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.

Objective To evaluate the gap between China's top-tier medical institutions and top-tier international medical institutions,and to provide references for the construction of first-class medical science discipline in China.Methods Using globally recognized rankings of medical institutions,we selected 24 top-tier international medical institutions and 11 top-tier Chinese medical institutions.Publicly available,general,and comparable data on indicators were collected to analyze the performance and gaps between top-tier international and Chinese medical institutions in human resources development,talent cultivation,scientific research,social services,and discipline construction.Results In the field of medicine,the largest gap between top-tier international and Chinese medical institutions was in high-level talent.Specifically,the average numbers of individuals who are Clarivate Analytics'Highly Cited Researchers,who are Nobel Prize laureates in Physiology or Medicine,and who serve on advisory boards or editorial boards of top medical journals,and who rank among the Top 2 000 Medicine Scientists were 1.00,0.09,0.45 and 4.00,respectively,among top-tier Chinese medical institutions,while those of the top-tier international medical institutions were 131.46,118.25,9.72,and 6.76 times,respectively,those of the Chinese medical institutions.The second largest gap was in social services and medical innovation.The average proportion of industrial collaboration papers and the number of clinical trials of China's top-tier medical institutions were 1.51％and 1 851,respectively,while those of international top-tier medical institutions were 3.62 and 1.87,times,respectively,those of top-tier Chinese medical institutions.However,the average number of(untranslated)patents held by top-tier international medical institutions was only 15％ of that of China's top-tier medical institutions.The third largest gap was in scientific research.The average number of papers published in New England Journal of Medicine,Journal of the American Medical Association,The Lancet,and British Medical Journal,the percentage of hot papers in papers included in Web of Science,the percentage of highly cited papers,the percentage of international collaboration papers,the total number of citations per paper,category normalized citation impact(CNCI),and the number of publications of top-tier Chinese medical institutions were 78,0.03％,1.39％,22.55％,19.61,1.26,30 706,while those of the top-tier international medical institutions were 6.96,2.66,2.57,2.15,1.83,1.58 and 1.54 times those of the Chinese medical institutions,respectively.However the average percentage of zero-citation papers of top-tier international medical institutions was only 71％of that of China's top-tier medical institutions.Furthermore,in discipline development,the average overall scores of the Times Higher Education(THE)and QS rankings for medicine-related disciplines of top-tier Chinese medical institutions were 72.84 and 69.30,respectively,while those of top-tier international medical institutions were 1.38 and 1.21 times those of the Chinese medical institutions.However,in terms of talent cultivation,the average number of students of China's top-tier medical institutions was 10724,which is roughly double that of international institutions.Conclusion Currently,China's top-tier medical institutions are still in a basic stage that emphasizes the quality of talent cultivation and medical services.There is considerable room for development and potential for catching up in multiple aspects,especially in high-level talent,medical research,and innovation.It is recommended that the construction experience of top-tier international medical institutions should be fully utilized to build China's first-class medical science discipline.

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.

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.