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.Discovery of toad-derived peptide analogue targeting ARF6 to induce immunogenic cell death for immunotherapy of hepatocellular carcinoma.
Dihui XU ; Xiang LV ; Meng YU ; Ao TAN ; Jiaojiao WANG ; Xinyi TANG ; Mengyuan LI ; Wenyuan WU ; Yuyu ZHU ; Jing ZHOU ; Hongyue MA
Journal of Pharmaceutical Analysis 2025;15(3):101038-101038
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3.Research progress on natural products regulating osteogenic differentiation
Hu CAI ; Xiaoqian WU ; Lingfei HAN ; Feng FENG ; Wei QU ; Wenyuan LIU
Journal of China Pharmaceutical University 2025;56(1):10-21
As the important source of bone cells, osteoblasts are involved in bone formation and repair, and play a key role in maintaining bone balance. If the osteogenic differentiation process in vivo is disrupted, a variety of bone-related diseases may occur. Natural products, which have a wide range of sources, a wide variety of physiological activities, and few toxic side-effects, have been found in recent years to be able to regulate osteoblast differentiation. Based on the sources of natural products, this paper reviews the intervention of natural products from plant, animal and microbial sources on osteogenic differentiation, aiming to provide a theoretical basis for natural products in the treatment of bone diseases.
4.Standardized specialist training for developmental and behavioral pediatrics in China and the United States: current status and thoughts
Xiaoyang CHEN ; Lingling WU ; Wenhao LI ; Wenyuan JIN ; Yanyan WANG ; Xiaolin LIU ; Zhiwei ZHU
Chinese Journal of Medical Education Research 2024;23(3):314-320
The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.
5.Discussion on the pathogenesis and treatment of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation"
Mingyao XU ; Wenyuan SU ; Jing WU ; Jiawen HE ; Haowei ZHANG ; Jinjuan LI ; Jia YUE ; Yan ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(12):1745-1752
Non-alcoholic fatty liver disease is a common chronic liver disease in clinical practice. In recent years, with increasing social attention to the health of women and the elderly, the prevention and treatment of non-alcoholic fatty liver disease after menopause has increasingly become a research hotspot in metabolic diseases. This study explores the pathogenesis and treatment method of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation" and combined with the physiological and pathological characteristics of postmenopausal women and the Western medicine understanding of non-alcoholic fatty liver disease. We believe that the pathogenesis of non-alcoholic fatty liver disease in postmenopausal women is rooted in the "deficient qi" caused by depletion of liver and kidney essence and blood. The imbalance between the physical and functional aspects of the liver due to this "deficient qi" is the primary factor, while the "stagnation" of phlegm and blood stasis is the manifestation. Furthermore, the "deficient qi" and "stagnation" reinforce each other, with the deficiency leading to stagnation and stagnation exacerbating the deficiency, thus accelerating the progression of the disease. The treatment approach should be one that combines nourishing deficiency and resolving stagnation, addressing both root cause and maifestations. Given the female characteristic of "the liver as the innate organ" and the post-menopausal physiological state of "gradual decline of kidney essence", it is important to focus on nourishing the liver and kidneys, nurturing the liver′s physical body while maintaining its function, and also promoting the circulation of qi, resolving phlegm, and invigorating blood circulation to remove blood stasis. This approach aims to reduce the accumulation of lipids in the liver, offering a new perspective and approach for the treatment of non-alcoholic fatty liver disease in post-menopausal women with traditional Chinese medicine.
6.Interpretation of Chinese guideline for the prevention and treatment of anxiety disorders (the second edition)
Shenxun SHI ; Ning ZHANG ; Tianmei SI ; Zheng LU ; Jiyang PAN ; Xiufeng XU ; Wenyuan WU
Chinese Journal of Psychiatry 2024;57(6):327-336
The second edition of the Chinese guideline for the prevention and treatment of anxiety disorders was published in August 2023, 13 years after the first edition. The revision principles for the second edition were maintaining the first edition's framework, and based on that framework, making necessary revisions by incorporating research progress and supplementing the latest research findings from the domestic studies and the overseas literature. Referring to the DSM-5 and ICD-11 classifications of mental disorders and the actual clinical situation in China, the anxiety disorders in the second edition were panic disorder, generalized anxiety disorder, social anxiety disorder, separation anxiety disorder, and anxiety disorder due to another medical condition. The latest epidemiological data on anxiety disorders in China were added. Following the international guidelines, medications not included in the first edition have been added. Chinese traditional medicines, physical therapy, and internet web-based psychotherapy were also supplemented to fit Chinese clinical settings. Based on a literature review, the latest information on the risks of using antidepressants during pregnancy has been added.A whole course of treatment across the acute phase, consolidation phase, and maintenance phase was further addressed as the treatment principle. First-line and second-line recommendations are provided for medication selections.
7.Research progress in roles of AGE-RAGE axis in occurrence and development of metabolism-related diseases and its intervention
Cuimei ZHAO ; Yajing WU ; Yingran LI ; Xiuzhen LONG ; Xun ZHOU ; Wenyuan ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(12):952-958
Metabolism-related diseases are chronic diseases caused by genetic and environmental factors.The symptoms include insulin resistance,abnormal blood glucose and lipid levels,and elevated blood pressure.This type of illness has become a major threat to human health,and there is an urgent need to find effective treatments.Advanced glycation end products (AGE) are a group of complex and heterogeneous compounds that result from reduced interactions between the carbonyl groups of sugar and the free amino groups of proteins,lipids,and nucleic acids.Increasing evidence shows that AGE and its receptor (RAGE) are involved in the occurrence and development of such metabolism-related diseases as hypertension,diabetes,and atherosclerosis.AGE can have adverse effects on tissues through non-receptor and receptor-mediated mechanisms.In the receptor-mediated mechanism,AGE interacts with RAGE to increase the production of oxygen free radicals and activate NF-κB so that more pro-inflammatory cells are expressed and released,leading to cell damage.This article reviews the research progress in interventions with AGE and RAGE in the treatment of hypertension,diabetes,and atherosclerosis from a metabolic perspective in the hope of exploring the potential of AGE and RAGE as therapeutic targets for metabolism-related diseases.
8.Research progress in roles of AGE-RAGE axis in occurrence and development of metabolism-related diseases and its intervention
Cuimei ZHAO ; Yajing WU ; Yingran LI ; Xiuzhen LONG ; Xun ZHOU ; Wenyuan ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(12):952-958
Metabolism-related diseases are chronic diseases caused by genetic and environmental factors.The symptoms include insulin resistance,abnormal blood glucose and lipid levels,and elevated blood pressure.This type of illness has become a major threat to human health,and there is an urgent need to find effective treatments.Advanced glycation end products (AGE) are a group of complex and heterogeneous compounds that result from reduced interactions between the carbonyl groups of sugar and the free amino groups of proteins,lipids,and nucleic acids.Increasing evidence shows that AGE and its receptor (RAGE) are involved in the occurrence and development of such metabolism-related diseases as hypertension,diabetes,and atherosclerosis.AGE can have adverse effects on tissues through non-receptor and receptor-mediated mechanisms.In the receptor-mediated mechanism,AGE interacts with RAGE to increase the production of oxygen free radicals and activate NF-κB so that more pro-inflammatory cells are expressed and released,leading to cell damage.This article reviews the research progress in interventions with AGE and RAGE in the treatment of hypertension,diabetes,and atherosclerosis from a metabolic perspective in the hope of exploring the potential of AGE and RAGE as therapeutic targets for metabolism-related diseases.
9.Interpretation of Chinese guideline for the prevention and treatment of anxiety disorders (the second edition)
Shenxun SHI ; Ning ZHANG ; Tianmei SI ; Zheng LU ; Jiyang PAN ; Xiufeng XU ; Wenyuan WU
Chinese Journal of Psychiatry 2024;57(6):327-336
The second edition of the Chinese guideline for the prevention and treatment of anxiety disorders was published in August 2023, 13 years after the first edition. The revision principles for the second edition were maintaining the first edition's framework, and based on that framework, making necessary revisions by incorporating research progress and supplementing the latest research findings from the domestic studies and the overseas literature. Referring to the DSM-5 and ICD-11 classifications of mental disorders and the actual clinical situation in China, the anxiety disorders in the second edition were panic disorder, generalized anxiety disorder, social anxiety disorder, separation anxiety disorder, and anxiety disorder due to another medical condition. The latest epidemiological data on anxiety disorders in China were added. Following the international guidelines, medications not included in the first edition have been added. Chinese traditional medicines, physical therapy, and internet web-based psychotherapy were also supplemented to fit Chinese clinical settings. Based on a literature review, the latest information on the risks of using antidepressants during pregnancy has been added.A whole course of treatment across the acute phase, consolidation phase, and maintenance phase was further addressed as the treatment principle. First-line and second-line recommendations are provided for medication selections.
10.Constructing a Syndrome Differentiation Model by Combining Latent Structure Analysis of Association Rules: An Example of Kidney Yang Deficiency Syndrome in Primary Osteoporosis
Beibei LI ; Jing WANG ; Xinghua XIANG ; Wenyuan XU ; Weiguo BAI ; Mengyu LIU ; Yukun LI ; Xiaokun WU ; Yongjun WANG ; Wei YANG
Journal of Traditional Chinese Medicine 2023;64(24):2522-2531
ObjectiveTo construct a quantitative differentiation model of traditional Chinese medicine (TCM) syndromes by taking primary osteoporosis (POP) with kidney yang deficiency syndrome as an example, and to provide methodological reference for the standardization of syndrome differentiation. MethodsHigh-frequency clinical features of POP were screened by descriptive statistical analysis, and strong association features of POP were obtained by association rule algorithm. On this basis, a latent structure (latent tree) model was established through latent structure analysis, and the implicit and explicit variables (features) related to POP with kidney yang deficiency syndrome were comprehensively clustered, and the clustering results were interpreted by the indexes of mutual information and cumulative information coverage, to explore the primary and secondary symptoms, and to deduce the categories of POP with kidney yang deficiency syndrome based on the probability of the features appearing in the various latent categories. Based on the categories, the clinical feature scores and identification thresholds were calculated, and the syndrome differentiation model of POP with kidney yang deficiency was initially constructed by combining the comprehensive judgment rules. Finally, the results of TCM professionals' judgment were used as the gold standard to further evaluate the effectiveness of the model in assisting the syndrome differentiation. ResultsThe 32 features strongly associated with POP were obtained, and the Bayes information critedon score of the further constructed latent tree model was -15291.93. Based on the mutual information and the cumulative information coverage, the main symptoms of POP with kidney yang deficiency syndrome were bone weakness, fatigue, pale tongue, clear urine, frequent nocturnal urination, cold limbs, thin pulse, white coating, and secondary symptoms were weakness, loss of libido, loose stool, frequent urination, lumbar and knee weakness, and fear of cold. From the probability of the occurrence of each clinical feature in different latent categories of POP with kidney yang deficiency syndrome, the state was introduced as S0 category (none/mild kidney yang syndrome)/ S1 category (moderate kidney yang syndrome)/ S2 category (severe kidney yang syndrome). Optimizing the preliminary rules of state identification and refining the state of S1 category, the results showed that among 970 patients with POP, there were 520 patients having no/mild kidney yang deficiency syndrome, 224 patients with moderate to mild kidney yang deficiency syndrome, 81 patients with moderate to severe kidney yang deficiency syndrome, and 145 patients with severe kidney yang deficiency syndrome. During the evaluation and validation process, the correct rate of the model assessment index was 0.8835, while the sensitivity was 0.7181, and the specificity was 0.9437. ConclusionCombined with the latent structure analysis of the association rule, the syndrome differentiation model for POP with kidney yang deficiency could be constructed, and the model shows a good quantitative identification effect, which can provide methodological supports for clinicians to improve the efficiency and accuracy of TCM diagnosis.


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