Acute myeloid leukemia (AML) is characterized by marked biological heterogeneity, and molecular classification is essential for therapeutic decision-making and prognostic stratification. With the advancement of precision oncology, genotype-directed targeted therapy has emerged as a critical element in the management of AML. Although KMT2A rearrangements and NPM1 mutations arise from distinct molecular events, both converge on aberrant activation of the HOX/MEIS1 transcriptional program, thereby sustaining the self-renewal of leukemic stem/progenitor cells and impairing myeloid differentiation to promote leukemogenesis and disease progression. Menin, encoded by the tumor suppressor gene MEN1, functions as a nuclear scaffold protein and serves as an essential mediator for the assembly of KMT2A fusion-driven transcriptional complexes, recruitment of cooperative cofactors, and stabilization of oncogenic transcriptional networks. The disruption of the Menin-KMT2A interaction represents a mechanistically grounded therapeutic strategy. In recent years, multiple Menin inhibitors have progressed to clinical development and exhibited clinically significant activity in AML subsets with KMT2A rearrangements or NPM1 mutations. This review summarizes current progress in the research and clinical application of Menin inhibitors in AML, focusing on pharmacological mechanisms, efficacy and safety profiles derived from clinical studies, and emerging resistance mechanisms, including recurrent MEN1 hotspot mutations and epigenetic/transcriptional reprogramming. We further discuss rational combination approaches and directions for the development of next-generation agents, aiming to enhance clinical practice and guide future research.

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.

Chimeric antigen receptor (CAR) T-cell therapy for B-cell hematologic malignancies has achieved breakthrough success; however, its efficacy for acute myeloid leukemia (AML) is constrained by the lack of highly specific tumor antigens and the expression of shared targets on normal hematopoietic stem/progenitor cells, increasing the risk of on-target myelosuppression and cytokine release syndrome (CRS). By contrast, CAR-NK cell therapy, an emerging strategy that leverages the innate antitumor activity of natural killer cells, is associated with low rates of CRS and graft-versus-host disease. Early clinical studies also indicate its favorable safety profile with preliminary antileukemic activity. This review summarizes recent advances in CAR-NK therapy for AML and discusses future directions and potential avenues for clinical translation.

The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerular disease (C3G) and age-related macular degeneration (AMD). Complement factor B (CFB) is a trypsin-like serine protein that circulates in the human bloodstream in a latent form. As a key node of the alternative pathway, it is an important target for the treatment of diseases mediated by the complement system. With the successful launch of iptacopan, the CFB small molecule inhibitors has become a current research hotspot, a number of domestic and foreign pharmaceutical companies are actively developing CFB small molecule inhibitors. In this paper, the research progress of CFB small molecule inhibitors in recent years is systematically summarized, the representative compounds and their activities are introduced according to structural types and design ideas, so as to provide reference and ideas for the subsequent research on CFB small molecule inhibitors.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

Based on copper death, this study investigates the effect and mechanism of Shenmai Injection on isoproterenol(ISO)-induced myocardial fibrosis(MF) in rats. SPF-grade male SD rats were randomly divided into a normal group, model group, captopril(5 mg·kg~(-1)) positive control group, and Shenmai Injection low(6 mL·kg~(-1)), medium(9 mL·kg~(-1)), and high(12 mL·kg~(-1)) dose groups. Except for the normal group, the rats in the other groups were subcutaneously injected with ISO(5 mg·kg~(-1)) once a day for 10 consecutive days to establish an MF model. Starting from the second day after successful modeling, intraperitoneal injections of the respective treatments were administered for 28 consecutive days. Hematoxylin-eosin(HE) and Masson staining were used to observe pathological changes and fibrosis levels in the myocardial tissue. Colorimetry was employed to detect serum Cu~(2+) concentration in rats. The levels of inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), as well as mitochondrial energy metabolites adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in serum were measured using enzyme-linked immunosorbent assay(ELISA). Western blot was performed to detect the expression of collagen Ⅰ(Col-Ⅰ), collagen Ⅲ(Col-Ⅲ), and copper death-related proteins dihydrolipoamide acetyltransferase(DLAT), ferredoxin 1(FDX1), lipoic acid synthetase(LIAS), and heat shock protein 70(HSP70) in myocardial tissue. Immunofluorescence was used to detect the expression of DLAT, FDX1, and HSP70, while immunohistochemistry was conducted to examine the expressions of DLAT, FDX1, LIAS, and HSP70. The results showed that, compared to the model group, the myocardial structure disorder and collagen fiber deposition in the drug treatment groups were significantly improved, the cardiac index level was reduced, serum Cu~(2+), IL-6, IL-1β, IL-18, TNF-α, ADP, and AMP levels were significantly decreased, ATP levels were significantly increased, and the expressions of Col-Ⅰ, Col-Ⅲ, and HSP70 proteins in myocardial tissue were significantly reduced, while the expressions of DLAT, FDX1, and LIAS proteins were significantly elevated. In conclusion, Shenmai Injection effectively alleviates myocardial structure disorder and interstitial collagen fiber deposition in ISO-induced MF rats, promotes copper excretion, and reduces copper death in the ISO-induced rat MF model.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Myocardium/metabolism* ; Drug Combinations ; Fibrosis/metabolism* ; Copper/blood* ; Cardiomyopathies/genetics* ; Humans

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.