ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate （Glu）/γ-aminobutyric acid （GABA）. Methods48 Sprague-Dawley （SD） adult rats were randomly divided into the sham operation group， model group， Yishen Huoxue Tongqiao Formula groups with low， medium， and high doses （9.20， 18.39， 36.78 g·kg^-1）， and betahistine group （1.62 mg·kg^-1）. A unilateral vestibular labyrinth destruction （vestibular dysfunction） model was established by intratympanic injection of chloroform into the right ear， while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period， behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei （NeuN）， growth-associated protein 43 （GAP-43）， and glial fibrillary acidic protein （GFAP）. Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were applied to determine the expressions of glutamate-immunoreactive （Glu-IR）， GABA， GFAP， postsynaptic density protein 95 （PSD-95）， and GAP-43. ResultsCompared with the sham operation group， the model group presented with head deviation， balance disorder， increased tail suspension score， nuclear consolidation of medial vestibular nerve neurons， and decreased Nissl bodies （P<0.01）. The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased （Glu/GABA decreased）. The expression of GAP-43 was down-regulated， and GFAP was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PSD-95， and GAP-43 proteins， as well as Glu-IR mRNA decreased， while the expressions of GABA and GFAP proteins and mRNA increased （P<0.05， P<0.01）. Compared with those in the model group， the head deviation， imbalanced behavior， and tail suspension scores in each treatment group decreased， with alleviated neuronal injury and recovered Nissl bodies （P<0.01）. The number of dendritic spines of neurons increased， and the number of NeuN-positive cells rebounded. The content of Glu increased， and the content of GABA decreased （Glu/GABA increased）. GFAP was down-regulated， and GAP-43 was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PMD-95， and GAP-43 proteins， as well as Glu-IR mRNA increased， while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group （P<0.01）. ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction， and its mechanism may be associated with regulating the metabolic balance of Glu/GABA， mitigating neural damage， improving synaptic plasticity （promoting GAP-43 expression and inhibiting GFAP expression）， and facilitating vestibular compensation.

OBJECTIVE To analyze the differences in chemical components of Gardenia jasminoides before and after processing with ginger， and to evaluate the quality differences among different producing areas. METHODS Ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry was used to analyze the compositional differences of G. jasminoides before and after processing with ginger. The water content， total ash， and ethanol-soluble extract content of ginger- processed G. jasminoides were determined according to the 2020 edition of Chinese Pharmacopoeia. High performance liquid chromatography was adopted to determine the contents of genipin gentiobioside， geniposide， crocin Ⅰ and crocin Ⅱ in ginger- processed G. jasminoides. RESULTS A total of 49 chemical components were identified from raw G. jasminoides and ginger- processed G. jasminoides， including 14 flavonoids， 15 iridoids， 10 organic acids， 2 alkaloids and 8 other compounds. Among them， 42 components were detected in raw G. jasminoides， 28 in ginger-processed G. jasminoides， and 21 components were common to both. After processing with ginger， raw G. jasminoides lost 21 components （including iridoids， flavonoids， alkaloids， and others）， while 7 chemical components were added （including coumarins， organic acids， organic acid esters， and flavonoids）. For the 15 batches of ginger-processed G. jasminoides， the water content ranged from 5.64% to 7.11%， total ash from 2.92% to 4.87%， and ethanol-soluble extract from 40.61% to 58.02%. The average contents of genipin gentiobioside， geniposide， crocin Ⅰ and crocin Ⅱ were 0.108 7， 0.542 2， 0.565 0， and 0.012 5 mg/g， respectively. CONCLUSIONS After processing with ginger， G. jasminoides loses 21 components， while 7 new components are added. Differences are observed in the water content， total ash， ethanol-soluble extract， and the contents of genipin gentiobioside， geniposide， crocin Ⅰ， and crocin Ⅱ of ginger-processed G. jasminoides from different producing areas. Notably， samples from Fujian exhibit high contents of genipin gentiobioside and ethanol-soluble extract， while samples from Jiangxi have a high content of crocin Ⅰ.

Objective: To investigate whether membrane vesicles (MVs) of Streptococcus mutans （S.mutans） contain autoinducer-2 (AI-2) and to preliminarily explore the effects of these MVs on the growth and biofilm formation of S. mutans. Methods: MVs were isolated from the S. mutans UA159 strain using differential centrifugation. The isolated MVs were characterized by nanoparticle tracking analysis for particle size and concentration and observed by transmission electron microscopy. The presence of AI-2 was identified using the Vibrio harveyi BB170 bioluminescence assay: the BB170 diluent was supplemented with AB medium (control group), MV extract (MVs group), pre-ultrafiltration supernatant (Sup group), or post-ultrafiltration supernatant (Sup-af group). The effects of MVs on growth and biofilm formation were assessed using the S.mutans UA159 strain or a luxS deletion mutant as the control group, compared with experimental groups stimulated with gradient concentrations of MVs (MVs-2.0E+7, MVs-2.0E+8, and MVs-2.0E+9 groups). Growth curves, MTT assay, and colony-forming unit (CFU) counts were used to determine changes in growth capacity. Biofilm formation was evaluated using crystal violet staining, confocal laser scanning microscopy, and the anthrone method for polysaccharide quantification. Results: Enriched S. mutans MVs were successfully obtained, with an average particle size of approximately 94.19 nm and a concentration of 1.87E+11 particles/mL. The bioluminescence assay showed that the luminescence intensity of the Sup group was higher than that of the Sup-af group, and the MVs group exhibited higher intensity than the control group. Assessments via growth curves, MTT assay, and CFU counts indicated no significant differences in the growth capacity of the various S. mutans strains after treatment with different concentrations of MVs. Crystal violet staining quantification and confocal laser scanning microscopy observations revealed that high-concentration MV treatment (2.0E+9 particles/mL group) resulted in lower biofilm mass compared to the control. The anthrone method showed that the production of both water-soluble and water-insoluble polysaccharides was significantly lower in the high-concentration MV group than in the control. Conclusion S. mutans MVs contain the quorum sensing signal molecule AI-2. These MVs do not significantly affect the growth of S. mutans, but they can regulate biofilm formation and exhibit an inhibitory effect at high concentrations.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

BackgroundLow medication compliance among patients with severe mental disorders increases the disease burden on both the patients' families and the society. Medication adherence is influenced by numerous factors. Traditional methods such as Logistic regression struggle to quantify the importance of these factors. By introducing Extreme Gradient Boosting （XGBoost） combined with Shapley Additive Explanations （SHAP）， enables the quantification of the relative contribution weights of each factor， providing support for identifying the core influencing factors. ObjectiveTo explore the influencing factors of medication adherence among patients with severe mental disorders in Zhuhai， aiming to provide references for optimizing patient management strategies. MethodsExtract the data of patients with severe mental disorders who were registered on the mental health system platform in Zhuhai City from January 1， 2023 to March 31， 2025. A total of 9 329 patients were finally included for analysis. Influencing factors were screened using univariate analysis and multivariate logistic regression analysis， and an XGBoost model combined with the SHAP algorithm was constructed to quantify the importance of each influencing factor. ResultsAmong 9 329 patients， 8 446 demonstrated medication adherence， yielding an adherence rate of 90.53%. Multivariable analysis identified several risk factors significantly associated with medication non-adherence， being unmarried （OR=1.237， 95% CI： 1.019–1.502） or divorced （OR=1.389， 95% CI： 1.038–1.832）， a diagnosis of mental retardation with psychiatric disorders （OR=3.025， 95% CI： 2.402–3.796） or paranoid psychosis （OR=5.117， 95% CI： 3.086–8.299）， a disease duration of 2–4 years （OR=1.355， 95% CI： 1.085–1.696）， 4–6 years （OR=2.143， 95% CI： 1.671–2.747）， or >6 years （OR=1.681， 95% CI： 1.365–2.079）， lack of guardian subsidies （OR=1.412， 95% CI： 1.099–1.801）， absence of a disability certificate （OR=1.900， 95% CI： 1.588–2.282）， not being enrolled in care and support groups （OR=1.384， 95% CI： 1.183–1.617） or community services （OR=1.313， 95% CI： 1.042–1.645）， and not cohabiting with a guardian （OR=1.257， 95% CI： 1.048–1.501）. Conversely， the enrollment in special outpatient disease programs （OR=0.716， 95% CI： 0.609–0.842） and a family history of mental illness （OR=0.713， 95% CI： 0.503–0.982） were identified as protective factors. The XGBoost model exhibited robust predictive performance， with a sensitivity of 0.433， specificity of 0.944， accuracy of 0.891， Area Under the Curve （AUC） of 0.837， and F1 value of 0.449. Feature importance ranking indicated that the top three factors were disease duration， diagnosis， and the acquisition of disability certificates. ConclusionPolicy-based support （acquisition of disability certificates， special outpatient disease enrollment） and clinical disease characteristics （disease duration， diagnosis type） are key factors affecting medication adherence among patients with severe mental disorders in Zhuhai City. ［Funded by Zhuhai Medical Research Project （number， 2220009000281）］

BackgroundIndividuals with schizophrenia are prone to higher rates of hospital readmission， presenting significant clinical challenges and imposing considerable social burdens within the mental health domain. In recent years， various risk prediction models have been developed to forecast readmission in patients with schizophrenia and support clinical decision-making， but their predictive performance and clinical applicability require comprehensive evaluation. ObjectiveTo systematically evaluate the risk prediction models for readmission in patients with schizophrenia， so as to provide insights for the development of high-performance and highly applicable readmission risk prediction models for patients with schizophrenia. MethodsOn July 5， 2025， a systematic literature search was conducted across multiple electronic databases， including PubMed， Embase， Cochrane Library， Web of Science， CINAHL， CNKI， China Biomedical Literature Database， Wanfang Database， and VIP Database， to identify risk prediction models for readmission in patients with schizophrenia. The search period was from the establishment of the databases to July 1， 2025. Two researchers independently performed literature screening， data extraction， risk of bias assessment， and applicability assessment. ResultsA total of 9 studies were included in this review， encompassing 18 risk prediction models for readmission in patients with schizophrenia. Among them， 4 models reported the area under the receiver operating characteristic （ROC） curve （AUC）， ranging from 0.734 to 0.820， 16 models provided AUC values of 0.642–0.879 for internal validation， and 1 model demonstrated an AUC of 0.841 for external validation. Key predictors included disease duration and the concomitant therapy of antipsychotic medications. The risk of bias was assessed as "high" in all included studies. ConclusionThe development of risk prediction models for readmission in patients with schizophrenia remains in an exploratory stage. Although the model exhibits favorable predictive performance， it is associated with a high risk of bias and insufficient performance evaluation.

ObjectiveTo investigate the effect of Tougu Xiaotong capsules （TGXTC） on the regulation of chondrocyte PANoptosis， delay of chondrocyte degeneration， and improvement of the symptoms in knee osteoarthritis （KOA）. MethodsIn vivo experiments： 50 male C57BL/6 mice were randomly assigned into five groups （n=10 per group）： sham operation group， model group， low-dose TGXTC group （7.2 g·kg^-1）， high-dose TGXTC group （14.4 g·kg^-1）， and diclofenac sodium group （0.05 g·kg^-1）. Except for the sham group， KOA models were established in all other groups using the modified Hulth method. Following successful model induction， the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg^-1 for 6 weeks， while the diclofenac sodium group received 0.05 g·kg^-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score； micro-computed tomography （micro-CT） was used to scan the knee， hematoxylin-eosin （HE） staining and safranin O-fast green staining were used to observe the morphology of cartilage， transmission electron microscopy （TEM） was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence （IF） co-localization assays was performed to detect the co-localization of cleaved Caspase-3， receptor-interacting protein 3 （RlPK3）， and the N-terminal domain of gasdermin D （GSDMD-N） in cartilage tissue， while western blot was employed to detect the expression levels of cleaved Caspase-3， RIPK3， and GSDMD-N. In vitro experiments： The knee cartilages of 4-week-old SD rats were isolated， and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups： the control group， the model group （pretreated with 10 mg·L^-1 lipopolysaccharide （LPS） for 24 h followed by treatment with 1 μmol·L^-1 nigericin for 4 h）， and the TGXTC treatment group （pretreated with 10 mg·L^-1 LPS for 24 h， followed by exposure to 1 μmol·L^-1 nigericin for 4 h and subsequently treated with 100 mg·L^-1 TGXTC for an additional 24 h）. The levels of reactive oxygen species （ROS）， apoptosis， necroptosis， and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection， AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels （IL-1β and IL-18） were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis， including cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3. ResultsCompared with the sham group， the Lequesne MG scores were significantly up-regulated（P<0.01） in the model group， and the pathological changes of cartilage were significantly， with joint spaces narrower， osteophyte formation increased， secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis， necroptosis， and pyroptosis， along with markedly elevated expression of cleaved Caspase-3， RlPK3， and GSDMD-N in cartilage tissue （P<0.01）. In addition， The mean fluorescence intensities of ROS， orange-red fluorescence in AO/EB staining， green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group （P<0.01） . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased （P<0.01）. The expression of PANoptosis related proteins （cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3） were also significantly upregulated（P<0.05）. Compared to the model group， the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score， an increase in joint space， a decrease in osteophyte formation， diminished cartilage damage， reduced release of ROS， and alleviation of apoptotic， necroptotic， and pyroptotic processes in chondrocytes. Additionally， mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased （P<0.05）. Furthermore， the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions （P<0.05）. Similar results were observed in chondrocytes： cleaved Caspase-3， cleaved Caspase-8， RIPK3， ZBP1， GSDMD-N， and NLRP3 exhibited significant decreases as well （P<0.05）. ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.

Objective: To evaluate the effect of bioactive peptides combined with probiotics on serum uric acid (SUA) in patients with hyperuricemia (HUA), so as to provide the evidence for prevention and treatment of HUA. Methods: The patients with HUA aged 18 to 65 years were selected and randomly divided into an intervention group and a control group. The patients in the intervention group received bioactive peptides combined with probiotics for 28 days at a dose of 3 g/d, while the patients in the control group received an equal dose of placebos. Demographic information, body mass index (BMI), blood pressure and blood lipid were collected through questionnaire surveys, physical examination and laboratory tests. SUA levels were detected before and after 14 days and 28 days of interventions. The differences of SUA levels between the two groups were compared using generalized estimation equation. Results: Totally 108 patients with HUA were recruited, including 54 patients in the intervention group and 53 patients in the control group (1 dropout). Before interventions, there were no statistically significant differences in gender, age, course of HUA, exercise duration, frequency of alcohol consumption, frequency of meat broth consumption, BMI, prevalence of hypertension and prevalence of dyslipidemia between the two groups (all P>0.05). After 14 days of interventions, the SUA levels of the patients in the intervention group decreased by 3.00 μmol/L, while those in the control group increased by 7.00 μmol/L. After 28 days of interventions, the SUA levels of the patients in the intervention group and the control group decreased by 26.00 μmol/L and 16.00 μmol/L, respectively. However, there was no statistically significant interaction between the intervention time and group (both P>0.05). Subgroup analysis showed that after 28 days of interventions, the decrease in SUA levels in the patients aged 55 years and older and without hypertension in the intervention group was greater than those in the control group (both P<0.05). Conclusions Bioactive peptides combined with probiotics showed no significant difference in reducing SUA levels in patients with HUA compared to the control group. The effect was more significant for patients aged 55 years and older and without hypertension.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.