ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells （KGN） and ameliorates premature ovarian insufficiency （POI） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 （CCK-8） assay. Subsequently， the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined， KGN cells were categorized into the following groups： blank control （20% blank serum）， model （20% blank serum + 5 μmol·L^-1 cyclophosphamide）， Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide）， autophagy inhibitor （20% blank serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， autophagy inhibitor + Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， and estradiol valerate （20% estradiol valerate-containing serum + 5 μmol·L^-1 cyclophosphamide）. Following 48 hours of incubation， flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K， phosphorylated （p）-Akt， Akt， p-mTOR， and mTOR， along with the expression levels of autophagy-related proteins such as Beclin1， autophagy-related 5 homolog （ATG5）， and microtubule-associated protein 1 light chain 3 （LC3）， in each group. Additionally， monodansylcadaverine （MDC） staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L^-1 cyclophosphamide for 48 h successfully established a POI model， marked by a significant inhibition of KGN cell proliferation. Notably， the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation， with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group， the model group displayed an elevated apoptosis rate （P<0.01）， reduced protein levels of PI3K， p-Akt， and p-mTOR （P<0.01）， increased protein levels of Beclin1， LC3， and ATG5 （P<0.01）， no significant alterations in the protein levels of Akt and mTOR， and an enhanced MDC autophagy fluorescence intensity （P<0.01）. In comparison to that the model group， the apoptosis rates in the blank control group， model group， Zhuluan decoction-containing serum group， autophagy inhibitor group， autophagy inhibitor + Zhuluan decoction-containing serum group， and estradiol valerate group all reduced （P<0.05， P<0.01）， with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K， p-Akt， and p-mTOR were higher in other groups than in the model group （P<0.05， P<0.01）， being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group （P<0.01）. The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group （P<0.05， P<0.01）. The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group （P<0.05， P<0.01）， while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model， thus managing POI.

ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells （KGN） and ameliorates premature ovarian insufficiency （POI） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 （CCK-8） assay. Subsequently， the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined， KGN cells were categorized into the following groups： blank control （20% blank serum）， model （20% blank serum + 5 μmol·L^-1 cyclophosphamide）， Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide）， autophagy inhibitor （20% blank serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， autophagy inhibitor + Zhuluan decoction-containing serum （20% Zhuluan decoction-containing serum + 5 μmol·L^-1 cyclophosphamide + 20 μmol·L^-1 chloroquine phosphate）， and estradiol valerate （20% estradiol valerate-containing serum + 5 μmol·L^-1 cyclophosphamide）. Following 48 hours of incubation， flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K， phosphorylated （p）-Akt， Akt， p-mTOR， and mTOR， along with the expression levels of autophagy-related proteins such as Beclin1， autophagy-related 5 homolog （ATG5）， and microtubule-associated protein 1 light chain 3 （LC3）， in each group. Additionally， monodansylcadaverine （MDC） staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L^-1 cyclophosphamide for 48 h successfully established a POI model， marked by a significant inhibition of KGN cell proliferation. Notably， the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation， with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group， the model group displayed an elevated apoptosis rate （P<0.01）， reduced protein levels of PI3K， p-Akt， and p-mTOR （P<0.01）， increased protein levels of Beclin1， LC3， and ATG5 （P<0.01）， no significant alterations in the protein levels of Akt and mTOR， and an enhanced MDC autophagy fluorescence intensity （P<0.01）. In comparison to that the model group， the apoptosis rates in the blank control group， model group， Zhuluan decoction-containing serum group， autophagy inhibitor group， autophagy inhibitor + Zhuluan decoction-containing serum group， and estradiol valerate group all reduced （P<0.05， P<0.01）， with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K， p-Akt， and p-mTOR were higher in other groups than in the model group （P<0.05， P<0.01）， being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group （P<0.01）. The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group （P<0.05， P<0.01）. The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group （P<0.05， P<0.01）， while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model， thus managing POI.

Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Objective: To explore the relationship between non suicidal self injury (NSSI) behavior and serum lipid levels as well as thyroid function among college students with depression. Methods: A total of 169 college students with depression in the psychiatry departments of tertiary hospitals (grade 3A and 3B) in Ningbo from December 2023 to April 2025 were selected. The Adolescent Self injury Scale (ASIS) was used to assess the presence of NSSI, and participants were accordingly divided into a NSSI group ( n =51) and a non NSSI group ( n =118). General demographic data (including gender, age, and family situation) were collected from both groups. Blood tests were performed to measure lipid profiles [triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C)] and thyroid hormones [triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH)]. Multivariate Logistic regression was employed to analyze risk factors for NSSI, and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of serum lipid and thyroid hormone levels for NSSI occurrence in college students with depression. Results: The levels of TC, LDL-C, and TSH in the NSSI group were (4.02±0.73) mmol/L, (2.32±0.36) mmol/L, and (6.57±1.95) mU/L , which were significantly higher than those in the non NSSI group [(3.41±0.56) mmol/L, (2.00±0.27) mmol/L, and ( 4.48± 1.09) mU/L, respectively] ( t =5.32, 5.60, 7.20, all P <0.05). Logistic regression analysis revealed that college students from single parent/reconstituted families, those who had experienced school bullying, and those with higher levels of TC, LDL-C, and TSH had a significantly increased risk of engaging in NSSI ( OR =5.22, 6.12, 5.90, 83.64, 3.64, all P <0.05). ROC curve analysis demonstrated that the combined detection of TC, LDL-C, and TSH had high diagnostic efficacy for predicting NSSI in college students with depression, with a sensitivity of 86.3% and a specificity of 94.9%. Conclusions NSSI behavior in college students with depression is associated with serum lipid levels and thyroid function. These biomarkers may serve as useful reference indicators for assessing the conditions of these patients.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

ObjectiveThis paper aims to explore the in vitro anti-psoriasis activity and potential mechanism of Kangfuxin liquid （KFX liquid）， providing experimental evidence for the anti-psoriasis effect of KFX liquid. MethodsFirstly， the uninduced human immortalized keratinocyte cells （HaCaT cells） were divided into seven groups， namely the control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. After being treated with different concentrations of KFX liquid， the effect of KFX liquid on the normal cell proliferation was detected by using the cell counting kit-8 （CCK-8） method. Secondly， the uninduced HaCaT cells were divided into six groups， namely the control group and recombinant human interleukin-7A （rh-IL-7A） groups with different doses （5， 10， 50， 100， 120 g·L^-1）. After being treated with different concentrations of recombinant human interleukin-17A （rh IL-17A） liquid， the effect of rh IL-17A on cell proliferation was detected. The optimal induction concentration was screened. Then， normal HaCaT cells were divided into a control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. Except for the control group， the other groups established psoriasis cell models with the optimal induction concentration of rh IL-17A. After being treated with different concentrations of KFX liquid， the effects of KFX liquid on the psoriasis-like HaCaT cell proliferation were investigated. Finally， the uninduced HaCaT cells were divided into six groups， namely the control group， rh IL-17A group， methotrexate （MTX） group， and KFX liquid groups with different doses （20， 40， 80 g·L^-1）. Except for the control group， the other groups used the optimal induction concentration of rh IL-17A to establish psoriasis cell models. After being treated with different drugs， the cell migration levels were detected through scratch assays， and real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the relative mRNA expression levels of Ki-67 antigen （Ki67）， S100 calcium-binding protein A7 （S100A7）， S100 calcium-binding protein A8 （S100A8）， and S100 calcium-binding protein A9 （S100A9）， thereby comprehensively evaluating the in vitro anti-psoriasis activity of KFX liquid. By detecting the relative mRNA expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and chemokine-20 （CXCL-20） inflammatory-related factors in psoriasis-like HaCaT cells and the protein expression levels of Janus kinase 3 （JAK3）， phosphorylated Janus kinase 3 （p-JAK3）， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）， the mechanism was explored. ResultsCompared with that of control group， when treated with 80 g·L^-1 KFX liquid for 72 h （P<0.05） and at different times with 160 g·L^-1 KFX liquid， the HaCaT cell proliferation activity was significantly affected （P<0.01）， while the other concentrations of KFX liquid had no significant differences in cell morphology and cell proliferation activity at different times， indicating that the KFX liquid is relatively safe for HaCaT cells and has no obvious toxic side effects. Compared with that of control group， when treated with different concentrations of rh IL-17A for 24 h， the HaCaT cell proliferation activity was significantly enhanced， and the cell activity was the strongest when the concentration was 100 μg·L^-1 （P<0.05）， with a density close to 100% and intact cell morphology， indicating that 100 μg·L^-1 is the optimal concentration for inducing HaCaT cell proliferation. The results of the KFX liquid treatment on rh IL-17A-induced psoriasis-like cells show that the KFX liquid not only effectively inhibits the rh IL-17A-induced psoriasis-like HaCaT cell proliferation activity （P<0.01）， but also significantly reduces the migration ability of rh IL-17A-induced psoriasis-like HaCaT cells （P<0.01）， and the relative mRNA expression levels of Ki67， S100A7， S100A8， and S100A9 （P<0.01）. Moreover， the KFX liquid can significantly reduce the relative mRNA expression levels of IL-1β， IL-6， and CXCL-20 in rh IL-17A-induced psoriasis-like cells （P<0.01）， and significantly inhibit the phosphorylation levels of JAK3 and STAT3 proteins （P<0.05， P<0.01）. ConclusionThe KFX liquid has no obvious toxicity to uninduced HaCaT cells. It can inhibit rh IL-17A-induced psoriasis-like HaCaT cell proliferation， reduce the cell migration ability， and has good in vitro anti-psoriasis activity. Its action mechanism may be related to downregulating the expression levels of inflammation-related cytokines in the JAK3/STAT3 signaling pathway and inhibiting the phosphorylation levels of JAK3 and STAT3 proteins.

ObjectiveThis paper aims to explore the in vitro anti-psoriasis activity and potential mechanism of Kangfuxin liquid （KFX liquid）， providing experimental evidence for the anti-psoriasis effect of KFX liquid. MethodsFirstly， the uninduced human immortalized keratinocyte cells （HaCaT cells） were divided into seven groups， namely the control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. After being treated with different concentrations of KFX liquid， the effect of KFX liquid on the normal cell proliferation was detected by using the cell counting kit-8 （CCK-8） method. Secondly， the uninduced HaCaT cells were divided into six groups， namely the control group and recombinant human interleukin-7A （rh-IL-7A） groups with different doses （5， 10， 50， 100， 120 g·L^-1）. After being treated with different concentrations of recombinant human interleukin-17A （rh IL-17A） liquid， the effect of rh IL-17A on cell proliferation was detected. The optimal induction concentration was screened. Then， normal HaCaT cells were divided into a control group and KFX liquid groups with different doses （5， 10， 20， 40， 80， 160 g·L^-1）. Except for the control group， the other groups established psoriasis cell models with the optimal induction concentration of rh IL-17A. After being treated with different concentrations of KFX liquid， the effects of KFX liquid on the psoriasis-like HaCaT cell proliferation were investigated. Finally， the uninduced HaCaT cells were divided into six groups， namely the control group， rh IL-17A group， methotrexate （MTX） group， and KFX liquid groups with different doses （20， 40， 80 g·L^-1）. Except for the control group， the other groups used the optimal induction concentration of rh IL-17A to establish psoriasis cell models. After being treated with different drugs， the cell migration levels were detected through scratch assays， and real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the relative mRNA expression levels of Ki-67 antigen （Ki67）， S100 calcium-binding protein A7 （S100A7）， S100 calcium-binding protein A8 （S100A8）， and S100 calcium-binding protein A9 （S100A9）， thereby comprehensively evaluating the in vitro anti-psoriasis activity of KFX liquid. By detecting the relative mRNA expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and chemokine-20 （CXCL-20） inflammatory-related factors in psoriasis-like HaCaT cells and the protein expression levels of Janus kinase 3 （JAK3）， phosphorylated Janus kinase 3 （p-JAK3）， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）， the mechanism was explored. ResultsCompared with that of control group， when treated with 80 g·L^-1 KFX liquid for 72 h （P<0.05） and at different times with 160 g·L^-1 KFX liquid， the HaCaT cell proliferation activity was significantly affected （P<0.01）， while the other concentrations of KFX liquid had no significant differences in cell morphology and cell proliferation activity at different times， indicating that the KFX liquid is relatively safe for HaCaT cells and has no obvious toxic side effects. Compared with that of control group， when treated with different concentrations of rh IL-17A for 24 h， the HaCaT cell proliferation activity was significantly enhanced， and the cell activity was the strongest when the concentration was 100 μg·L^-1 （P<0.05）， with a density close to 100% and intact cell morphology， indicating that 100 μg·L^-1 is the optimal concentration for inducing HaCaT cell proliferation. The results of the KFX liquid treatment on rh IL-17A-induced psoriasis-like cells show that the KFX liquid not only effectively inhibits the rh IL-17A-induced psoriasis-like HaCaT cell proliferation activity （P<0.01）， but also significantly reduces the migration ability of rh IL-17A-induced psoriasis-like HaCaT cells （P<0.01）， and the relative mRNA expression levels of Ki67， S100A7， S100A8， and S100A9 （P<0.01）. Moreover， the KFX liquid can significantly reduce the relative mRNA expression levels of IL-1β， IL-6， and CXCL-20 in rh IL-17A-induced psoriasis-like cells （P<0.01）， and significantly inhibit the phosphorylation levels of JAK3 and STAT3 proteins （P<0.05， P<0.01）. ConclusionThe KFX liquid has no obvious toxicity to uninduced HaCaT cells. It can inhibit rh IL-17A-induced psoriasis-like HaCaT cell proliferation， reduce the cell migration ability， and has good in vitro anti-psoriasis activity. Its action mechanism may be related to downregulating the expression levels of inflammation-related cytokines in the JAK3/STAT3 signaling pathway and inhibiting the phosphorylation levels of JAK3 and STAT3 proteins.

p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.