1.Shaoyaotang Regulates miRNA-155-mediated SOCS1/JAK1/STAT1 Signaling Pathway to Affect Macrophage Polarization
Qi CHENG ; Bo ZOU ; Youwei XIAO ; Yiqian YU ; Ruoru HUANG ; Yan GONG ; Jiachun XIONG ; Jun XIONG ; Dichang LAI ; Dongsheng WU ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):43-52
ObjectiveTo investigate the mechanism by which Shaoyaotang regulates the miRNA-155-mediated suppressor of cytokine signaling 1 (SOCS1)/Janus kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and thereby affects macrophage polarization. MethodsThe cell-counting kit-8 (CCK-8) assay was used to detect the effect of drug-containing serum of Shaoyaotang at different concentrations on the viability of RAW 264.7 cells. A cell model of inflammation was established by stimulating RAW264.7 cells with lipopolysaccharide (LPS) at a concentration of 10 mg·L-1 The modeled cells were assigned by the random number table method into seven groups: LPS-induced M1 polarization (model), M1+miRNA-155 mimics, M1+miRNA-155 inhibitor, M1+Shaoyaotang-containing serum, M1+miRNA-155 mimics+Shaoyaotang-containing serum, M1+miRNA-155 inhibitor+Shaoyaotang-containing serum, and M1+blank serum. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)]. Immunofluorescence assay was used to detect the expression of macrophage polarization markers [inducible nitric oxide synthase (iNOS) and macrophage mannose receptor 1 (CD206)]. Real-time PCR was employed to measure the expression of miRNA-155 in cells. Western blot was performed to determine the protein levels of SOCS1, STAT1, and JAK1. ResultsCompared with the LPS-induced M1 polarization (model) group, the M1+miRNA-155 mimics group showed up-regulated expression of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS (P<0.05) and down-regulated expression of CD206 (P<0.05). In both the M1+miRNA-155 inhibitor group and the M1+Shaoyaotang-containing serum group, the expression levels of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS were down-regulated (P<0.05), while those of SOCS1 and CD206 were up-regulated (P<0.05). Compared with the M1+miRNA-155 mimics group, the M1+miRNA-155 mimics+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS (P<0.05) and up-regulated expression of SOCS1 and CD206 (P<0.05). Compared with the M1+miRNA-155 inhibitor group, the M1+miRNA-155 inhibitor+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS (P<0.05) and up-regulated expression of SOCS1 and CD206 (P<0.05). ConclusionShaoyaotang regulates macrophage polarization by modulating miRNA-155 expression and interfering with the SOCS1/JAK1/STAT1 signaling pathway. The findings provide new experimental evidence for the treatment of ulcerative colitis with Shaoyaotang.
2.Effect and Mechanisms of Shaoyaotang on Murine Ulcerative Colitis via Modulating Macrophage Glycolytic Reprogramming and Polarization Through HIF-1α Pathway
Yiqian YU ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Ruoru HUANG ; Qi CHENG ; Youwei XIAO ; Yan GONG ; Jiachun XIONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):53-60
ObjectiveTo investigate the potential role and underlying mechanisms of Shaoyaotang in intervening macrophage glycolytic reprogramming in ulcerative colitis (UC). MethodsForty-eight C57BL/6 mice were randomly divided into six groups: Normal control group, model group, mesalazine group (0.39 g·kg-1), Shaoyaotang group (15.54 g·kg-1), 2-deoxy-D-glucose (2-DG) group (glycolysis inhibitor, 100 mg·kg-1), and 2-DG + Shaoyaotang combined group (100 mg·kg-1+15.54 g·kg-1). Except for the normal control group, mice in the other five groups were induced to establish UC models using dextran sulfate sodium (DSS). The normal control group was administered pure water via intragastric gavage, while the other groups received intragastric gavage of mesalazine solution, intragastric gavage of Shaoyaotang, and the 2-DG group was treated with 2-DG via intraperitoneal injection. After 7 consecutive days of treatment, colonic tissues were extracted. Hematoxylin and eosin (HE) staining was performed to evaluate histopathological changes and tissue injury in the colon. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in colonic tissues. Western blot analysis was employed to determine the expression levels of hypoxia-inducible factor-1α (HIF-1α), glucose transporter (GLUT1), lactate dehydrogenase A (LDHA), pyruvate kinase M2 (PKM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in colonic tissues. Immunofluorescence was conducted to detect the expression of CD206 and inducible nitric oxide synthase (iNOS) in colonic tissues. Liquid chromatography-mass spectrometry (LC-MS) was utilized to measure lactate and citrate levels in colonic tissues. ResultsCompared with the normal control group, mice in the model group exhibited a significant increase in disease activity index (DAI) scores, accompanied by colonic mucosal congestion, edema, and inflammatory cell infiltration, significantly elevated expression of the inflammatory cytokine TNF-α (P<0.05), significantly decreased IL-10 expression (P<0.05), significantly increased levels of HIF-1α, GLUT1, LDHA, PKM2, and PFKFB3 in colonic tissues (P<0.05), markedly elevated iNOS expression (P<0.05), significantly decreased CD206 expression (P<0.05), and significantly elevated lactate and citrate levels in colonic tissues (P<0.05). In contrast to the model group, the Shaoyaotang group, inhibitor group, and Shaoyaotang combined with inhibitor group demonstrated amelioration of mucosal injury in colonic tissues, markely decreased expression levels of the inflammatory cytokine TNF-α (P<0.05), elevated IL-10 expression levels, significantly decreased expression of HIF-1α, GLUT1, LDHA, PKM2, and PFKFB3 (P<0.05), markedly reduced iNOS expression levels (P<0.05), significantly increased CD206 expression (P<0.05) and significantly decreased lactate and citrate levels (P<0.05). ConclusionShaoyaotang ameliorates symptoms of DSS-induced UC in mice, and its therapeutic mechanism may be associated with regulating macrophage glycolytic reprogramming via modulation of the HIF-1α signaling pathway.
3.Shaoyaotang Ameliorates Ulcerative Colitis by Regulating miR-155-5p
Ruoru HUANG ; Bo ZOU ; Yu ZHANG ; Yiqian YU ; Qi CHENG ; Youwei XIAO ; Jiachun XIONG ; Yan GONG ; Dongshen WU ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):61-68
ObjectiveTo investigate the role of microRNA-155-5p (miR-155-5p) in ulcerative colitis (UC) and study the molecular mechanism of Shaoyaotang in the treatment of UC by regulating miR-155-5p. MethodsForty-eight SPF-grade male C57BL/6 mice were selected and assigned via the random number table method into 6 groups (n=8): A blank control group, a model group, a mesalazine (0.39 g·kg-1) group, a Shaoyaotang (31.08 g·kg-1) group, a Janus kinase 1 (JAK1) inhibitor (baricitinib, 10 mg·kg-1) group, and a Shaoyaotang combined with inhibitor (baricitinib 10 mg·kg-1 + Shaoyaotang 31.08 g·kg-1) group. After successful modeling of UC by gavage of 3% dextran sulphate sodium solution, each group received corresponding drug intervention for 7 days. Shaoyaotang and mesalazine were administered by gavage, and baricitinib by intraperitoneal injection. Twenty-four hours after the last administration, mice were anesthetized by intraperitoneal injection of pentobarbital sodium, and blood was collected for determination of white blood cell count and erythrocyte sedimentation rate (ESR). Mice were then sacrificed for measurement of colon length. Hematoxylin-eosin staining was used to observe colonic pathological changes and perform pathological scoring. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the relative expression of miR-155-5p in the colonic tissue, and Western blot was used to determine the protein levels of JAK1, phosphorylated JAK1 (p-JAK1), suppressor of cytokine signaling 1 (SOCS1), signal transducer and activator of transcription 1 (STAT1), and phosphorylated STAT1 (p-STAT1). ResultsCompared with the blank control group, the model group showed increased disease activity index (DAI) score and pathological score, shortened colon, upregulated relative expression of miR-155-5p and protein levels of p-JAK1 and p-STAT1, downregulated protein level of SOCS1 in the colonic tissue, prolonged time of erythrocyte sedimentation, and increased white blood cell count (P<0.01). Compared with the model group, all drug-treated groups exhibited improvements in the above indicators (P<0.01). Moreover, the Shaoyaotang group showed better therapeutic effects than the mesalazine group in regulating miR-155-5p expression, related protein levels, DAI score, and colonic pathological score (P<0.01). ConclusionShaoyaotang may downregulate miR-155-5p to relieve its inhibition on SOCS1, thereby suppressing the excessive activation of the JAK1/STAT1 signaling pathway and ultimately alleviating intestinal inflammatory damage.
4.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
;
Body Mass Index
;
China/epidemiology*
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Rural Population/statistics & numerical data*
;
Aged
;
Follow-Up Studies
;
Adult
;
Mortality
;
Cause of Death
;
Obesity/mortality*
;
Overweight/mortality*
5.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
6.Establishment and verification of a nomogram prediction model for residual stone risk following flexible ureteroscopy lithotripsy in treating 2-3 cm renal calculi
Qi DING ; Xiaohua JIN ; Hailiang ZHU ; Cheng CAO ; Zhijiang FAN ; Wenjian TU ; Feng LI ; Bo FAN
Journal of Modern Urology 2025;30(11):967-974
Objective To develop and validate a nomogram prediction model for residual stone risk after flexible ureteroscopic lithotripsy(FURL)in patients with 2-3 cm renal calculi,so as to provide reference for treatment options.Methods Clinical data of 342 patients with renal calculi measuring 2-3 cm undergoing FURL in our hospital during Jun.2017 and Apr.2024 were retrospectively collected.At a 3∶1 randomization ratio,patients were allocated to the training cohort(n=257)and validation cohort(n=85).Patients in the training cohort were stratified into two subgroups based on postoperative stone-free status:residual stone group(n=63)and stone-free group(n=194).Logistic regression analysis was employed to identify factors influencing stone retention and construct the nomogram prediction model.Bootstrapped resampling was applied to validate the model internally,model performance was assessed with calibration curves,Hosmer-Lemeshow test was used to test the degree of fitting,receiver operating characteristic(ROC)curve was plotted to evaluate the predictive accuracy,and decision curve analysis was used to determine the clinical net benefit.The model's generalization capability was evaluated with 10-fold cross-validation of the training set.Results Multivariate logistic regression revealed that stone size,CT value,lower calyx stones,multiple stones,renal infundibulum length(RIL),and renal infundibulum width(RIW)were independent predictors of residual stones(P<0.05).The nomogram based on the above mentioned parameters demonstrated excellent discrimination,with Bootstrap-validated concordance indices of 0.876(training cohort)and 0.948(validation cohort).Hosmer-Lemeshow tests showed good calibration in both cohorts(P>0.05).ROC analysis yielded the area under the curve(AUC)of 0.876 and 0.948 for the training and validation cohorts,respectively.The optimal cutoff value was 0.253,with corresponding sensitivity of 84.13%,specificity of 78.35%,and total score of nomogram of 143.The decision curve analysis showed when the threshold probability of the training cohort and verification cohort was 0-0.81 and 0-0.97,respectively,the nomogram could obtain good clinical net benefit in predicting the risk of residual stones.The average accuracy of 10-fold cross-validation was 0.814,and the average AUC was 0.865.Conclusion The nomogram model effectively predicts residual stone risk following FURL for 2-3 cm renal calculi.It is suggested that patients with a total score of ≤143 may consider undergoing FURL.
7.Comparison of short-term and long-term outcomes of robotic versus laparoscopic gastrectomy for locally advanced gastric cancer after neoadjuvant therapy
Gan LIU ; Qi LIU ; Yulong TIAN ; Shougen CAO ; Xiaodong LIU ; Zequn LI ; Xiaojie TAN ; Cheng MENG ; Yuqi SUN ; Yanbing ZHOU
Chinese Journal of General Surgery 2025;40(8):607-612
Objective:To compare the short- and long-term outcomes of robotic versus laparoscopic gastrectomy in patients with locally advanced gastric cancer after neoadjuvant chemotherapy.Methods:Data from 321 patients with locally advanced gastric cancer undergoing neoadjuvant chemotherapy followed by robotic ( n=109) and laparoscopic ( n=212) radical gastrectomy at our center between May 2017 and Sep 2022 was collected. After 1∶1 propensity score matching, 106 patients from each group were included in the final analysis to compare short-term clinical outcomes and long-term prognostic indicators. Results:The robotic group had a significantly lower overall complication rate (13.2% vs. 28.3%, χ2=6.453, P=0.007) and surgery-related complication rate (8.5% vs. 17.9%, χ2=3.333, P=0.043) than the laparoscopic group. The robotic group also retrieved more total lymph nodes (35.3±4.9 vs. 31.4±6.3, t=4.863, P<0.001) and supra-pancreatic lymph nodes (13.1±3.4 vs. 10.1±2.1, t=5.258, P<0.001). Additionally, the robotic group had a shorter operative time [(218±47) min vs. (267±71) min, t=-6.001, P<0.001], less intraoperative blood loss [(47±12) ml vs. (71±17) ml, t=-5.424, P<0.001], and faster postoperative recovery. The 3-year recurrence-free survival rate was significantly higher in the robotic group compared to the laparoscopic group (75.5% vs. 62.3%, P=0.017). Conclusion:Compared with laparoscopic gastrectomy, robotic gastrectomy allows for a more lymph nodes harvest, significantly reduces intraoperative blood loss and complication rates and significantly improves recurrence-free survival.
8.Research on the Current Situation and Influencing Factors of Psychological Distress in Weight Loss among Middle-aged and Young Obese Patients
Meiling LIU ; Zhiqiang CHENG ; Luru LIU ; Qi WU ; Jingbo XIAO ; Jiazhen TANG ; Ying CAO
Herald of Medicine 2025;44(12):1922-1926
Objective To investigate the status and influencing factors of psychological distress associated with weight loss among young and middle-aged adults with obesity,so as to provide a theoretical basis for developing personalized interventions and improving psychological well-being.Methods A convenience sampling method was used to select young and middle-aged obese patients who visited the weight management clinic of a Grade A tertiary hospital in Jiangxi Province from October 2024 to May 2025.Data were collected using a general information questionnaire,the distress thermometer,the perceived social support scale,the brief illness perception questionnaire,and the simplified coping style questionnaire.Binary logistic regression was applied to identify factors influencing psychological distress.Results A total of 204 valid questionnaires were collected.The detection rate of significant psychological distress was 58.82%(120 cases).Regarding weight loss methods,32.84%of participants opted for medication.The top five issues reported on the psychological distress problem list were:appearance/body image,work/studies,lack of time/energy to care for elderly parents or children,bathing/dressing,and relationship with a partner.Binary logistic regression indicated that age,body mass index,waist circumference,history of chronic disease,perceived social support,illness perception,and negative coping style were significant influencing factors of psychological distress(P﹤0.05).Conclusions The rate of significant psychological distress is relatively high among young and middle-aged obese patients and is influenced by multiple factors.Medical staff may develop personalized interventions based on these factors to reduce the incidence of psychological distress.
9.Comparative of the effects of in situ repair and full-thickness repair on partial tears of the supraspinatus tendon bursa in rotator cuff tears
Liang ZHANG ; Haomiao YU ; Ruiqi CAO ; Qian CHENG ; Zhengrong QI
International Journal of Surgery 2025;52(11):742-746
Objective:To compare the efficacy of in situ repair and conversion to full-thickness repair in patients with partial tears of the supraspinatus tendon bursa side in rotator cuff tears. Methods:A retrospective analysis was performed on 81 patients who underwent shoulder arthroscopic surgery due to Ellman grade III partial tears on the rotator cuff bursa side in Beijing Friendship Hospital, Capital Medical University from January 2021 to December 2022, according to the different intraoperative supraspinatus tendon repair methods, the patients were divided into the in situ repair group ( n=44) and the partial-to-full-thickness repair group ( n=37). Patients in the in situ repair group were treated with in situ repair for supraspinatus tendon repair, while those in the partial-to-full-thickness repair group were treated with partial-to-full-thickness repair for supraspinatus tendon repair. The general information, pain visual analogue scale (VAS) score, University of California, Los Angeles (UCLA) shoulder joint score and Constant score of the patients were compared and analyzed; the operation time, number of anchors used, and rotator cuff re-tear rate 1 year after surgery were compared and analyzed. The measurement data were expressed as mean ± standard deviation ( ± s), and comparisons between groups were performed using the independent samples t-test. The count data were expressed as the number of cases and percentages, and comparisons between groups were performed using the Chi-square test. Results:All 81 patients completed the follow-up. One year after surgery, the pain VAS scores of the in situ repair group and the partial-to-full-thickness repair group were 1.48±1.07 and 1.38±0.83, respectively, with no significant statistical difference ( P=0.647). The UCLA shoulder joint score and Constant score in the in situ repair group were 30.09±1.46 and 83.05±10.94, respectively, and those in the partial-to-full-thickness repair group were 30.46±1.04 and 84.95±9.20, respectively, there were no significant statistical difference ( P=0.203, 0.405). There was no significant statistical difference in the operation time between the in situ repair group and the partial-to-full-thickness repair group ( P=0.276), but the partial-to-full-thickness repair group was about 11.5 min slower on average. The number of anchors used in the in situ repair group (1.86±0.88) was significantly less than that in the partial-to-full-thickness repair group (2.51±0.65), and the difference was statistically significant ( P<0.001). There was no significant statistical difference in the re-tear rate between the two groups 1 year after surgery ( P=0.625). Conclusions:For patients with partial tears of the supraspinatus tendon bursa side in rotator cuff tears, both in situ repair and partial-to-full-thickness repair can achieve good clinical results, but conversion to full-thickness repair requires longer operation time and more anchors. The choice of specific surgical method needs to be determined based on the patient′s condition and the doctor′s technical proficiency.
10.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

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