1.Evaluation of the application effectiveness and optimization strategies of confidential unit exclusion in Zhengzhou
Dan LIU ; Hongwei MA ; Tao WEN ; Yonglei LYU ; Mengru JI ; Ge SONG ; Huanyu LIU ; Mengdi FAN
Chinese Journal of Blood Transfusion 2026;39(3):379-383
Objective: To evaluate the practical effectiveness of confidential unit exclusion (CUE) in ensuring blood safety in Zhengzhou, analyze its application characteristics and existing problems, and provide a basis for optimizing blood safety management strategies. Methods: A retrospective analysis was conducted on CUE data handled by Henan Red Cross Blood Center from January 2019 to December 2024. Parameters such as the number of cases, demographic characteristics, reasons for exclusion, and time of report were statistically analyzed and compared with those of non-CUE. Results: From 2019 to 2024, the CUE reporting rate in Zhengzhou was 0.002 6% (40/1 547 666). CUE donors were predominantly male (65.00%, 26/40), aged 18-34 years (47.50%, 19/40), had college degree orabove (50.00%, 20/40), and were employees of enterprises or public institutions (32.50%, 13/40). Among the 40 CUE blood units, only one was reactive for anti-TP, while all others were qualified. The main reasons for CUE were recent vaccination (32.50%, 13/40), medical conditions unsuitable for donation (27.50%, 11/40), and high-risk sexual behavior (17.50%, 7/40). A total of 70.00% of reports occurred within 24 hours after donation, during which none of the corresponding blood units had been released; all units reported after more than 7 days had already been issued for clinical use, with no adverse transfusion reactions reported upon follow-up. Conclusion: The confidential unit exclusion program has played an active role in establishing a supplementary information feedback channel for blood donors. The procedure can be optimized by strengthening interactive communication and confirmation before donation, improving the accuracy of donors' self-assessment, and expanding convenient and rapid information-based reporting channels.
2.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
3.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
4.Precise identification of a cryptic balanced translocation in a couple with recurrent spontaneous abortions using C-MoKa technique.
Rui FAN ; Yaru LIU ; Tingting JI ; Xiaojuan XU ; Xuening DING ; Xiaoling MA
Chinese Journal of Medical Genetics 2026;43(1):64-69
OBJECTIVE:
Chromosome conformation-based karyotype analysis (C-MoKa) technology was used to test a couple who had experienced multiple adverse pregnancies in order to provide them with genetic counseling and reproductive guidance.
METHODS:
A couple presented at the Reproductive Medicine Center of the First Hospital of Lanzhou University in 2023 was selected as the study subject. Through C-MoKa testing, copy number variation sequencing (CNV-seq), and preimplantation genetic testing for aneuploidy (PGT-A), it was found that the couple's repeatedly miscarried fetuses and abnormal embryos exhibited highly similar chromosomal structural abnormalities. Using C-MoKa, the potential genetic abnormalities in both partners were traced, and reproductive guidance was provided based on the result. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-09).
RESULTS:
CNV-seq analysis of the couple's miscarriage fetal chorionic villi showed del(18)(q21.2q23)(28.90 Mb) and dup(13)(q31.2q34)(26.26 Mb). Chromosomal karyotyping analysis of both partners showed no abnormality. From 2024 to 2025, the couple underwent three rounds of PGT-A assisted reproduction. The first embryo test showed del(13)(q31.2q34)(26.77 Mb) and dup(18)(q21.2q23)(29.08 Mb). The second embryo test showed dup(13)(q31.2q34)(26.26 Mb) and del(18)(q21.2q23)(28.90 Mb). And the third embryo test results showed complex chromosomal abnormalities. In 2025, after genetic counseling, the couple had opted C-MoKa test, which has detected no abnormality in the wife, but a balanced 46,XY,t(13;18)(q31.2;q21.2) translocation in the husband.
CONCLUSION
As a high-throughput sequencing method based on the three-dimensional conformation of chromatin, C-MoKa has the advantages of high resolution and high accuracy, and can accurately detect balanced translocations with similar banding patterns. It has therefore offered a powerful new tool for chromosomal analysis.
Female
;
Humans
;
Male
;
Pregnancy
;
Abortion, Habitual/genetics*
;
DNA Copy Number Variations
;
Karyotyping/methods*
;
Preimplantation Diagnosis
;
Translocation, Genetic
5.Study on the mechanism of CD151 YXXφ motif point mutant regulating vascular permeability through vesicle internalization and recycling
Shupeng JIANG ; Shilang FAN ; Luying JIANG ; Zixuan ZHANG ; Mengmeng JI ; Houjuan ZUO ; Jingbo LIU
Acta Universitatis Medicinalis Anhui 2026;61(6):1003-1012
ObjectiveTo investigate whether the CD151 YXXφ motif point mutant affects vascular permeability by regulating vesicle internalization and recycling. MethodsCD151 knockout (KO) and wild-type (WT) mice were used. A modified Miles assay was performed to compare vascular permeability in the dorsal and postauricular skin of the two groups of mice under vascular endothelial growth factor A (VEGF-A) stimulation. The CD151 YXXφ motif point mutant YALA was constructed and transfected into human endothelial cells (EA.hy926) using an adenoviral vector. Multiple experimental groups were set up to detect the permeability of endothelial cell monolayers to FITC-dextran under baseline conditions and after VEGF-A stimulation. Western blot (WB), RT-qPCR, and immunofluorescence were used to examine the expression and distribution of VE-cadherin. The internalization rate of VE-cadherin was quantitatively compared using a cell surface biotinylation assay. Phalloidin was used to label F-actin to observe changes in cytoskeletal tension. ResultsThe Miles assay showed that under VEGF-A stimulation, dye extravasation in the dorsal and postauricular skin of KO mice was significantly higher than that in WT mice (all P<0.05). At 60 min and 120 min after VEGF-A stimulation, the permeability of endothelial cell monolayers overexpressing the YALA mutant to FITC-dextran significantly increased (P<0.05). WB and RT-qPCR results indicated that the YALA mutant did not affect the total protein or mRNA expression levels of VE-cadherin. Immunofluorescence revealed that the YALA mutant disrupted the continuous distribution of VE-cadherin on the cell membrane and its perinuclear co-localization with CD151 under VEGF-A stimulation. The cell surface biotinylation assay confirmed that the YALA mutant significantly reduced the internalization rate of VE-cadherin (P<0.05). Cytoskeletal staining showed that the YALA mutant caused the formation of thick tension fibers in the actin cytoskeleton of endothelial cells, indicating cell contraction. ConclusionThe CD151 YXXφ motif point mutation affects vesicle internalization and recycling in endothelial cells, influences the expression and internalization of VE-cadherin, and consequently affects vascular permeability.
6.A clinical study on the recurrence factors and revision surgical outcomes of recurrent thyroglossal duct cysts and fistulas in children.
Haigang ZHANG ; Mingyue FAN ; Weicang JI ; Xinghe ZHAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(5):482-485
Objective:To explore the clinical manifestations, recurrence factors, and outcomes of revision surgery for recurrent thyroglossal duct cysts and fistulas in children. Methods:A retrospective study was conducted on the clinical manifestations, the relationship between cysts/ fistulas and residual hyoid bone of 10 patients with recurrent thyroglossal cysts and fistulas admitted to our hospital from July 2015 to July 2023, as well as the methods and effects of revision surgery. Results:The recurrence time after the initial surgery was between 7 months and 6 years, with an average of 2 years and 1 month.Clinical manifestations: 50%(5 cases) of patients have recurrent cysts near the incision, 40%(4 cases) had recurrent infections at the incision and eventually form fistulas, and 10%(1 case) experienced sleep snoring and pharyngeal trouble, were diagnosed with lingual thyroglossal duct cyst through laryngoscopy. All cysts or fistulas are connected to residual hyoid bodies, and three cases have intact hyoid bodies.Revision surgery: Nine cases underwent modified Sistrunk surgery, removing cysts, fistulas, and residual hyoid bodies. Suspension laryngoscopy and coblation were employed to treat the lingual thyroglossal duct cyst. After the revision surgery, follow-up was conducted for 8 months to 3 years, and no recurrence was found. Conclusion:All recurrences of thyroglossal duct cysts in this study were associated with residual hyoid bodies. Therefore, for thyroglossal duct cysts or fistulas, whether it is the first surgery or a revision surgery, it is recommended to choose the optimized Sistrunk operation, with the key point being complete resection of the hyoid body. Cases with lingual thyroglossal duct cyst can be treated with suspension laryngoscopy by coblation. Whether to remove the residual hyoid body requires further observation.
Humans
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Thyroglossal Cyst/surgery*
;
Retrospective Studies
;
Recurrence
;
Reoperation
;
Fistula/surgery*
;
Child
;
Hyoid Bone/surgery*
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Male
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Female
;
Treatment Outcome
;
Laryngoscopy
;
Child, Preschool
7.Clinical analysis of the low-temperature coblation resection of lingual thyroglossal duct cysts in children under self-retaining laryngoscope.
Weicang JI ; Haigang ZHANG ; Mingyue FAN ; Xinghe ZHAO ; Suna YANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(8):763-770
Objective:To explore the clinical efficacy of the coblation resection of lingual thyroglossal duct cysts under self-retaining laryngoscopy. Methods:A retrospective analysis was conducted on the clinical data of 22 patients with lingual thyroglossal duct cysts admitted to our hospital from December 2016 to December 2023. There were 16 males and 6 females, aged 2 years to 12 years and 3 months(mean: 4 years 1 month; median: 3 years 3 months). The lingual thyroglossal duct cysts were removed by coblation under self-retaining laryngoscopy. If the cysts could not be removed completely, the epithelial cells of the remaining cysts would be ablated. Results:There were 22 cases of lingual thyroglossal duct cysts,13 cases (59.1%) of lingual thyroglossal duct cysts had laryngeal stridor and dyspnea. The postoperative follow-up period is 3 months to 7 years. 11 cases (50.0%) underwent secondary laryngoscopic evaluation.There were 4 cases of recurrence (18.2%), with no laryngeal obstruction,bleeding, or nerve damage. Conclusion:Laryngeal stridor and dyspnea are the main clinical symptoms of lingual thyroglossal duct cysts in children. The coblation resection of lingual thyroglossal duct cysts under self-retaining laryngoscopy is safe and effective. Cyst recurrence correlates strongly with residual cyst walls, emphasizing the need for enhanced intraoperative visualization and refined surgical precision.
Humans
;
Thyroglossal Cyst/surgery*
;
Male
;
Female
;
Child
;
Retrospective Studies
;
Child, Preschool
;
Laryngoscopy/methods*
;
Treatment Outcome
;
Catheter Ablation/methods*
8.Application of P1 response threshold of cortical auditory evoked potential in rehabilitation evaluation of young children with cochlear implant.
Hui JI ; Yaofeng JIANG ; Fei ZHONG ; Baona LI ; Ye FAN ; Shiyu TAO ; Liping MENG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(10):962-966
Objective:To explore the application value of P1 response threshold of cortical auditory evoked potential(CAEP) in evaluating the rehabilitation effect of cochlear implant in young children. Methods:Thirty-three young children after cochlear implantation were divided into groups according to hearing age: Group A(hearing age 1-<2 years old) 10 people; Group B(hearing age 2-<3 years old) 13 people; Group C(hearing age 3-<4 years old) 10 people. The subjective assessment was carried out using the assessment tool for hearing-impaired children- "Criteria and Methods for assessing Auditory and language ability of hearing-impaired children" and objective electrophysiological examination was carried out using CAEP to evaluate the rehabilitation effect. SPSS 25.0 software was used for statistical analysis. Results:The results of subjective assessment of auditory ability and language ability in each group showed an increasing trend with the increase of auditory age. In this study, the P1 response threshold of CAEP in CI implanted children had a significant positive correlation with the 2 kHz hearing threshold after intervention, and the P1 response threshold of CAEP was negatively correlated with many items in subjective auditory ability and language ability assessment. Conclusion:The P1 response threshold of CAEP has a stable correlation with the results of speech audiometry, which can effectively and objectively evaluate the postoperative rehabilitation effect of young children with cochlear implantation.
Humans
;
Child, Preschool
;
Infant
;
Male
;
Female
;
Evoked Potentials, Auditory
;
Cochlear Implantation/rehabilitation*
;
Cochlear Implants
;
Auditory Threshold
9.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
10.A dual-targeting peptide-drug conjugate based on CXCR4 and FOLR1 inhibits triple-negative breast cancer.
Kun WANG ; Cong WANG ; Hange YANG ; Gong CHEN ; Ke WANG ; Peihong JI ; Xudong SUN ; Xuegong FAN ; Jie MA ; Zhencun CUI ; Xingkai WANG ; Hao TIAN ; Dengfu WU ; Lu WANG ; Zhimin WANG ; Jiangyan LIU ; Juan YI ; Kuan HU ; Hailong ZHANG ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(10):4995-5009
Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8+ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

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