ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective:To explore the correlation between weekend moderate-to-vigorous physical activity(MVPA), weekday sedentary behavior(SB)and the risk of frailty in the elderly population monitored by wearable devices, and to provide a scientific basis for lifestyle interventions for frailty in the elderly.Methods:This study was based on the data of the UK Biobank from 2013 to 2015.A cross-sectional study design was adopted, and 33, 212 elderly people aged 60 and above with complete physical activity monitoring data were selected.The Frailty Index(FI)constructed by the deficit accumulation method was used to assess the frailty status.The correlation between the combined effect of weekday SB and weekend MVPA and the frailty status was analyzed, and the differences between genders were explored.Results:There were significant differences in physical activity indicators among the elderly with different frailty statuses.As the degree of frailty increased, the MVPA-related indicators showed a downward trend, while the weekday SB time gradually increased.There were sex differences in physical activity patterns and frailties.Compared with women, men had longer SB time on weekdays, lower metabolic equivalent of weekly MVPA consumption, and higher MVPA time on weekends, but the frailties index of women was slightly higher than that of men.After adjusting for confounding factors, the frailty risks for men and women in the subgroup with the lowest weekday SB and the highest weekend MVPA duration decreased by 46.9% and 59.8%, respectively( P<0.001)when compared to the highest-risk group. Conclusions:Based on the monitoring data from wearable devices, elderly individuals who reduced their SB time during weekdays and increased their MVPA time on weekends were associated with a lower risk of frailty, especially among women; which providing a new perspective for lifestyle-based intervention strategies for frailty among the elderly.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Objective:To explore the correlation between weekend moderate-to-vigorous physical activity(MVPA), weekday sedentary behavior(SB)and the risk of frailty in the elderly population monitored by wearable devices, and to provide a scientific basis for lifestyle interventions for frailty in the elderly.Methods:This study was based on the data of the UK Biobank from 2013 to 2015.A cross-sectional study design was adopted, and 33, 212 elderly people aged 60 and above with complete physical activity monitoring data were selected.The Frailty Index(FI)constructed by the deficit accumulation method was used to assess the frailty status.The correlation between the combined effect of weekday SB and weekend MVPA and the frailty status was analyzed, and the differences between genders were explored.Results:There were significant differences in physical activity indicators among the elderly with different frailty statuses.As the degree of frailty increased, the MVPA-related indicators showed a downward trend, while the weekday SB time gradually increased.There were sex differences in physical activity patterns and frailties.Compared with women, men had longer SB time on weekdays, lower metabolic equivalent of weekly MVPA consumption, and higher MVPA time on weekends, but the frailties index of women was slightly higher than that of men.After adjusting for confounding factors, the frailty risks for men and women in the subgroup with the lowest weekday SB and the highest weekend MVPA duration decreased by 46.9% and 59.8%, respectively( P<0.001)when compared to the highest-risk group. Conclusions:Based on the monitoring data from wearable devices, elderly individuals who reduced their SB time during weekdays and increased their MVPA time on weekends were associated with a lower risk of frailty, especially among women; which providing a new perspective for lifestyle-based intervention strategies for frailty among the elderly.

Objective:To construct and validate a prognostic model of colon cancer based on differentially expressed anoikis-related genes, and to preliminarily investigate the relationship between anoikis-related genes and the tumor immune microenvironment of colon cancer.Methods:A total of 472 cancer tissues samples of patients with colon cancer, RNA sequencing data and clinical data of 41 normal tissues samples were downloaded from the Cancer Genome Atlas (TCGA) database between the establishment time and July in 2024. A total of 919 genes related to anoikis were screened out from GeneCards database, and the common genes were selected from the RNA sequencing gene datasets of colon cancer and normal colon tissues in the TCGA database, among which the differentially expressed anoikis-related genes of colon cancer and normal colon tissues were screened out based on P < 0.05. Furthermore, genes related to the prognosis of 446 colon cancer patients with prognostic data in the TCGA database were screened by using univariate Cox proportional risk model; the genes with P < 0.05 were further screened out and a colon cancer prognosis model was constructed by using LASSO-Cox proportional risk model. The risk score of the above 446 colon cancer patients in the TCGA database was calculated according to the prognostic model, and the patients were divided into high-risk (≥ median value) group and low-risk (< median value) group according to the median risk score, and the overall survival of the 2 groups was analyzed by using the Kaplan-Meier method. The risk score based on R software-based time ROC program package was used to predict 1-year, 2-year, 3-year overall survival therapeutic efficacy of colon cancer patients in the TCGA database. According to the median risk score of colon cancer patients in the TCGA database, the patients in the International Cancer Genome Consortium (ICGC) database were divided into high-risk group and low-risk group. Kaplan-Meier method and receiver operating characteristic (ROC) curve were used to verify the predictive effect of the prognostic model. The differentially expressed genes between low-risk group and high-risk group stratified by prognostic model risk score in the TCGA database were used to perform single sample gene set enrichment analysis (ssGESA) of immune cells and immune function by using R software related programs. The differences in risk scores of patients with different immunophenotypes (including inflammator response type, wound healing type, interferon gamma dominant type and lymphocyte depletion type) were compared; and correlation analysis of infiltration and risk scores between immune cells and stromal cells in tumor microenvironment was made. Based on the tumor immune function and rejection (TIDE) database, the relationship between the prognostic model risk score and programmed death receptor ligand 1 (PD-L1) gene expression level was analyzed. Results:Based on anoikis-related genes in the GeneCards database, 236 differentially expressed anoikis-related genes between colon cancer tissues and normal tissues were obtained from the TCGA database. LASSO Cox regression was applied to establish a prognostic model constructed by 7 differentially expressed anoikis-related genes in cancer tissues and normal colon tissues related to the prognosis of colon cancer. Risk score = 0.366×TIMP1-0.404×NAT1+0.207×LTB4R2+0.075×INHBB+0.140×CD36-0.109×MMP3+2.994×OFCC1. The median risk score of 446 colon cancer patients in the TCGA database was 1.754 719 545. Survival analysis showed that the overall survival of colon cancer patients in high-risk group of the TCGA database was worse than that in low-risk group ( P < 0.001); ROC curve analysis showed that the area under the curve for predicting 1-year, 2-year and 3-year overall survival of patients in the TCGA database based on the prognostic model risk score was 0.705, 0.731 and 0.723, respectively. Kaplan-Meier method analysis showed that in the ICGC database, the overall survival of colon cancer patients in high-risk group was worse than that in low-risk group ( P = 0.041); ROC curve analysis showed that the area under the curve of prognostic model risk score for predicting 1-year and 2-year overall survival of colon cancer patients in the ICGC database was 0.663 and 0.966, respectively. ssGESA analysis showed that macrophage level in high-risk group was higher than that in low-risk group, helper T (Th) 1 cell and Th2 cell levels in high-risk group were lower than those in low-risk group (all P < 0.01). In terms of immune function, the cell killing activity and histocompatibility complex Ⅰ level in high-risk group were lower than those in low-risk group, and type Ⅱ interferon response score in high-risk group was higher than that in low-risk group (all P < 0.05). The analysis of immunophenotype showed that the risk score of inflammatory response type was higher than that of wound healing type ( P < 0.05), and there was no statistically significant difference in risk score between the other 2 types (all P > 0.05). Risk score was positively correlated with stromal cell infiltration score ( R = 0.340, P < 0.001) and immune cell infiltration score ( R = 0.148, P < 0.05); the expression level of PD-L1 in high-risk group was higher than that in low-risk group in the TCGA database ( P = 0.048), and the expression level of PD-L1 was positively correlated with risk score ( R = 0.130, P = 0.009). Conclusions:A prognostic model of colon cancer constructed by anoikis-related genes can better predict the prognosis of colon cancer patients, and anoikis-related genes may play an important role in tumor immunity of colon cancer.

Objective:To construct and validate a prognostic model of colon cancer based on differentially expressed anoikis-related genes, and to preliminarily investigate the relationship between anoikis-related genes and the tumor immune microenvironment of colon cancer.Methods:A total of 472 cancer tissues samples of patients with colon cancer, RNA sequencing data and clinical data of 41 normal tissues samples were downloaded from the Cancer Genome Atlas (TCGA) database between the establishment time and July in 2024. A total of 919 genes related to anoikis were screened out from GeneCards database, and the common genes were selected from the RNA sequencing gene datasets of colon cancer and normal colon tissues in the TCGA database, among which the differentially expressed anoikis-related genes of colon cancer and normal colon tissues were screened out based on P < 0.05. Furthermore, genes related to the prognosis of 446 colon cancer patients with prognostic data in the TCGA database were screened by using univariate Cox proportional risk model; the genes with P < 0.05 were further screened out and a colon cancer prognosis model was constructed by using LASSO-Cox proportional risk model. The risk score of the above 446 colon cancer patients in the TCGA database was calculated according to the prognostic model, and the patients were divided into high-risk (≥ median value) group and low-risk (< median value) group according to the median risk score, and the overall survival of the 2 groups was analyzed by using the Kaplan-Meier method. The risk score based on R software-based time ROC program package was used to predict 1-year, 2-year, 3-year overall survival therapeutic efficacy of colon cancer patients in the TCGA database. According to the median risk score of colon cancer patients in the TCGA database, the patients in the International Cancer Genome Consortium (ICGC) database were divided into high-risk group and low-risk group. Kaplan-Meier method and receiver operating characteristic (ROC) curve were used to verify the predictive effect of the prognostic model. The differentially expressed genes between low-risk group and high-risk group stratified by prognostic model risk score in the TCGA database were used to perform single sample gene set enrichment analysis (ssGESA) of immune cells and immune function by using R software related programs. The differences in risk scores of patients with different immunophenotypes (including inflammator response type, wound healing type, interferon gamma dominant type and lymphocyte depletion type) were compared; and correlation analysis of infiltration and risk scores between immune cells and stromal cells in tumor microenvironment was made. Based on the tumor immune function and rejection (TIDE) database, the relationship between the prognostic model risk score and programmed death receptor ligand 1 (PD-L1) gene expression level was analyzed. Results:Based on anoikis-related genes in the GeneCards database, 236 differentially expressed anoikis-related genes between colon cancer tissues and normal tissues were obtained from the TCGA database. LASSO Cox regression was applied to establish a prognostic model constructed by 7 differentially expressed anoikis-related genes in cancer tissues and normal colon tissues related to the prognosis of colon cancer. Risk score = 0.366×TIMP1-0.404×NAT1+0.207×LTB4R2+0.075×INHBB+0.140×CD36-0.109×MMP3+2.994×OFCC1. The median risk score of 446 colon cancer patients in the TCGA database was 1.754 719 545. Survival analysis showed that the overall survival of colon cancer patients in high-risk group of the TCGA database was worse than that in low-risk group ( P < 0.001); ROC curve analysis showed that the area under the curve for predicting 1-year, 2-year and 3-year overall survival of patients in the TCGA database based on the prognostic model risk score was 0.705, 0.731 and 0.723, respectively. Kaplan-Meier method analysis showed that in the ICGC database, the overall survival of colon cancer patients in high-risk group was worse than that in low-risk group ( P = 0.041); ROC curve analysis showed that the area under the curve of prognostic model risk score for predicting 1-year and 2-year overall survival of colon cancer patients in the ICGC database was 0.663 and 0.966, respectively. ssGESA analysis showed that macrophage level in high-risk group was higher than that in low-risk group, helper T (Th) 1 cell and Th2 cell levels in high-risk group were lower than those in low-risk group (all P < 0.01). In terms of immune function, the cell killing activity and histocompatibility complex Ⅰ level in high-risk group were lower than those in low-risk group, and type Ⅱ interferon response score in high-risk group was higher than that in low-risk group (all P < 0.05). The analysis of immunophenotype showed that the risk score of inflammatory response type was higher than that of wound healing type ( P < 0.05), and there was no statistically significant difference in risk score between the other 2 types (all P > 0.05). Risk score was positively correlated with stromal cell infiltration score ( R = 0.340, P < 0.001) and immune cell infiltration score ( R = 0.148, P < 0.05); the expression level of PD-L1 in high-risk group was higher than that in low-risk group in the TCGA database ( P = 0.048), and the expression level of PD-L1 was positively correlated with risk score ( R = 0.130, P = 0.009). Conclusions:A prognostic model of colon cancer constructed by anoikis-related genes can better predict the prognosis of colon cancer patients, and anoikis-related genes may play an important role in tumor immunity of colon cancer.

Objective To explore the pharmacological effects and regulatory mechanisms of Carthami Flos water extract and its main constituent,hydroxysafflower yellow A(HSYA),on primary dysmenorrhea rats with cold coagulation and blood stasis.Methods Forty-two female specific pathogen-free grade rats aged 6-8 weeks were divided into blank,model,HSYA(0.01 g/kg),ibuprofen(0.04 g/kg),and low(0.06 g/kg),medium(0.20 g/kg),and high(0.40 g/kg)Carthami Flos water extract dose groups using the random number table method,with six rats per group.A rat model was established using ice water bath stimulation combined with estradiol benzoate and oxytocin.Continuous gavage was administered for 6 days from the seventh day of modeling.After the intervention,the writhing reaction test was conducted.The rats,uteri,and ovaries were weighed to calculate the organ index.An enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the prostaglandin E2(PGE2)and prostaglandin F2α(PGF2α)contents in the uterus,thromboxane B2(TXB2)and 6-keto-prostaglondin F1α(6-keto-PGF1α)in plasma,and estradiol(E2)in the serum.Hematoxylin and eosin staining were used to detect the pathological changes in uterine tissue.Immunohistochemistry was used to determine cyclooxygenase-2(COX-2)expression in uterine tissue,whereas immunofluorescence was used to measure follicle-stimulating hormone receptor(FSH-R)expression in ovarian tissue.Western blotting was used to detect gonadotropin-releasing hormone receptor(GnRH-R)and FSH-R expression in uterine tissue.Results Compared with the blank group,the rats in the model group exhibited an increase in uterine and ovarian indices and increased PGE2 and PGF2α in the uterus.TXB2 in the plasma and E2 in the serum were also evaluated.Additionally,6-keto-PGF1α decreased,and COX-2,GnRH-R,and FSH-R expression in the uterus and FSH-R expression in the ovaries also increased(P＜0.05).The morphology of the uterine tissue was disordered.Compared with the model group,the low Carthami Flos water extract dose group showed a decrease in uterine index(P＜0.05).In the medium and high Carthami Flos water extract dose groups,the writhing response decreased,as did the uterine and ovarian indicesand PGE2 and TXB2 contents.The 6-keto-PGF1α content increased,whereas the GnRH-R protein expression in the uterus decreased(P＜0.05).The high Carthami Flos water extract dose group also showed a decrease in PGF2α and FSH-R protein expression in the uterus(P＜0.05).In the HSYA group,the writhing response decreased,the uterine and ovarian indices decreased,the PGE2,PGF2α,and TXB2 contents decreased,and GnRH-R and FSH-R protein expression decreased in the uterus(P＜0.05).The serum E2 levels of the groups that received Carthami Flos water extract at various doses and those of the HSYA group were reduced,and the uterine morphology was improved.COX-2 expression in the uterus and FSH-R protein expression in the ovaries were also reduced(P＜0.05).Conclusion Carthami Flos water extract and HSYA can improve the pathological state of primary dysmenorrhea rats with cold coagulation and blood stasis.Its mechanism may be related to regulating the hypothalamic-pituitary-ovary axis.

Objective To explore the pharmacological effects and regulatory mechanisms of Carthami Flos water extract and its main constituent,hydroxysafflower yellow A(HSYA),on primary dysmenorrhea rats with cold coagulation and blood stasis.Methods Forty-two female specific pathogen-free grade rats aged 6-8 weeks were divided into blank,model,HSYA(0.01 g/kg),ibuprofen(0.04 g/kg),and low(0.06 g/kg),medium(0.20 g/kg),and high(0.40 g/kg)Carthami Flos water extract dose groups using the random number table method,with six rats per group.A rat model was established using ice water bath stimulation combined with estradiol benzoate and oxytocin.Continuous gavage was administered for 6 days from the seventh day of modeling.After the intervention,the writhing reaction test was conducted.The rats,uteri,and ovaries were weighed to calculate the organ index.An enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the prostaglandin E2(PGE2)and prostaglandin F2α(PGF2α)contents in the uterus,thromboxane B2(TXB2)and 6-keto-prostaglondin F1α(6-keto-PGF1α)in plasma,and estradiol(E2)in the serum.Hematoxylin and eosin staining were used to detect the pathological changes in uterine tissue.Immunohistochemistry was used to determine cyclooxygenase-2(COX-2)expression in uterine tissue,whereas immunofluorescence was used to measure follicle-stimulating hormone receptor(FSH-R)expression in ovarian tissue.Western blotting was used to detect gonadotropin-releasing hormone receptor(GnRH-R)and FSH-R expression in uterine tissue.Results Compared with the blank group,the rats in the model group exhibited an increase in uterine and ovarian indices and increased PGE2 and PGF2α in the uterus.TXB2 in the plasma and E2 in the serum were also evaluated.Additionally,6-keto-PGF1α decreased,and COX-2,GnRH-R,and FSH-R expression in the uterus and FSH-R expression in the ovaries also increased(P＜0.05).The morphology of the uterine tissue was disordered.Compared with the model group,the low Carthami Flos water extract dose group showed a decrease in uterine index(P＜0.05).In the medium and high Carthami Flos water extract dose groups,the writhing response decreased,as did the uterine and ovarian indicesand PGE2 and TXB2 contents.The 6-keto-PGF1α content increased,whereas the GnRH-R protein expression in the uterus decreased(P＜0.05).The high Carthami Flos water extract dose group also showed a decrease in PGF2α and FSH-R protein expression in the uterus(P＜0.05).In the HSYA group,the writhing response decreased,the uterine and ovarian indices decreased,the PGE2,PGF2α,and TXB2 contents decreased,and GnRH-R and FSH-R protein expression decreased in the uterus(P＜0.05).The serum E2 levels of the groups that received Carthami Flos water extract at various doses and those of the HSYA group were reduced,and the uterine morphology was improved.COX-2 expression in the uterus and FSH-R protein expression in the ovaries were also reduced(P＜0.05).Conclusion Carthami Flos water extract and HSYA can improve the pathological state of primary dysmenorrhea rats with cold coagulation and blood stasis.Its mechanism may be related to regulating the hypothalamic-pituitary-ovary axis.