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 among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students
Xiang WANG ; Xiaojing ZHOU ; Shali QIU ; Yuheng ZANG ; Peng WANG ; Jing WANG ; Jinlei ZHAO ; Xin XIN ; Qun ZHAO ; Suowang YIN ; Xing WANG
Chinese Mental Health Journal 2024;38(2):180-185
Objective:To investigate the correlation among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students.Methods:Seventy college students with mild depressive symp-toms who conformed to the standard of the Self-Rating Scale for Depression(SDS)of 53-62 and 70 normal col-lege students were recruited.The frontal alpha power was measured under quiet and closed-eye state,and the total physical activity(PA)was assessed with the International Physical Activity Questionnaire.Results:The college students with mild depressive symptoms had lower Total PA scores,right frontal alpha power and frontal alpha a-symmetry(FAA)than the normal controls(P<0.001).In college students with mild depressive symptoms,the to-tal PA scores(r=-0.29,P<0.05)and FAA(r=-0.41,P<0.001)were negatively correlated with SDS scores,and the total PA scores were positively correlated with FAA(r=0.34,P<0.01).Conclusion:The college students with mild depressive symptoms may have reduced physical activity and asymmetric right lateralization of frontal alpha power.There is a correlation among depressive symptoms,physical activity and frontal alpha power a-symmetry in college students with mild depressive symptoms.
3.Advances of Neoadjuvant Targeted Therapy in ALK-positive Non-small Cell Lung Cancer.
Weizhen SUN ; Yuheng ZHOU ; Yaobin LIN ; Shoucheng FENG ; Hao LONG
Chinese Journal of Lung Cancer 2024;27(11):849-854
Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer-related death worldwide, with anaplastic lymphoma kinase (ALK) fusion mutations accounting for approximately 4%-9% of cases. In recent years, there are increasing clinical evidences suggesting that the combination of ALK inhibitors with surgical treatment holds significant potential for clinical application in resectable early and locally advanced non-small cell lung cancer (NSCLC) patients. This review aims to summarize the advances in neoadjuvant targeted therapy for ALK fusion positive NSCLC and discuss its advantages and challenges in clinical practice.
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Humans
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Carcinoma, Non-Small-Cell Lung/enzymology*
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Anaplastic Lymphoma Kinase/antagonists & inhibitors*
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Lung Neoplasms/enzymology*
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Neoadjuvant Therapy/methods*
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Molecular Targeted Therapy
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Protein Kinase Inhibitors/therapeutic use*
4.Clinical characteristics and treatment of central nervous system aspergillosis: an analysis of 37 cases
Ruishu TAN ; Jiatang ZHANG ; Yuheng SHAN ; Yubao MA ; Lei WU ; Hu YUAN ; Lei CHEN ; Tao ZHOU ; Liping ZOU ; Jian ZHU ; Quangang XU ; Shengyuan YU
Chinese Journal of Neurology 2023;56(1):55-65
Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.
5.Practice and Thinking of Promoting Spiritual Culture Cultivation by Inheriting the Red Gene in Public Hospital
Qi JIN ; Litao JIA ; Yuheng CHEN ; Yan ZHOU ; Ping ZHANG
Chinese Medical Ethics 2023;36(2):211-215
The red gene is the crystallization of the ideas and wisdom of the Chinese Communist Party’s century-long struggle, and plays an irreplaceable and decisive role in cultivating socialist hospital culture and medical professionals in the new era. The Chinese Academy of Medical Science (CAMS) Cancer Hospital has a distinctive red gene trait. For more than 60 years since its establishment, through the protection of the red gene inheritance carrier, the enrichment of the content and expression form of the red gene inheritance, and the exploration and demonstration of the role model in the red gene inheritance, it has always integrated the red gene inheritance into the whole process of hospital construction, development and spiritual culture cultivation, and has achieved remarkable results, accumulated rich practical experience, and provided a useful reference for the spiritual and cultural construction of public hospitals.
6.Recent HIV infection and associated factors among men who have sex with men in Jiangsu province
Haiyang HU ; Yuheng CHEN ; Ying ZHOU ; Zhi ZHANG ; Jing LU ; Xiaoyan LIU ; Liping CHEN ; Gengfeng FU
Chinese Journal of Epidemiology 2021;42(11):1989-1993
Objective:To understand the incidence of HIV infections and associated factors among men who have sex with men (MSM) in Jiangsu province.Methods:Based on national AIDS sentinel surveillance in 2019, MSM from 13 cities in Jiangsu were recruited for questionnaire interview and laboratory testing during April to July, 2019. Seropositive samples were tested with Limiting-antigen avidity enzyme immunoassay to detect recent HIV infections. The incidence of HIV infection in MSM were calculated according to the formula and parameters from China CDC. Multivariable logistic regression analysis was used to identify factors associated with recent infection of HIV.Results:A total of 4 469 MSM were subjects and the incidence of HIV infection were 4.5% (95% CI: 3.4%-5.5%).Multivariate logistic regression analysis results showed that compared with these aged ≥40 years, recruitment ways from MSM venues, awareness of AIDS knowledge, non-unprotected anal sex in the past 6 months and non-syphilis infection, those who aged 18-24 years (a OR=2.083,95% CI:1.087-3.990), recruitment ways from VCT clinics (a OR=2.125,95% CI:1.175-3.843), unawareness of AIDS knowledge (a OR=2.456,95% CI:1.109-5.437), unprotected anal sex in the past 6 months (a OR=3.553,95% CI:2.143-5.889) and syphilis infection (a OR=2.414,95% CI:1.033-5.462) were higher risk of HIV infection. Conclusion:The new infection rates of HIV were high in MSM in Jiangsu province. Health education, condom use and HIV/syphilis screening promotions should therefore be top priority in the prevention and control of HIV infection in MSM.
7.Evaluation on the effect of clinic standardized blood pressure measurement model applying to first blood pressure measurement among community population aged 35 years old and above
Qinghua YAN ; Jie YU ; Yuheng WANG ; Jiabao GAO ; Feng ZHOU ; Yan WANG ; Dingliang ZHU ; Yan SHI ; Minna CHENG ; Yejing WANG
Chinese Journal of Preventive Medicine 2020;54(4):416-419
Objective:To evaluate the effect of clinic standardized blood pressure measurement model (SBPM) applying to first blood pressure measurement among community population aged 35 years old and above.Methods:SBPM was implemented in the community health service center of Dapuqiao street, Huangpu district of Shanghai from June 1, 2018, and the data between June 1 and December 31, 2018 was used as the SBPM data. The first-diagnosis blood pressure measurement data in this center between June 1 and December 31, 2017 was used as the conventional measurement (CM) model data. The detection rate of elevated blood pressure under SBPM was standardized according to the gender and age distribution of subjects in CM. The equilibrium of the value distribution of the end digit of blood pressure value in different pressure-measuring models and difference of elevated blood pressure rate of subjects with different characteristics and seasons were analyzed by using the χ 2 test, and the difference of standardized elevated blood pressure rate in different pressure-measuring models was analyzed by using the U test. Results:The SBPM included 1 548 subjects and 639 (41.28%) of them were males. The CM included 2 952 inpatients and 1 196 (40.51%) of them were males. The frequency of the end digit of blood pressure in SBPM ranged from 9.04% to 10.72%, and both systolic and diastolic blood pressure showed a balanced distribution of end digit ( P values were 0.996 and 0.981 respectively). The frequency of blood pressure end digital in the CM ranged from 0.37% to 67.92%, and both systolic and diastolic blood pressure showed an unbalanced distribution (both P values <0.001). The crude rate and standardized elevated blood pressure rate in SBPM were 23.19% (359/1 548) and 23.05%, which were higher than that in CM, about 7.22% (213/2 952) (both P values <0.001). The elevated blood pressure rate in SBPM in summer, autumn and winter was 18.85% (141/748), 26.72% (152/591) and 31.58% (66/209), respectively, which was higher than that in CM, about 6.28% (91/1 450), 7.20% (82/1 139) and 11.02% (40/363), respectively (all P values <0.001). Conclusion:The quality of blood pressure data and the efficiency of hypertension screening of SBPM are better than those of CM when applying to first blood pressure measurement among community population aged 35 years old and above.
8.Evaluation on the effect of clinic standardized blood pressure measurement model applying to first blood pressure measurement among community population aged 35 years old and above
Qinghua YAN ; Jie YU ; Yuheng WANG ; Jiabao GAO ; Feng ZHOU ; Yan WANG ; Dingliang ZHU ; Yan SHI ; Minna CHENG ; Yejing WANG
Chinese Journal of Preventive Medicine 2020;54(4):416-419
Objective:To evaluate the effect of clinic standardized blood pressure measurement model (SBPM) applying to first blood pressure measurement among community population aged 35 years old and above.Methods:SBPM was implemented in the community health service center of Dapuqiao street, Huangpu district of Shanghai from June 1, 2018, and the data between June 1 and December 31, 2018 was used as the SBPM data. The first-diagnosis blood pressure measurement data in this center between June 1 and December 31, 2017 was used as the conventional measurement (CM) model data. The detection rate of elevated blood pressure under SBPM was standardized according to the gender and age distribution of subjects in CM. The equilibrium of the value distribution of the end digit of blood pressure value in different pressure-measuring models and difference of elevated blood pressure rate of subjects with different characteristics and seasons were analyzed by using the χ 2 test, and the difference of standardized elevated blood pressure rate in different pressure-measuring models was analyzed by using the U test. Results:The SBPM included 1 548 subjects and 639 (41.28%) of them were males. The CM included 2 952 inpatients and 1 196 (40.51%) of them were males. The frequency of the end digit of blood pressure in SBPM ranged from 9.04% to 10.72%, and both systolic and diastolic blood pressure showed a balanced distribution of end digit ( P values were 0.996 and 0.981 respectively). The frequency of blood pressure end digital in the CM ranged from 0.37% to 67.92%, and both systolic and diastolic blood pressure showed an unbalanced distribution (both P values <0.001). The crude rate and standardized elevated blood pressure rate in SBPM were 23.19% (359/1 548) and 23.05%, which were higher than that in CM, about 7.22% (213/2 952) (both P values <0.001). The elevated blood pressure rate in SBPM in summer, autumn and winter was 18.85% (141/748), 26.72% (152/591) and 31.58% (66/209), respectively, which was higher than that in CM, about 6.28% (91/1 450), 7.20% (82/1 139) and 11.02% (40/363), respectively (all P values <0.001). Conclusion:The quality of blood pressure data and the efficiency of hypertension screening of SBPM are better than those of CM when applying to first blood pressure measurement among community population aged 35 years old and above.
9.Establishment of a Stable Cell Line Overexpressing Human SAMHD1 Gene and Its Antiviral Activity
Jinying WU ; Zhou ZHANG ; Ziwei LI ; Haoran WANG ; Sunrun CAO ; Yuheng LI ; Xiaoyu SONG ; Liu CAO
Journal of China Medical University 2019;48(2):128-131,143
Objective A lentivirus-mediated colon cancer cell line stably overexpressing human SAMHD1 gene was constructed to observe the effect of this gene on the ability of the cells to resist herpes simplex virus type 1 (HSV-1) infection. Methods p CDH-EF1-MCS-SAMHD1-T2 A-GFP recombinant plasmid was constructed using pCDH-EF1-MCS-T2 A-copGFP lentiviral vector. After confirming successful synthesis with sequencing, the recombinant plasmid and lentivirus packaging plasmids were co-transfected into 293 T cells. The pseudovirus solution was collected and concentrated, then human colon cancer cells were infected with the concentrated solution. The cell line overexpressing SAMHD1 gene was infected with HSV-1 in contrast to the control group, and the virus infection efficiency was assessed by Western blotting and immunofluorescence analyses. Results The pCDH-EF1-MCS-SAMHD1-T2 A-GFP recombinant plasmid was successfully constructed and verified by gene sequencing. Western blotting confirmed the overexpression of the SAMHD1 gene with higher levels of the gene in the transfected cells in contrast to control human colon cancer cell line. Western blotting and immunofluorescence showed that the cell line overexpressing human SAMHD1 gene could effectively inhibit the infection of HSV-1. Conclusion Lentivirus-mediated stable cell line overexpressing human SAMHD1 gene was effective in inhibiting HSV-1 replication and could help us to further investigate the function of SAMHD1.
10.A prospective cohort study on reducing perioperative fasting in traumatic patients following Enhanced Recovery After Surgery protocol
Ting LI ; Yan ZHOU ; Xu SUN ; Zhijian SUN ; Yuheng JIANG ; Xuemei LU ; Guiling PENG ; Chunling ZHANG ; Yao JIANG ; Shengnan SUN ; Chen YI ; Yan AN ; Han WANG ; Bing HAN ; Geng WANG ; Xinbao WU
Chinese Journal of Orthopaedic Trauma 2018;20(4):312-317
Objective To evaluate the effectiveness of perioperative fasting abbreviation in traumatic patients undergoing selective surgeries.Methods The traumatic patients undergoing selective surgeries from November 2016 to January 2017 at our department were selected for this prospective cohort study.They were divided into an intervention group (69 patients) and a control group (121 patients) according to the wards where they stayed.The intervention group was fasted for solids 6 hours prior to surgery and received oral solution with maltodextrin 2 hours prior to surgery.After surgery,they were allowed to drink liquids as soon as they were awakened.Normal food was allowed 2 hours later.The control group was fasted for either liquids or solids the night before surgery.After surgery,the patients who had received brachial plexus block only were allowed liquids with no limitation while the other patients were allowed liquids 6 hours after surgery and then were free for solids and liquids if no discomfort was observed.The time periods for preoperative liquids and solids fasting and for postoperative intake of liquids and solids were recorded and compared between the 2 groups.The perioperative well-beings (including anxiety,thirst,hunger,nausea,fatigue,dizziness,sweating and stomach discomfort) and serum glucose levels were compared between the 2 groups.Adverse reactions were observed.Results The preoperative fasting time for liquids for the intervention group (4.5 ± 2.9 hours) was significantly shorter than that for the control group (14.3 ±3.9 hours) (P < 0.05).The preoperative fasting time for solids for the intervention group (17.6 ± 3.0 hours) were significantly longer than that for the control group (16.1 ±3.8 hours) (P < 0.05).The postoperative fasting time periods for both liquids [1 (0,3) h] and solids [2 (1,4) h] for the intervention group were significantly shorter than those for the control group [6(6,6) h] hours and [6(6,6) h] (P < 0.05).Compared with the control group,the perioperative anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort were significantly improved in the intervention group (P < 0.05).The average serum glucose level was similar in both groups upon admission (P < 0.05);it was significantly higher in the intervention group immediately before surgery (P < 0.05) but was gradually decreased after surgery until there was no significant difference between the 2 groups (P > 0.05).No major adverse reaction was observed in either group.Conclusion The protocol of perioperative fasting abbreviation may be safe and feasible in traumatic patients for selective surgeries,showing benefits of decreased anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort.

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