Objective To evaluate the value of serum Mac-2 binding protein (M2BP) for assessment of the severity of schisto somiasis-induced liver fibrosis, so as to provide insights into non-invasive diagnosis and disease surveillance of liver fibrosis caused by schistosomiasis. Methods A total of 234 individuals with a history of Schistosoma japonicum infection were sampled from Xinhua Village, Lushan City, Jiangxi Province from 2019 to 2020, and 234 serum samples were collected from all participants. All participants received B-ultrasound examinations of the liver. Serum samples were categorized into four groups (grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis groups) according to B-ultrasound examination results, and then, each group was randomly divided into a receiver operating characteristic (ROC) curve group and an efficacy assessment group at a ratio of 7∶3. Serum M2BP concentration was measured in four groups using the enzyme-linked immunosorbent assay (ELISA), and differences in serum M2BP concentrations were compared with analysis of variance and Spearman correlation analysis. Serum M2BP concentration was subjected to ROC curve analysis among individuals with different grades of schistosomiasis-induced liver fibrosis in the ROC curve group to determine the optimal diagnostic threshold of M2BP concentration at different fibrosis grades, and the area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance. The diagnostic accuracy was verified by comparing the accordance rate and Kappa consistency test in the efficacy assessment group. Results Among 234 serum samples, there were 79 samples with grade 0 schistosomiasis-induced liver fibrosis, 87 samples with Grade Ⅰ, 46 samples with Grade Ⅱ and 22 samples with Grade Ⅲ according to the B-ultrasound examinations. The mean serum M2BP concentrations were (0.40 ± 0.31) [95% confidence interval (CI): (0.33, 0.47)], (0.64 ± 0.48) [95% CI: (0.53, 0.74)], (1.76 ± 0.58) [95% CI: (1.59, 1.93)] μg/mL and (2.56 ± 0.93) [95% CI: (2.14, 2.97)] μg/mL in the four groups, respectively (F = 150.796, P < 0.001), and the severity of schistosomiasis-induced liver fibrosis significantly positively correlated with serum M2BP concentration (rs = 0.715, P < 0. 001). The sample sizes of grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis sera were randomly allocated as follows: 55 versus 24, 61 versus 26, 32 versus 14, and 15 versus 7 in the ROC curve and efficacy assessment groups, respectively, and the serum M2BP concentrations were (0.39 ± 0.29) μg/mL and (0.42 ± 0.36) μg/mL (F = 0.196, P > 0.05), (0.59 ± 0.47) μg/mL and (0.75 ± 0.51) μg/mL (F = 1.967, P > 0.05), (1.73 ± 0.59) μg/mL and (1.85 ± 0.57) μg/mL (F = 0.417, P > 0.05), and (2.46 ± 0.64) μg/mL and (2.76 ± 1.41) μg/mL (F = 0.491, P > 0.05), respectively. ROC curve analysis showed that the optimal diagnostic thresholds of serum M2BP concentration were 0.347 86 μg/mL (AUC = 0.635, P < 0.05), 1.188 83 μg/mL (AUC = 0.938, P < 0.000 1) and 2.021 21 μg/mL (AUC = 0.821, P < 0.000 1) for grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis. In addition, the accordance rates between the optimal diagnostic threshold of serum M2BP and B-ultrasound examinations for predicting grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induceed liver fibrosis were 69.23%, 85.71% and 71.43% (χ2 = 1.340, P > 0.05), and the overall Kappa consistency test showed moderate consistency [Kappa = 0.608, 95% CI: (0.428, 0.788); Z = 6.609, P < 0.000 1]. Conclusions Serum M2BP may serve as a potential biomarker for assessing moderate to advanced schistosomiasis-induced liver fibrosis; however, its diagnostic value for early-stage schistosomiasis-induced liver fibrosis remains limited.

OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

This paper outlines the development of artificial intelligence （AI） and its applications in traditional Chinese medicine （TCM） research， and elucidates the roles and advantages of large language models， knowledge graphs， and natural language processing in advancing syndrome identification， prescription generation， and mechanism exploration. Using spleen-stomach diseases as an example， it demonstrates the empowering effects of AI in classical literature mining， precise clinical syndrome differentiation， efficacy and safety prediction， and intelligent education， highlighting an upgraded research paradigm that evolves from data-driven and knowledge-driven approaches to intelligence-driven models. To address challenges related to privacy protection and regulatory compliance in cross-institutional data collaboration， a "trusted federated evidence-based analysis platform for TCM spleen-stomach diseases" is proposed， integrating blockchain-based smart contracts， federated learning， and secure multi-party computation. The deep integration of AI with privacy-preserving computing is reshaping research and clinical practice in TCM spleen-stomach diseases， providing feasible pathways and a technical framework for building a high-quality， trustworthy TCM big-data ecosystem and achieving precision syndrome differentiation.

[摘 要] 目的：探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）、尿苷二磷酸-葡萄糖醛酸脱羧酶1（UXS1）在肝细胞癌（HCC）中的表达特征、预后价值及两者协同作用的分子机制。方法：整合UALCAN、cBioPortal、ENCORI、TISCH2、GDSC等公共数据库的转录组数据，对IGF2BP3和UXS1进行表达、预后评估、功能富集及药物敏感性等分析。收集GEO数据库的单细胞RNA测序（scRNA-seq）数据，分析细胞通信、单细胞代谢评分，系统解析IGF2BP3-UXS1轴在HCC中的具体作用。结果：IGF2BP3、UXS1在HCC组织中均显著高表达，且高表达患者总生存期显著缩短（均P < 0.05）。采用CRISPP技术敲除IGF2BP3或UXS1后，多种HCC细胞的增殖能力受到明显抑制。scRNA-seq分析揭示了IGF2BP3、UXS1在肝细胞等细胞类型中的广泛表达分布，前者在细胞分化晚期上调，后者则在细胞分化早、中期高表达。IGF2BP3、UXS1高表达组均显著激活了MIF通路，同时IGF2BP3的高表达削弱了成纤维细胞的相互作用，而UXS1的高表达则增强了T细胞的信号转导功能。IGF2BP3与UXS1在表达相关性中存在显著的正相关（r = 0.432，P < 0.05）。沉默IGF2BP3结合位点会导致UXS1表达水平变化（F = 0.333）。功能富集分析提示，IGF2BP3与UXS1协同调控能量代谢、蛋白质翻译等生物学过程。在IGF2BP3或UXS1高表达的细胞亚群中，发现两者与多个糖代谢相关通路存在显著关联。IGF2BP3、UXS1高表达的患者对优普色替等药物表现出显著的敏感性，还对药物那维托克等表现出显著的耐药性。结论： IGF2BP3、UXS1在HCC中高表达，两者通过调控糖代谢重编程的协同作用促进HCC恶性生物学行为。

Objective: To explore the latent classes of peer victimization among junior high school students, and to analyze the association between the characteristics of different classes and non suicidal self injury(NSSI) behavior,so as to provide scientific basis for the prevention and intervention of NSSI behavior among junior high school students. Methods: A census method was used to select 19 738 students from 16 junior high schools in a central urban area of Wuhan as research subjects from November to December 2024. The Multidimensional Peer Victimization Scale and a self designed NSSI questionnaire were used to assess peer victimization and NSSI behaviors. Latent profile analysis (LPA) was used to identify latent classes of peer victimization among students by sex. Binary Logistic regression model was used to analyze the association between latent classes of peer victimization and NSSI behavior among junior high school students of different genders. Results: Latent patterns of peer victimization among boys were classified into 4 groups:no victimization group (85.8%, n =8 874), low victimization-verbal type group (6.6%, n =682), low victimization-mixed type group (5.7%, n =587) and high victimization group (1.9%, n =195); girls were classified into 4 groups:no victimization group (87.0%, n =8 179), low victimization group (7.5%, n =702), high victimization-social type group (3.8%, n =360) and high victimization-physical type group (1.7%, n =159). After controlling for only child status, place of residence, parenting style, and self rated family socioeconomic status, binary Logistic regression analysis showed that the risk of NSSI behavior among boys increased sequentially in the low victimization-verbal type group( OR =4.14, 95% CI =3.22-5.31), low victimization-mixed type group ( OR =4.75, 95% CI =3.68-6.13), and high victimization group ( OR =8.26, 95% CI =5.83-11.71) compared to the no victimization group; the risks of NSSI behavior among girls increased sequentially in the low victimization group ( OR =3.06, 95% CI = 2.51-3.72), high victimization-social type group ( OR =4.01, 95% CI =3.13-5.15), and high victimization-physical type group ( OR =6.18, 95% CI =4.38-8.73) compared to the no victimization group (all P <0.05). Conclusions There are gender differences in the latent classes of peer victimization among junior high school students and the risk of NSSI behavior varies across different victimization classes. Targeted prevention and intervention should be implemented based on the gender of junior high school students and the characteristics of peer victimization students experience.

Objective: To determine the association between exposure to entertainment screen content on mobile phones and symptoms of anxiety-depression co-morbidity among college students,so as to provide evidence for mental health interventions. Methods: A baseline survey was conducted from April to May 2019. A total of 1 135 college students were selected from one university each in Shangrao City, Jiangxi Province and Hefei City, Anhui Province using cluster random sampling method. A follow up study was conducted in November 2019, resulting in 1 110 matched valid responses. Self rating questionnaires were used to assess the exposure of entertainment screen content. The Depression Anxiety Stress Scale-21(DASS-21) and the Patient Health Questionnaire-9 (PHQ-9) were used to evaluate the anxiety symptoms, depressive symptoms, and symptoms of anxiety-depression co-morbidity among college students. A multivariate binary Logistic regression model was constructed following initial intergroup comparisons with Chi-square test to determine the association between baseline exposure to mobile entertainment screen content and the risk of symptoms of anxiety depression co-morbidity at baseline and the 6 month follow up. Results: The prevalence rates of symptoms of anxiety-depression co-morbidity among college students were 25.4% and 20.6% at baseline and follow up, respectively.After adjusting for confounding factors such as gender, self rated family economic status and self rated health status, the results of multivariate binary Logistic regression analysis showed that compared with the appropriate exposure level group, the exposure of entertainment screen content on mobile phones at baseline, including frequent exposure to reading( OR =1.65,95% CI =1.14-2.39), occasional exposure to other entertainment screen content ( OR =1.46,95% CI =1.01-2.10)and frequent exposure to other entertainment screen content( OR =1.76,95% CI =1.20-2.60), increased the co-occurrence risk of symptoms of anxiety-depression co-morbidity among college students during the follow up period (all P <0.05). Conclusion Occasional or frequert exposure to mobile entertainment screen content can increase the risk of symptoms of anxiety depression co-morbidity among college students.

This paper summarizes the experience of professor LIU Shangyi in differentiating and treating rectal carcinoma from the perspective of "treating ulcers as tumors". It is believed that the manifestations of rectal cancer， such as anal itching， cauliflower-like or ulcerative tumors， and bloody stools， are similar to external skin itching， skin ulceration， swelling， and skin bleeding. Therefore， the treatment principles of sores and ulcers department can be applied to treat tumors. Following the diagnostic and treatment approach of dermatology regarding the clinical typical symptoms， for anal itching， the main treatment is to dispel wind and remove dampness， clear heat to relieve itching， using "skin medicinals" such as Difuzi （Fructus Kochiae） and Baixianpi （Cortex Dictamni）， as well as wind medicinals such as Shengma （Rhizoma Cimicifugae） and Fangfeng （Radix Saposhnikoviae）. For constipation， the method of clearing heat and resolving toxins， unblocking the bowels and discharging heat can be used， commonly using Baitouweng （Radix Pulsatillae）， Donglingcao （Herba Rabdosiae Rubescentis） and Dahuang （Radix et Rhizoma Rhei）. In terms of mucosal ulcers， it is critical to differentiate between yin and yang； the treatment of yang ulcers should focus on clearing heat and resolving toxins， commonly using modified Xianfang Huoming Beverage （仙方活命饮）； for yin ulcers， emphasis should be placed on removing dampness and resolving phlegm， commonly with modified Yiyi Fuzi Baijiang Powder （薏苡附子败酱散）. For bloody stool， differentiation is made between deficiency and excess， with the use of Diyu （Radix Sanguisorbae） and Huaihua （Flos Sophorae） for excess syndrome to cool and stop blee-ding， and both herbs dry-fried until charred combined with liver-tonifying medicinals for deficiency syndrome

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.