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Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy:advances and perspectives

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Acta Pharmaceutica Sinica B 2020年第7期10卷 1253-1278页

作者： Yuan Fang Guochao Liao Bin Yu Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China International Institute for Translational Chinese MedicineGuangzhou University of Chinese MedicineGuangzhou 510006China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Blocking the MDM2/X-P53 protein-protein interaction has been widely recognized as an attractive therapeutic strategy for the treatment of cancers.Numerous small-molecule MDM2 inhibitors have been reported since the release of the structure of the MDM2-P53 interaction in 1996,SAR405838,NVP-CGM097,MK-8242,RG7112,RG7388,DS-3032 b,and AMG232 currently undergo clinical evaluation for cancer therapy.This review is intended to provide a comprehensive and updated overview of MDM2 inhibitors and proteolysis targeting chimera(PROTAC)degraders with a particular focus on how these inhibitors or degraders are identified from starting points,strategies employed,structure-activity relationship(SAR)studies,binding modes or co-crystal structures,biochemical data,mechanistic studies,and preclinical/clinical studies.Moreover,we briefly discuss the challenges of designing MDM2/X inhibitors for cancer therapy such as dual MDM2/X inhibition,acquired resistance and toxicity of P53 activation as well as future directions.

关键词： MDM2/X-P53 interaction MDM2/X inhibitors PROTAC degraders Cancer therapy

基于数据挖掘分析远方治疗慢性肾小球肾炎用药规律

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山西中医 2019年第5期35卷 46-49页

作者：毛锐远方辽宁中医药大学辽宁中医药大学附属医院

目的:采用数据挖掘技术对远方教授治疗慢性肾小球肾炎的用药规律进行分析。方法:收集远方教授治疗慢性肾小球肾炎门诊病例,应用SPSS Statistics 25.0、SPSS Modeler 18.0等统计软件分析处方用药规律。结果:共收集病例239例,中药197味,... 详细信息

目的:采用数据挖掘技术对远方教授治疗慢性肾小球肾炎的用药规律进行分析。方法:收集远方教授治疗慢性肾小球肾炎门诊病例,应用SPSS Statistics 25.0、SPSS Modeler 18.0等统计软件分析处方用药规律。结果:共收集病例239例,中药197味,以补虚、清热、收涩药为主,多用温、平、寒性药,多用甘、苦、辛味药,多用归属肝、脾、胃、肺、肾经的药物。得到常用药物组合4组、药对5对。结论:远方教授治疗慢性肾小球肾炎围绕"虚、热、瘀、湿"的病机核心,扶正祛邪并行,重视肝、脾、肺、肾的调理。

关键词：慢性肾小球肾炎数据挖掘聚类分析关联分析用药规律

Stressful life events,psychosocial health and general health in preschool children before age 4

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World Journal of Pediatrics 2023年第3期19卷 243-250页

作者： Jie Luo Amy van Grieken Shuang Zhou Yuan Fang Hein Raat Department of Public Health Erasmus MCDr.Molewaterplein 403015 GD RotterdamThe Netherlands Department of Maternal and Child Health School of Public HealthPeking UniversityBeijingChina

Background The impact of stressful life events(SLEs)in early childhood is often ignored.We aimed to examine longitudinal associations between SLEs and psychosocial and general health in preschool children.Methods Twelve SLEs occurring before the age of 24 months were assessed and categorized by frequency(no events,1-2 SLEs,and>2 SLEs)and overall tension(no events,low,and high)(n=1431).Psychosocial and general health were meas-ured three times at the age of 24,36 and 45 months.The associations were examined by logistic regression models using generalized estimating equations to handle repeated measurements.Results Half(48.4%)of the families experienced SLEs,and 23.8%perceived high-tension SLEs before the children were aged 24 months.Gender differences were observed in the association between SLEs and psychosocial health.Compared to girls without SLEs,girls who experienced>2 SLEs[OR=3.31,95%confidence interval(CI)2.05-5.35]or high-tension SLEs(OR=3.01,95%CI 2.07-4.39)had higher odds of psychosocial problems from 24 to 45 months.The odds ratios in boys were 2.10(95%CI 1.36-3.24)and 1.47(95%CI 1.06-2.03),respectively.Moreover,only girls'risk of psychosocial problems increased after experiencing 1-2 SLEs(OR=2.15,95%CI 1.54-3.00)or low-tension SLEs(OR=1.90,95%CI 1.31-2.74).Regarding general health,children who experienced>2 SLEs(OR=1.96,95%CI 1.21-3.18)and high-tension SLEs(OR=1.60,95%CI 1.12-2.28)had higher odds of poor general health from 24 to 45 months.Conclusions The findings emphasized that young children's psychosocial and general health can be impacted by experienc-ing SLEs in early childhood.Attention and adequate support for families experiencing SLEs are needed to minimize the potential negative effect of SLEs on child health,particularly in girls.

关键词： Child health Preschool children Stressful life event

Development and Validation of a Prediction Model on Adult Emergency Department Patients for Early Identification of Fulminant Myocarditis

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Current Medical Science 2023年第5期43卷 961-969页

作者： Min JIANG Jian KE Ming-hao fang Su-fang HUANG yuan-yuan LI Department of Emergency Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective It is difficult to predict fulminant myocarditis at an early stage in the emergency department.The objective of this study was to construct and validate a simple prediction model for the early identification of fulminant myocarditis.Methods A total of 61 patients with fulminant myocarditis and 160 patients with acute myocarditis were enrolled in the training and internal validation cohorts.LASSO regression and multivariate logistic regression were selected to develop the prediction model.The selection of the model was based on overall performance and simplicity.A nomogram based on the optimal model was built,and its clinical usefulness was evaluated by decision curve analysis.The predictive model was further validated in an external validation group.Results The resulting prediction model was based on 4 factors:systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality.The Brier scores of the final model were 0.078 in the training data set and 0.061 in the internal testing data set,respectively.The C-indexes of the training data set and the testing data set were 0.952 and 0.968,respectively.Decision curve analysis showed that the nomogram model developed based on the 4 predictors above had a positive net benefit for predicting probability thresholds.In the external validation cohort,the model also showed good performance(Brier score=0.007,and C-index=0.989).Conclusion We developed and validated an early prediction model consisting of 4 clinical factors(systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality)to identify potential fulminant myocarditis patients in the emergency department.

关键词： fulminant myocarditis emergency risk prediction nomogram

Modified min-sum SCAN decoding algorithm for polar codes

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The Journal of China Universities of Posts and Telecommunications 2018年第6期25卷 90-96页

作者： Yuan Fang Tian Bin State Key Laboratory of Integrated Services Networks Xidian UniversityXi'an 710071China Collaborative Innovation Center of Information Sensing and Understanding at Xidian University Xi'an 710071China China Electronics Technology Croup Corporation Key Laboratory of Aerospace Information Applications Shijiazhuang 050081China

The state-of-the-art soft-output decoder of polar codes is the soft cancellation(SCAN) decoding algorithm, which performs well at the cost of plentiful computations. Based on the SCAN decoding algorithm, a modified method with revised iterative formula is proposed, marked modified min-sum SCAN(MMS-SCAN). The proposed algorithm simplifies the update formula of nodes and reduces the complexity of iterative decoding process by the piecewise approximation function. Meanwhile, the bit error rate(BER) of the proposed method can approach the performance of original SCAN decoding method without performance loss. The simulation reveals that the MMS-SCAN decoding algorithm can achieve the effect that the BER curve almost coincides with the original SCAN decoding curve.

关键词： polar codes MMS-SCAN iterative formula the piecewise approximation function

Analysis on the development status of DNA storage based on papers and patents

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High Technology Letters 2021年第2期27卷 218-225页

作者：郑彦宁 Yuan Fang An Shudi Institute of Scientific and Technical Information of China Beijing 100038P.R.China

DNA storage as a disruptive technology is expected to solve the problem of massive data storage.Based on bibliometric analysis of DNA storage related papers and patents,this paper analyzes the development trend of DNA storage technology.The results show that DNA technology is still in the development stage,in which only a small number of researchers are involved.USA is the global leading country of DNA storage research.Both universities and companies in USA have played an important role in promoting DNA storage research.China is second only to USA in the number of DNA storage related papers or patents.However,in terms of patents layout,Chinese institutions don’t have sufficient intention of opening up the global market in the application of DNA storage.Although there have been several breakthrough advances in DNA storage,there are still many challenges to be solved.

关键词： DNA storage information digital data bibliometric analysis 0 Introduction

On Free Boundary Problem for the Non-Newtonian Shear Thickening Fluids

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Journal of Partial Differential Equations 2021年第1期34卷 14-41页

作者： WANG Shu Yuan Fang College of Applied Sciences Beijing University of TechnologyBeijing 100124China China Everbright Bank Beijing 100054China

The aim of this paper is to explore the free boundary problem for the NonNewtonian shear thickening fluids.These fluids not only have vacuum,but also have strong nonlinear properties.In this paper,a class of approximate solutions is first constructed,and some uniform estimates are obtained for these approximate solutions.Finally,the existence of free boundary problem solutions is proved by these uniform estimates.

关键词： On free boundary problem the non-Newtonian shear thickening fluids vacuum

Coastal mudflats as reservoirs of extracellular antibiotic resistance genes: Studies in Eastern China

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Journal of Environmental Sciences 2023年第7期129卷 58-68页

作者： Qingbin yuan Xiaolin Wang Hui fang yuan Cheng Ruonan Sun Yi Luo College of Environmental Science and Engineering Nanjing Tech UniversityNanjing 211816China State Key Laboratory of Pollution Control and Resource Reuse School of the EnvironmentNanjing UniversityNanjing 210023China School of Medicine Nankai UniversityTianjin 300071China Department of Civil and Environmental Engineering Rice UniversityHouston 77005USA

Despite coastal mudflats serving as essential ecological zones interconnecting terrestrial/freshwater and marine systems,little is known about the profiles of antibiotic resistance genes(ARGs)in this area.In this study,characteristics of typical ARGs,involving both intracellular(iARGs)and extracellular ARGs(eARGs)at different physical states,were explored in over 1000 km of coastal mudflats in Eastern China.Results indicated the presence of iARGs and eARGs at states of both freely present or attached by particles.The abundance of eARGs was significantly higher than that of iARGs(87.3%vs 12.7%),and their dominance was more significant than those in other habitats(52.7%-76.3%).ARG abundance,especially for eARGs,showed an increasing trend(p<0.05)from southern(Nantong)to northern(Lianyungang)coastalmudflats.Higher salinity facilitated the transformation from iARGs to eARGs,and smaller soil particle size was conducive to the persistence of eARGs in northern coastal mudflats.This study addresses the neglected function of coastal mudflats as eARGs reservoirs.

关键词： Antibiotic resistance genes(ARGs) Extracellular antibiotic resistance genes(eARGs) Coastal mudflats Amplicon sequencing Geochemical variable Mobile genetic elements

Effects of creep characteristics of natural gas hydrate-bearing sediments on wellbore stability

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Petroleum Science 2022年第1期19卷 220-233页

作者： Yang Li yuan-fang Cheng Chuan-Liang Yan Zhi-yuan Wang Li-fang Song School of Petroleum Engineering China University of Petroleum(East China)66 West Changjiang RoadHuangdao DistrictQingdao 266000China

Natural gas hydrate(NGH)reservoirs consist of the types of sediments with weak cementation,low strength,high plasticity,and high creep.Based on the kinetics and thermodynamic characteristics of NGH decomposition,herein a heat-fluid-solid coupling model was established for studying the wellbore stability in an NGH-bearing formation to analyze the effects of the creep characteristics of NGH-bearing sediments during long-term drilling.The results demonstrated that the creep characteristics of sediments resulted in larger plastic yield range,thus aggravating the plastic strain accumulation around the wellbore.Furthermore,the creep characteristics of NGH-bearing sediments could enhance the effects induced by the difference in horizontal in situ stress,as a result,the plastic strain in the formation around the wellbore increased nonlinearly with increasing difference in in situ stress.The lower the pore pressure,the greater the stress concentration effects and the higher the plastic strain at the wellbore.Moreover,the lower the initial NGH saturation,the greater the initial plastic strain and yield range and the higher the equivalent creep stress.The plastic strain at the wellbore increased nonlinearly with decreasing initial saturation.

关键词： Natural gas hydrates Wellbore stability Creep Plastic yield