1.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.
2.Relationship between autonomous rehabilitation behavior and related symptoms of middle-aged stroke patients
Yuting TAN ; Zhixia ZHANG ; Mengli XU ; Peiran GUO ; Qin XIAO ; Linru QIAO ; Feiyun SONG ; Qiaojun YU
Chinese Journal of Nursing 2025;60(7):773-778
Objective To explore the time-varying characteristics and correlation degree of autonomous rehabili-tation behavior and related symptoms of middle-aged stroke patients,and to provide a basis for clinical transitional nursing and precise rehabilitation.Methods Ecological momentary assessment was used to select 57 middle-aged stroke patients who underwent rehabilitation treatment in the Rehabilitation Medicine Department of a tertiary com-prehensive hospital in Wuhan from March 15 to August 30,2024,using convenience sampling method.Their au-tonomous rehabilitation behavior and related symptoms(fatigue,pain,emotion,sensation)were continuously monitored for 2 weeks.A hierarchical linear model was used to analyze the correlation between behavior and symptoms.Results The autonomous rehabilitation behavior of middle-aged stroke patients showed a fluctuating increasing trend,and the symptom score showed a slow decreasing trend.The hierarchical linear model showed that compared with female patients,male patients have longer duration of autonomous rehabilitation behavior(P<0.05).The number and duration of autonomous rehabilitation behaviors in patients without fatigue were higher(P<0.05).The number of autonomous rehabilitation behaviors in patients without pain was higher than that in patients with pain(P<0.05).The number of autonomous rehabilitation behavior items among patients who perceived more pleasure in rehabilitation was higher than that among patients with greater difficulty in rehabilitation challenges(P<0.05).Patients with high rehabilitation confidence have higher numbers and duration of autonomous rehabilitation behaviors compared to pa-tients with low rehabilitation confidence(P<0.05).Conclusion There are significant individual differences and dy-namic changes in the autonomous rehabilitation behavior and related symptoms of middle-aged stroke patients.Nurs-ing staff should accurately implement personalized rehabilitation services during the transition period,enhance pa-tients'autonomy and self-management ability in home-based rehabilitation,in order to improve the overall rehabilita-tion effect.
3.Relationship between autonomous rehabilitation behavior and related symptoms of middle-aged stroke patients
Yuting TAN ; Zhixia ZHANG ; Mengli XU ; Peiran GUO ; Qin XIAO ; Linru QIAO ; Feiyun SONG ; Qiaojun YU
Chinese Journal of Nursing 2025;60(7):773-778
Objective To explore the time-varying characteristics and correlation degree of autonomous rehabili-tation behavior and related symptoms of middle-aged stroke patients,and to provide a basis for clinical transitional nursing and precise rehabilitation.Methods Ecological momentary assessment was used to select 57 middle-aged stroke patients who underwent rehabilitation treatment in the Rehabilitation Medicine Department of a tertiary com-prehensive hospital in Wuhan from March 15 to August 30,2024,using convenience sampling method.Their au-tonomous rehabilitation behavior and related symptoms(fatigue,pain,emotion,sensation)were continuously monitored for 2 weeks.A hierarchical linear model was used to analyze the correlation between behavior and symptoms.Results The autonomous rehabilitation behavior of middle-aged stroke patients showed a fluctuating increasing trend,and the symptom score showed a slow decreasing trend.The hierarchical linear model showed that compared with female patients,male patients have longer duration of autonomous rehabilitation behavior(P<0.05).The number and duration of autonomous rehabilitation behaviors in patients without fatigue were higher(P<0.05).The number of autonomous rehabilitation behaviors in patients without pain was higher than that in patients with pain(P<0.05).The number of autonomous rehabilitation behavior items among patients who perceived more pleasure in rehabilitation was higher than that among patients with greater difficulty in rehabilitation challenges(P<0.05).Patients with high rehabilitation confidence have higher numbers and duration of autonomous rehabilitation behaviors compared to pa-tients with low rehabilitation confidence(P<0.05).Conclusion There are significant individual differences and dy-namic changes in the autonomous rehabilitation behavior and related symptoms of middle-aged stroke patients.Nurs-ing staff should accurately implement personalized rehabilitation services during the transition period,enhance pa-tients'autonomy and self-management ability in home-based rehabilitation,in order to improve the overall rehabilita-tion effect.
5.Clinical application of branch artery of the sural medial gastrocnemius muscle flap combine with sural nerve nutritional vessel axial
Xinzhong SHAO ; Weiguang YU ; Qiaojun WANG ; Yingcai WANG ; Li LV ; Li WANG ; Jiantao SUN
Chinese Journal of Microsurgery 2011;34(5):373-375
Objective To investigate the clinical efficiency of branch artery of the sural medial gastrocnemius muscle flap combine with sural nerve nutritional vessel axial.Methods From February 2006to March 2010,according to the position and size of the soft tissue defects,the muscle flap combined with branch artery of the sural medial gastrocnemius and sural nerve nutritional vessel axial were desingned and obtained to repair 7 cases of sofi tissue defects of the upper-region of the tibial.The flap size ranged from 8.0 cm × 8.0 cm to 12.0 cm × 10.0 cm.The vessel pedicle of branches ranged from 1.8-3.0 cm.The distribution of the vessel pedicle of branches ranged from 10.0-17.0 cm on the distant popliteal fossa,and ranged from 2.0-5.0 cm on the back of medial line.Results The outline and function were satisfactory during 6-15 months follow-up.Conclusion The blood supply of this flap is reliable without sacrifice of major arteries.Flap elevation is easy.It can transfer to a long distance and can repair large skin defects.It is very useful in repairing upper-region of the tibial large soft tissue defect.
6.Selective prostaglandins EP_1 receptor antagonist inhibits afferent activity of Cunit of saphenous nerve in diabetic rats
Qiaojun ZHANG ; Shuqi YU ; Yong WANG ; Li XIANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2004;0(05):-
Objective To observe the effect o f selective prostaglandins EP 1 receptor antagonist SC19220 on the afferent activity of C unit in the saphenous nerve of diabetic rats. Methods The response of C units to sustained 1 min threshol d and suprathreshold stimuli was measured following intradermal injection of EP 1 receptor antagonist SC19220 into the receptive field of C unit of the sa phenous nerve in control and diabetic rats. Results The mechanical threshold of C units in diabetic rat s was obviously decreased compared with that of control rats (P
7.The relieving effect of cyclooxygenase inhibitors and prostaglandin receptor blocker on hyperalgesia of diabetic rats
Qiaojun ZHANG ; Yong WANG ; Feng ZHANG ; Shuqi YU
Journal of Xi'an Jiaotong University(Medical Sciences) 2003;0(06):-
Objective To observe the effects of cyclooxygenase (COX) inhibitors and prostaglandin (PG) receptor blocker on hyperalgesia of diabetic rats. Methods Nociceptive paw-withdrawal threshold (NPWT) and thermal latency (TL) of diabetic hyperalgesic rats were tested after subcutaneous injections of COX inhibitors indomethacin and meloxicam, and EP 1 PG receptor blocker SC-19220 into the dorsum of the hindpaw of the rats. Results Indomethacin, a classic inhibitor of COX, produced a significant and long-lasting relief of mechanical hyperalgesia in diabetic hyperalgesic rats. Meloxicam, a selective cyclooxygenase 2 (COX-2) inhibitor, alleviated mechanical and thermal hyperalgesia, but with a shorter duration. SC-19220, a selective EP 1 PG receptor blocker, produced significant relief of mechanical and thermal hyperalgesia. Conclusion COX inhibitors and EP 1 PG receptor blocker relieve hyperalgesia of diabetic rats, which suggests that PGs play an important role in inducing and maintaining hyperalgesia in diabatic rats.

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