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.A new strategy for pharmacodynamic substance screening and research on gut microbiota pathway mechanisms based on UPLC-Q-orbitrap-MS and 16S rRNA
Zhiying Yu ; Tong Li ; Jie Yang ; Jianghua He ; Weijiang Zhang ; Siyuan Li ; Yunpeng Qi ; Yihui Yin ; Ling Dong ; Wenjuan Xu
Journal of Traditional Chinese Medical Sciences 2025;2025(1):56-70
Objective:
To establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota.
Methods:
The pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed.
Results:
We identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes.
Conclusion
This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.
3.Interpretation of presynaptic dopaminergic PET imaging results
Ping WU ; Jianjun WU ; Xun SUN ; Jingjie GE ; Fangyang JIAO ; Chengfeng JIANG ; Lirong JIN ; Xinlu WANG ; Zhenguang WANG ; Yafu YIN ; Ruixue CUI ; Rong TIAN ; Shuo HU ; Rongbing JIN ; Jianjun LIU ; Xiangsong ZHANG ; Ling CHEN ; Jie LU ; Xingmin HAN ; Yihui GUAN ; Xiaoli LAN ; Chuantao ZUO ; Jian WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(4):236-241
Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.
4.Guidance for operation and reading of 18F-FDG PET brain imaging in dementia
Huiwei ZHANG ; Jiaying LU ; Zhemin HUANG ; Ruixue CUI ; Xiaoli LAN ; Jie LU ; Xiangsong ZHANG ; Liping FU ; Yafu YIN ; Rongbing JIN ; Shicun WANG ; Jianjun WU ; Qianhua ZHAO ; Yihui GUAN ; Chuantao ZUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(10):613-618
Due to the availability of 18F-FDG in PET centers, this article aims to advocate and promote the standardization of 18F-FDG PET brain imaging in dementia in order to improve the reliability, repeatability and comparison of the imaging process and results. It is also provided to guide the PET imaging operation standard and to give suggestions on image interpretation.
5.Chinese neonatal birth weight curve for different gestational age.
Li ZHU ; Rong ZHANG ; Shulian ZHANG ; Wenjing SHI ; Weili YAN ; Xiaoli WANG ; Qin LYU ; Ling LIU ; Qin ZHOU ; Quanfang QIU ; Xiaoying LI ; Haiying HE ; Jimei WANG ; Ruichun LI ; Jiarong LU ; Zhaoqing YIN ; Ping SU ; Xinzhu LIN ; Fang GUO ; Hui ZHANG ; Shujun LI ; Hua XIN ; Yanqing HAN ; Hongyun WANG ; Dongmei CHEN ; Zhankui LI ; Huiqin WANG ; Yinping QIU ; Huayan LIU ; Jie YANG ; Xiaoli YANG ; Mingxia LI ; Wenjing LI ; Shuping HAN ; Bei CAO ; Bin YI ; Yihui ZHANG ; Chao CHEN ; null
Chinese Journal of Pediatrics 2015;53(2):97-103
OBJECTIVESince 1986, the reference of birth weight for gestational age has not been updated. The aim of this study was to set up Chinese neonatal network to investigate the current situation of birth weight in China, especially preterm birth weight, to develop the new reference for birth weight for gestational age and birth weight curve.
METHODA nationwide neonatology network was established in China. This survey was carried out in 63 hospitals of 23 provinces, municipalities and autonomous regions. We continuously collected the information of live births in participating hospitals during the study period of 2011-2014. Data describing birth weight and gestational age were collected prospectively. Newborn's birth weight was measured by electronic scale within 2 hours after birth when baby was undressed. The evaluation of gestational age was based on the combination of mother's last menstrual period, ultrasound in first trimester and gestational age estimation by gestational age scoring system.
STATISTICAL ANALYSISthe growth curve was drawn by using LMSP method, which was conducted in GAMLSS 1.9-4 software package in R software 2.11.1.
RESULTA total of 159 334 newborn infants were enrolled in this study. There were 84 447 male and 74 907 female. The mean birth weight was (3 232 ± 555) g, the mean birth weight of male newborn was (3 271 ± 576) g, the mean weight of female newborn was (3 188 ± 528) g. The test of the variables' distribution suggested that the distribution of gestational age and birth weight did not fit the normal distribution, the optimal distribution for them was BCT distribution. The Q-Q plot test and worm plot test suggested that this curve fitted the distribution optimally. The male and female neonatal birth weight curve was developed using the same method.
CONCLUSIONUsing GAMLSS method to establish nationwide neonatal birth weight curve, and the first time to update the birth weight reference in recent 28 years.
Birth Weight ; China ; Female ; Gestational Age ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Male
6.Self-rated health measurement scale in health check-up
Shouqing HUANG ; Lianhua YIN ; Yihui XU ; Liuxin WU
Chinese Journal of Health Management 2014;8(6):403-405
Objective To investigate the application value of the self-rated health measurement scale (SRHMS) in health check-up.Method A total of 8 083 health check-up receivers frow Fujian Province underwent SRHMS self-assessment,and the results of the assessment were analyzed by Chi-square test.Result The results of the survey showed that the total prevalence rate of chronic disease was 57.8% top five were stomach/duodenum diseases (14.57%),hypertension (11.58%),mammary gland disease (8.04%),abnormal blood lipid (7.16%) and prostate disease (6.54%).The proportion of these five kinds of illness was 43.38%.A positive correlation between the prevalence rate of chronic disease and age was found.The difference of the prevalence rate of chronic diseases between each age group was statistically significant (x2=863.816,P=0.000).Those with family history of chronic diseases accounted for 69.27% and those with history of present illness accounted for 57.83% (4 674/8 083).Bodily pain,dietary preferences,refined grain intake,lack of exercise,and alcohol drinking was found in 75.03%,60.15%,54.84%,46.07% and 41.50% participants.Conclusion The SRHMS could reflect the chronic disease incidence and unhealthy daily habits.
7.Discussions on basic medical insurance management for those seeing doctors out of hometown in China
Qiuxiao CHEN ; Yihui SUN ; Zhigang YAO ; Yin ZHANG ; Zhong JIANG
Chinese Journal of Hospital Administration 2013;(2):81-83
A consensus remains unsettled yet for basic medical insurance and common protocols on managing patients seeing doctors out of their hometown.This results in such setbacks as difficulty in seeing doctors elsewhere for those covered and in unaffordable financial burden,as well as medical insurance fraud,lack of information sharing among social insurance authorities,and difficulty of supervision.This study described the status quo of seeding doctors elsewhere under China's basic medical insurance system,and analyzed problems found in the management framework.On such basis,authors proposed such recommendations as unified management system for seeding doctors elsewhere,network information sharing for medical insurance information,and networked settlement for medical expenses for basic medical insurance.These measures should be carried out as per general requirements for health reform stage by stage.


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