1.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
2.Polarity-extended Liquid Chromatography-Mass Spectrometry System for Prostate Cancer Biomarker Screening Based on Extracellular Vesicles
Lu-Lu XIAO ; Meng-Xuan CHEN ; Shan-Shan PAN ; Yi-Chen WANG ; Tao-Hong HUANG ; Qi-Sheng ZHONG ; Yong CHEN ; Teng-Fei XU ; Jia-Hui ZHAO ; Xue-Song LIU
Chinese Journal of Analytical Chemistry 2025;53(11):1848-1859,中插4-中插29
Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.
3.Research progress on mechanism of curcumin in treatment of depression
Lin WANG ; Qi-fei PAN ; Wen-juan LONG ; Jia-rong DU ; Zhong-yang HU ; Xin-yao LI ; Yi-shu CHEN ; Dong-dong QIN ; Xiao-man LYU
Chinese Pharmacological Bulletin 2025;41(9):1618-1623
Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.
4.Establishment of a LC-MS/MS method for detecting gamma-aminobutyric acid in plasma and its clinical application
Jia-qian QIN ; Lei CAO ; Ying-fei PENG ; Fang-jun CHEN ; Bai-shen PAN ; Bei-li WANG ; Wei GUO
Fudan University Journal of Medical Sciences 2025;52(5):708-716
Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.
5.Research progress on mechanism of curcumin in treatment of depression
Lin WANG ; Qi-fei PAN ; Wen-juan LONG ; Jia-rong DU ; Zhong-yang HU ; Xin-yao LI ; Yi-shu CHEN ; Dong-dong QIN ; Xiao-man LYU
Chinese Pharmacological Bulletin 2025;41(9):1618-1623
Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.
6.Establishment of a LC-MS/MS method for detecting gamma-aminobutyric acid in plasma and its clinical application
Jia-qian QIN ; Lei CAO ; Ying-fei PENG ; Fang-jun CHEN ; Bai-shen PAN ; Bei-li WANG ; Wei GUO
Fudan University Journal of Medical Sciences 2025;52(5):708-716
Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.
7.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
8.Trends of age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019.
Ning MA ; Di SHI ; Shan CAI ; Jia Jia DANG ; Pan Liang ZHONG ; Yun Fei LIU ; Jing LI ; Yan Hui DONG ; Pei Jin HU ; Bin DONG ; Tian Jiao CHEN ; Yi SONG ; Jun MA
Chinese Journal of Preventive Medicine 2023;57():36-41
Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.
9.Long-term trend of the age of spermarche and its association with nutritional status among Chinese Han boys aged 11-18 from 2010 to 2019.
Di SHI ; Ning MA ; Yun Fei LIU ; Jia Jia DANG ; Pan Liang ZHONG ; Shan CAI ; Li CHEN ; Yan Hui DONG ; Pei Jin HU ; Yi SONG ; Jun MA ; Jing LI
Chinese Journal of Preventive Medicine 2023;57():42-48
Objective: To analyze the long-term trend of the age of spermarche among Chinese Han boys aged 11 to 18 from 2010 to 2019 and its association with nutritional status. Methods: The data from Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019 were used. The age, residence and spermarche of the participants were collected by questionnaire, and their height and weight were measured. A total of 184 633 Han boys aged 11‒18 years with complete data on spermarche, height, and weight were included in this study. The probability regression method was used to calculate the median age (95%CI) at spermarche in different areas, and the trend of age at spermarche in different groups was compared. The multivariate logistic regression model was used to analyze the association between nutritional status and spermarche of Chinese Han boys aged 11‒18 years. Results: The median age of spermarche (95%CI) was 13.85 (13.45-14.22) years old among Chinese Han boys aged 11‒18 years in 2019, with 0.18 years earlier than that in 2010. The median age at spermarche in urban and rural boys was 13.89 and 13.81 years, respectively. Compared with that in 2010, the age at spermarche in urban and rural boys was 0.08 and 0.27 years earlier, respectively. After adjusting for age, province and urban/rural areas, compared with normal weight, spermarche was negatively associated with wasting and positively associated with overweight and obesity, with OR (95%CI) about 0.73 (0.67-0.80), 1.09 (1.02-1.17) and 1.09 (1.01-1.18), respectively. Conclusion: The age of spermarche generally shows an advanced trend among Chinese Han boys and is associated with nutritional status.
10.Trend of the detection rate of myopia among Chinese Han children and adolescents aged 7-18 years from 2010 to 2019.
Pan Liang ZHONG ; Ning MA ; Yun Fei LIU ; Jia Jia DANG ; Di SHI ; Shan CAI ; Li CHEN ; Jie Yu LIU ; Yan Hui DONG ; Bin DONG ; Pei Jin HU ; Jun MA ; Yi SONG
Chinese Journal of Preventive Medicine 2023;57():20-26
Objective: To analyze the trend of the detection rate of myopia among Chinese Han children and adolescents aged 7-18 years from 2010 to 2019. Methods: Data from the Chinese National Survey on Students' Constitution and Health in 2010, 2014 and 2019 were used, and about 213 833, 212 742 and 209 942 Han students aged 7-18 years were included in this study. The χ² test was used to compare the differences in the prevalence of myopia among the subgroups in the survey year, and logistic regression was used to compare the differences in the prevalence of myopia between different years. A curve-fitting method was used to obtain the growth rate of myopia among Han Chinese students from 2010 to 2019, and the differences in the change of myopia between different age groups were analyzed. Results: In 2019, the overall detection rate of myopia among Chinese Han children and adolescents aged 7-18 was 60.1%. The detection rate of urban students (62.7%) was higher than that of rural students (57.4%) and the detection rate of girls (63.5%) was higher than that of boys (56.7%). In 2019, the regional disparities were large in the detection rate of myopia in various provinces, with the lowest in Guizhou (49.6%) and the highest in Zhejiang (71.3%). The detection rate of myopia showed an upward trend from 2010 to 2019, from 55.5% in 2010 to 57.1% in 2014, and finally to 60.1% in 2019. The gap in the detection rate of myopia between urban and rural children and adolescents gradually shrank. The average annual growth rate of myopia detection rate from 2014 to 2019 was 0.6 percentage points per year, higher than that from 2010 to 2014 about 0.4 percentage points per year. The peak age of the growth rate of myopia detection rate decreased from 12 years in 2010 to 10 years in 2014, and finally to 7 years in 2019. Conclusions: The detection rate of myopia among Chinese Han children and adolescents is still at a high level, and the peak age of the growth rate of myopia detection rate continues to advance.

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