tumor necrosis factor (TNF)-α, interleukin-1β(IL-1β), and interleukin-6(IL-6) were elevated in the model group. All PM-treated groups and PC group showed significant suppression of these inflammatory cytokines. Conclusions PM extract JC-17 effectively inhibits KCG-induced tail thrombosis and exhibits anti-inflammatory activity, suggesting its potential therapeutic value for inflammation-associated thrombotic disorders.

Abstract:Pancreatic cancer (PC) is highly malignant, with an insidious onset and poor prognosis. Current treatment measures often fail because of the immunosuppressive characteristics of the tumor microenvironment (TME), leading to recurrence and resistance. The characteristics of the TME frequently affect the efficacy of tumor immunotherapy, especially in suppressive immune microenvironments, where immune evasion and immune tolerance of the tumor commonly occur. The progression of PC result from the combined effects of the microbiota, the host’ s genetic background, and environmental factors. The microbiota plays a central regulatory role by reshaping the immune microenvironment, and targeting specific microbiota to modulate immune cell function can enhance the efficacy of immune checkpoint inhibitors. This review focuses on the immune microenvironment in PC, analyzing the differences in microbiota associated with gastrointestinal tumors, and summarizes research progress on the mechanisms by which the microbiota influences the PC immune microenvironment and enhances the effectiveness of immunotherapy. The review also examines the potential of the microbiota and its metabolic pathways for improving the suppressive immune microenvironment in PC, and discusses the regulatory mechanisms of the microbiota in PC immune responses, aiming to provide new personalized immunotherapeutic strategies for patients with PC.

Abstract:Animal models of cataracts provide essential tools for investigating the pathological mechanisms and evaluating pharmacological interventions. The precision of lens-opacity grading is contingent upon the congruence between anatomical characteristics and the grading system used. Current clinical grading frameworks are primarily based on human ocular anatomy; however, there are notable anatomical disparities among animal species. For instance, the lens diameter in mice is approximately (1. 2 ± 0. 1) mm, compared with (8. 5 ~ 9. 5) mm in humans, with mice having a relatively smaller nuclear region. Similarly, the corneal curvature in rabbits is (7. 2 ± 0. 1) mm compared with ( 8. 0 ± 0. 2 ) mm in humans, and the zebrafish lens lacks the conventional nucleus-cortex differentiation observed in mammals. These anatomical differences contribute to issues such as dimensional redundancy, detection bias, and grading distortion when applying human-based clinical grading systems to animal models. This review examines various method for inducing cataracts in animal models, systematically evaluates how the above anatomical variations affect the suitability of existing grading systems, and proposes tailored strategies to enhance grading accuracy. Specifically, we recommend employing a modified lens opacities classification system Ⅲ (LOCSⅢ) or a simplified grading approach for mice, developing a grading system focused on nuclear opacity for rabbits, and utilizing grayscale-quantification techniques for zebrafish. These customized method ologies aim to establish more precise grading standards to support cataract research utilizing animal models.

Abstract:Animal models of hyperuricemia are widely used in relevant research; however, there is currently a lack of standardized preparation and evaluation protocols. Based on a comprehensive review of the domestic and international literature, this article summarizes and analyzes the current applications of hyperuricemia animal models. It systematically categorizes the selection criteria for commonly employed animal models in hyperuricemia studies, with a particular focus on the critical analysis of induced animal modeling method ologies. The findings aim to provide a reference framework for establishing reliable hyperuricemia animal models with enhanced pathophysiological relevance.

Abstract:Postoperative cognitive dysfunction ( POCD) is a prevalent complication affecting the central nervous system following anesthesia and surgery in elderly patients. It is characterized by a multidimensional decline in cognitive function, which significantly extends hospital stays and increases both medical and social burdens. Recent studies have identified the inhalational anesthetic sevoflurane as a significant contributing factor to the onset of POCD. This systematic review considers the strategies used to construct animal models of sevoflurane-induced POCD and explores its multifaceted mechanistic pathways. The analysis focuses on six dimensions: neuroinflammation,mitochondrial dysfunction, synaptic plasticity impairment, tau protein phosphorylation, abnormal epigenetic regulation, and alterations in blood-brain barrier (BBB) permeability. Empirical evidence indicates that sevoflurane can induce cognitive impairment by activating microglia, upregulating pro-inflammatory factors inhibiting mitochondrial complex Ⅰ/ Ⅲ function, inducing oxidative stress, disrupting the expression of synaptic structural proteins, promoting excessive phosphorylation of tau protein, and inducing hypermethylation of promoters of key genes such as brain-derived neurotrophic factor( BDNF), along with histone deacetylation. Furthermore, sevoflurane can compromise the integrity of the BBB under specific pathological conditions, exacerbating the infiltration of peripheral inflammatory factors into the central nervous system and establishing a positive feedback loop between neuroinflammation and cognitive impairment. Sevoflurane induces POCD via a synergistic network involving multiple pathways. Future strategies should transition from single-target to multi-pathway interventions to protect postoperative cognitive function in older adult patients.

Abstract:Gastric cancer is a highly prevalent malignant tumor worldwide that typically progresses through a precancerous lesion stage, including chronic atrophic gastritis, intestinal metaplasia, and dysplasia. Mouse models of gastric precancerous lesions have recently played a significant role in studies examining the mechanisms of gastric carcinogenesis, its pathological features, and drug interventions. This article systematically summarizes the research progress in animal models of gastric precancerous lesions, including spontaneous, chemically induced, transgenic,infection, diet-induced, cell transplantation, and radiation-induced models. By simulating the histological features (e. g. , glandular atrophy, intestinal metaplasia) and molecular biological characteristics (e. g. , activation of nuclear factor-κB(NF-κB) and Wnt / β-catenin signaling pathways, role of inflammatory mediators) of gastric precancerous lesions, these models provide a multidimensional experimental platform for studying the pathogenesis of gastric cancer. Furthermore, model studies have revealed close associations between gastric precancerous lesions and various pathogenic factors, such as Helicobacter pylori infection, gene mutations, and chemical carcinogens. Existing models,however, still have certain limitations in terms of replicating the complexity, genetic heterogeneity, and tumor microenvironment of human gastric precancerous lesions. This review provides a comprehensive reference for the selection and application of gastric precancerous lesion models, providing important theoretical support for basic research and clinical translation in gastric cancer.