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.Human immunodeficiency virus complicated with acute lymphoblastic leukemia: a case report and review of the literature
Qiuqiu ZHANG ; Linyu YUAN ; Xinxiao LU ; Xue WANG ; Xiaosi JIANG ; Junshi ZHANG ; Xingli ZHAO
Clinical Medicine of China 2024;40(4):298-301
Objective:To explore the diagnosis and treatment of HIV infection complicated with acute lymphoblastic leukemia.Methods:The diagnosis and treatment of a patient with HIV infection and ALL who was admitted to Tianjin People's Hospital on February 13, 2021 were retrospectively analyzed, and the experience was summarized and the literature was reviewed.Results:The patient had a history of HIV infection for more than 3 years, and was diagnosed as acute lymphoblastic leukemia, and was treated with VCP (Vindesine 2 mg on days 1, 8, 15, 22, cyclophosphamide 600 mg on days 1-2, 15-16, dexamethasone 9 mg on days 1-14, 5 mg. 15-28 days) and died on the 8th day of chemotherapy. The cause of death was infection.Conclusion:Combined chemotherapy and hematopoietic stem cell transplantation on the basis of highly active antiretroviral therapy can improve the prognosis and survival rate of HIV-infected patients with acute lymphoblastic leukemia.
3.Effects of perioperative whole course thermal insulation strategy on extubation, recovery time, coagulation index and the incidence of complications in patients undergoing thoracoscopic surgery
Beilei XIE ; Yan ZHANG ; Qiuqiu CHEN ; Fenna ZHOU ; Qinmei SUN ; Lu HUANG
Chinese Journal of Primary Medicine and Pharmacy 2021;28(4):554-557
Objective:To investigate the effects of perioperative whole course thermal insulation strategy on extubation, recovery time, coagulation index and the incidence of complications in patients undergoing thoracoscopic surgery.Methods:A total of 121 patients who underwent thoracoscopic surgery who received treatment in Zhoushan Hospital from October 2016 to February 2018 were included in this study. Among them, 59 patients who underwent thoracoscopic surgery from October 2016 to February 2017 were included in the simple thermal insulation group, and 62 patients who underwent thoracoscopic surgery from October 2017 to February 2018 were included in the whole process thermal insulation group. Before and 24 hours and 72 hours after surgery, platelet count, prothrombin time, activated partial thromboplastin time and thrombin time were compared between the two groups. Postoperative extubation time and recovery time were recorded. The incidence of shivering, restlessness and other complications was analyzed.Results:Postoperative extubation time and recovery time in the whole process thermal insulation group were significantly shorter than those in the simple thermal insulation group [(8.06 ± 4.60) min vs. (13.98 ± 7.22) min, (47.19 ± 12.97) min vs. (56.84 ± 17.49) min, t = 5.40, 3.47, both P < 0.05). At 24 and 72 hours after surgery, platelet count and activated partial prothrombin time in the whole process thermal insulation group were significantly shorter than those in the simple thermal insulation group [(12.55 ± 0.88) s vs. (13.11 ± 0.97) s, (27.44 ± 2.43) s vs. (29.03 ± 2.14) s, (11.42 ± 0.73) s vs. (11.87 ± 0.74) s, (27.44 ± 1.96) s vs. (28.80 ± 2.22) s, t = 3.32, 3.81, all P < 0.05). The incidence of postoperative shivering and restlessness in the whole process thermal insulation group was significantly lower than that in the simple insulation Group (7 cases vs. 27 cases, 5 cases vs. 22 cases, χ2 = 17.782, 14.894, 3.33, 3.57, all P < 0.05). Conclusion:Perioperative whole course thermal insulation strategy can shorten extubation and recovery time, inhibit perioperative coagulation dysfunction, and decrease the incidence of perioperative restlessness, shivering and other complications caused by hypothermia. The effect of perioperative whole course thermal insulation is superior to that of simple thermal insulation.

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