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| 1 | An epigenomic approach to therapy for tamoxifen-resistant breast cancer显示文摘Tamoxifen 是为雌激素受体 alpha 的前线治疗(ERα) 在绝经前的女人的积极的胸肿瘤。然而,到 tamoxifen 的抵抗发生在许多病人。嗯仍然与获得的 tamoxifen 抵抗在乳癌房间的生长起一个关键作用,建议那 ERα为治疗仍然是一个有效目标 tamoxifen 抵抗(Tam-R ) 乳癌。以识别 ERα 的新奇管理者;发信号,通过对 histone 甲基修饰词的一幅小规模的 siRNA 屏幕,我们发现了 WHSC1, histone H3K36 methyltransferase, ERα 的一个积极管理者;在乳癌房间发信号。我们证明 WHSC1 被招募到 ERα由 BET 蛋白质 BRD3/4 的基因,并且便于 ERα基因表示。小分子的赌注蛋白质禁止者 JQ1 potently 压制了经典 ERα发信号的小径和在文化的 Tam-R 乳癌房间的生长。用一个 Tam-R 乳癌异种皮移植老鼠模型,我们与 JQ1 和 ER degrader fulvestrant 由 JQ1 和联合治疗的强壮的长持续的效果在 vivo 反胸癌症活动示威了。一起拿,我们提供 epigenomic 蛋白质 BRD3/4 和 WHSC1 是雌激素受体发信号的必要管理者并且是为 Tam-R 乳癌的治疗的新奇治疗学的目标的证据。 | Qin Feng Zheng Zhang Martin J Shea Chad J Creighton Cristian Coarfa Susan G Hilsenbeck Rainer Lanz Bin He Lei Wang Xiaoyong Fu Agostina Nardone Yongcheng Song James Bradner Nicholas Mitsiades Constantine S Mitsiades C Kent Osborne Rachel Schiff Bert W O'Malley | 2014 | Cell Research2014，24，7： | 10 |
| 2 | The C_(6)D_(6)detector system on the Back-n beam line of CSNS显示文摘Introduction The neutron capture cross sections are very important in the field of nuclear device design and basic physics research.Hydrogen-free liquid scintillator such as C_(6)D_(6)detectors are widely used in the neutron capture cross-sectional measurements for the low neutron sensitivity and fast time response.The Back-n white neutron source at China Spallation Neutron Source is the first spallation white neutron source in China,and it is suitable for neutron capture cross-sectional measurement.Materials and methods A C_(6)D_(6)detector system was built in the Back-n experimental station.The pulse height weighting technique was used to determine the system’s detection efficiency.The response to gamma rays of the C_(6)D_(6)detector was measured,and the energy resolution function was determined.Monte Carlo simulation with Geant4 code was carried out to get the weighting function of this C_(6)D_(6)detector system.Additionally,the systematic uncertainty of the weighting function was also determined.Conclusion According to the experimental and simulation results,this C_(6)D_(6)detector system can be used to measure neutron capture cross section. | Jie Ren Xichao Ruan Jie Bao Guangyuan Luan Wei Jiang Qi An Huaiyong Bai Ping Cao Qiping Chen Yonghao Chen Pinjing Cheng Zengqi Cui Ruirui Fan Changqing Feng Minhao Gu Fengqin Guo Changcai Han Zijie Han Guozhu He Yongcheng He Yuefeng He Hanxiong Huang Weiling Huang Xiru Huang Xiaolu Ji Xuyang Ji Haoyu Jiang Hantao Jing Ling Kang Mingtao Kang Bo Li Lun Li Qiang Li Xiao Li Yang Li Yang Li Rong Liu Shubin Liu Xingyan Liu Yinglin Ma Changjun Ning Binbin Qi Zhaohui Song Hong Sun Xiaoyang Sun Zhijia Sun Zhixin Tan Hongqing Tang Jingyu Tang Pengcheng Wang Qi Wang Taofeng Wang Yanfeng Wang Zhaohui Wang Zheng Wang Jie Wen Zhongwei Wen Qingbiao Wu Xiaoguang Wu Xuan Wu Likun Xie Yiwei Yang Han Yi Li Yu Tao Yu Yongji Yu Guohui Zhang Jing Zhang Linhao Zhang Liying Zhang Qingmin Zhang Qiwei Zhang Xianpeng Zhang Yuliang Zhang Zhiyong Zhang Yingtan Zhao Liang Zhou Zuying Zhou Danyang Zhu Kejun Zhu Peng Zhu | 2019 | Radiation Detection Technology and Methods2019，3，3： | 1 |
| 3 | The machine protection system for CSNS显示文摘Background The China Spallation Neutron Source(CSNS)accelerator consists of an 80 MeV H-LINAC,a 1.6 GeV rapid cycling synchrotron(RCS)and two beam transport lines.The uncontrolled beam may permanently damage the components or lead to very high residual radiation dose along the beam line.So the equipment protection must be deliberately designed and implemented.Purpose The machine protection system(MPS)protects components from being damaged by the beam.The response time requirement for the CSNS MPS is less than 20 ms,so the PLC(programmable logic controller)was adopted to implement the interlock logic.Methods The MPS was implemented as a two-tier architecture system,and developed through utilizing PLC and Experimental Physics and Industrial Control System(EPICS)software toolkits.The application logic was taken into careful consideration during the implementation stage.An embedded CPU module can function as an IOC accessing PLC I/O modules through the sequence CPU,with an embedded Linux operation system.Results The interlock logic and heartbeat functions were tested with all functions ok.Time consumption has been measured thoroughly since the important requirement,which is around 15 ms to stop the beam.Conclusions MPS was completed in Sep.2017 and then put into operation.It has been operating smoothly for more than 3 years.MPS has played an important role in every stage of CSNS’s commissioning and operation and achieved high reliability during the user’s experiment operation.The accelerator recently runs stably with low equipment failure. | Kang Mingtao Zhang Yuliang Jin Dapeng He Yongcheng Zhan Mingchuan Zhu Peng Wu Xuan Guo Fengqin Wang Lin | 2021 | Radiation Detection Technology and Methods2021，5，2： | 1 |
| 4 | A Norsesquiterpene Lactone and a Benzoic Acid Derivative from the Leaves of Cyclocarya paliurus and their Glucosidase and Glycogen Phosphorylase Inhibiting Activities显示文摘 | Jun Li Yuanyuan Lu Xiaojian Su Fu Li Zhigang She Xingcun He Yongcheng Lin | 2008 | Planta Med2008，，： | 1 |
| 5 | Prevalence and related factors of the absence of anemia among Chinese chronic hemodialysis patients: a multicenter cross-sectional study显示文摘 | WAN Qijun HE Yongcheng ZHANG Wanfan | 2014 | International urology and nephrology2014，46，8： | 1 |
| 6 | Turning a hot spot into a cold spot:polarization-controlled Fano-shaped local-field responses probed by a quantum dot显示文摘Optical nanoantennas can convert propagating light to local fields.The local-field responses can be engineered to exhibit nontrivial features in spatial,spectral and temporal domains,where local-field interferences play a key role.Here,we design nearly fully controllable local-field interferences in the nanogap of a nanoantenna,and experimentally demonstrate that in the nanogap,the spectral dispersion of the local-field response can exhibit tuneable Fano lineshapes with nearly vanishing Fano dips.A single quantum dot is precisely positioned in the nanogap to probe the spectral dispersions of the local-field responses.By controlling the excitation polarization,the asymmetry parameter q of the probed Fano lineshapes can be tuned from negative to positive values,and correspondingly,the Fano dips can be tuned across a broad spectral range.Notably,at the Fano dips,the local-field intensity is strongly suppressed by up to ~50-fold,implying that the hot spot in the nanogap can be turned into a cold spot.The results may inspire diverse designs of local-field responses with novel spatial distributions,spectral dispersions and temporal dynamics,and expand the available toolbox for nanoscopy,spectroscopy,nano-optical quantum control and nanolithography. | Juan Xia Jianwei Tang Fanglin Bao Yongcheng Sun Maodong Fang Guanjun Cao Julian Evans Sailing He | 2020 | Light(Science & Applications)2020，9，1： | 1 |
| 7 | Detector development at the Back-n white neutron source显示文摘Purpose Back-n is a white neutron beamline at China spallation neutron source,which was established in the year of 2018.It is a powerful facility for nuclear data measurement,neutron detector calibration,and radiation effect research.Method A series of detectors were built for different experiments,including beam monitoring,beam profile measurement,neutron induced secondaries(fission fragments,light charged particles and gamma)cross section measurement,and neutron resonance radiography,etc.A common digitization electronics and a cluster-based DAQ were developed for these detector systems.Most detectors have been employed at Back-n and serviced for experiments from the beginning of the beamline running.Results and conclusion As an overview of detectors of Back-n,the details of the detector design and the experiment performing are described in this paper.Some developing systems,e.g.,MTPC and B-MCP,are also included. | Fan Ruirui Li Qiang Bao Jie Li Yang Liu Rong Jiang Wei Ren Jie Zhang Qiwei Cao Ping Gu Minhao Ren Zhizhou Yi Han Tang Jingyu An Qi Bai Haofan Bai Jiangbo Chen Qiping Chen Yonghao Chen Zhen Cui Zengqi Fan Anchuan Feng Changqing Feng Fanzhen Gao Keqing Han Changcai Han Zijie He Guozhu He Yongcheng Hong Yang Hu Yiwei Huang Hanxiong Jia Weihua Jiang Haoyu Jiang Zhijie Jin Zhengyao Kang Ling Li Bo Li Chao Li Gong Li Jiawen Li Xiao Liu Jie Liu Shubin Luan Guangyuan Ning Changjun Qi Binbin Ruan Xichao Song Zhaohui Sun Kang Tan Zhixin Tang Shengda Wang Pengcheng Wang Zhaohui Wen Zhongwei Wu Xiaoguang Wu Xuan Xie Likun Yang Yiwei Yu Yongji Zhang Guohui Zhang Linhao Zhang Mohan Zhang Xianpeng Zhang Yuliang Zhang Yue Zhang Zhiyong Zhao Maoyuan Zhou Luping Zhou Zhihao Zhu Kejun The CSNS Back-n Collaboration | 2023 | Radiation Detection Technology and Methods2023，7，2： | 0 |
| 8 | Design and implementation of feedback logic of FOFB for HEPS显示文摘Purpose As a fourth-generation light source,High Energy Photon Source(HEPS)has much more stringent requirements to the beam orbit stability in both horizontal and vertical directions than the previous sources due to the much smaller beam sizes.Methods A Fast Orbit FeedBack(FOFB)system,with the closed-loop bandwidth around 500 Hz,is needed to meet the critical requirements.The latency of the FOFB system is the key to achieve these requirements.Results Proper design and implementation of the feedback logic to have low latency is illustrated in the paper.Calculation accuracy is kept in the whole operation except for the last-minute data translation into 32-bit floating point number. | Daoyuan Wang Dapeng Jin Peng Zhu Zhexin Xie Lei Zeng Yuliang Zhang Yongcheng He | 2023 | Radiation Detection Technology and Methods2023，7，3： | 0 |
| 9 | Correlation analysis of intestinal flora and pathological process of type 2 diabetes mellitus显示文摘Objective: To observe the relationship between the different stages of type 2 diabetes mellitus(T2DM)and the intestinal flora and verify its underlying mechanism.Methods: T2DM rats were generated by high-fat diet(HFD) combined with intraperitoneal streptozotocin(STZ) injection. The rats were divided into four groups: the control group(fed with normal feed for1 month), the HFD group(fed with HFD for 1 month), the T2DM group(HFD combined with STZ and blood glucose ≥11.1 m M), and the unformed T2DM model(Un-mod) group(HFD combined with STZ and blood glucose <11.1 m M). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S r RNA gene sequencing. The content of short-chain fatty acids(SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41(GPR41) and GPR43.Results: At different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased(all P <.05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group(both P <.001).Conclusion: The intestinal flora-SCFAs-GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values. | Yongcheng An Yuhui Duan Hongyu Dai Chen Wang Lu Shi Changhao He Yinglan Lv Huimin Li Shuhang Dai Baosheng Zhao | 2022 | Journal of Traditional Chinese Medical Sciences2022，9，2： | 0 |
| 10 | Metabolomics characterization of Qingwei San on oral ulcer in db/db mice with stomach heat pattern显示文摘Objective:To characterize the effects of Qingwei San(QWS)on diabetic oral ulcer(OU)mice with stomach heat pattern through metabolomic analysis.Methods:A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db(db/db)mice with dried Zingiber officinale Rosc.rhizome(Z.officinale,Gan Jiang)decoction by gavage.All model mice had blood glucose levels of≥11.1 m M.Subsequently,OU was induced by Na OH cauterization.After 1 week of administration of QWS,non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS).Results:The non-targeted metabolomics results indicated that tryptophan metabolism,2-oxocarboxylic acid metabolism,serotonergic synapses,amino sugar and nucleotide sugar metabolism,and amino acid biosynthesis were involved in the therapeutic effects of QWS,with tryptophan metabolism playing a predominant role.Conclusion:QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern.QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway. | Huimin Li Chen Wang Yinglan Lyu Lu Shi Changhao He Yongcheng An Huilin Zhang Hongbin Zhao Yonghua Zhao Baosheng Zhao | 2023 | Journal of Traditional Chinese Medical Sciences2023，10，3： | 0 |
| 11 | Cleavable bimetallic-organic polymers for ROS mediated cascaded cancer therapy under the guidance of MRI through tumor hypoxia relief strategy显示文摘Despite recent advances in tumor treatment, reactive oxygen species(ROS)-mediated therapy, such as photodynamic therapy(PDT) and chemical dynamic therapy(CDT), remains challenging mainly due to hypoxia in tumor microenviroment. Relieving the hypoxia of tumor tissue has been considered as an attractive strategy for enhancing efficacy of ROS-based cancer treatment.Herein, one cascaded platform was developed to overcome tumor hypoxia and synergistically enhance the effect of ROSmediated therapy. This platform is based on cleavable bimetallic metal organic polymers(DOX@Fe/Mn-THPPTK-PEG). As an efficient Fenton-like material, it could not only produce cytotoxic ·OH by catalyzing the decomposition of intracellular H2O2, but also generate O2 to alleviate tumor hypoxia. In addition, the DOX-loaded metal organic polymers(MOPs could be disrupted after being exposed to laser irradiation or/and treated with H2O2, and then release the DOX for chemotherapy. Overall, 3 therapies(hypoxia-relieved PDT, photo-enhanced CDT, and ROS-mediated chemotherapy) could be achieved simultaneously by such a smart platform. Furthermore, T1-weighted MRI imaging ability of the MOPs could be greatly improved under H2O2 treatment.Therefore, total four robust functions were realized in a simple platform. These findings demonstrate great clinical potentials of the MOPs for cancer theranostics. | Haozhe He Lihua Du Min Tan Yali Chen Liejing Lu Yongcheng An Yong Wang Xiaoxia Li Bo Li Jun Shen Jun Wu Xintao Shuai | 2020 | Science China Chemistry2020，63，7： | 0 |
| 12 | The run management system for CSNS显示文摘Purpose In order to increase CSNS beam power from 100 to 500 kW,the linac injection energy needs to be increased from 80 to 300 MeV.The combined layout of superconducting spoke cavities and elliptical cavities will be adopted to accelerate H−beam to 300 MeV.In this paper,a compact single spoke cavity withΦ50-mm beam aperture was proposed,with the RF performance of the spoke cavity optimized to Ep/Eacc<5,Bp/Eacc<9,as well as the good multipacting behavior.Methods CST Microwave Studio was used to optimize the RF performance(Epeak/Eacc,Bpeak/Eacc,R/Q)with cavity geometry parameters.After electromagnetic design was finished,multipacting behavior was studied with CST Particle Studio module,and cavity shape modification was made to get a reasonablevalue.Results The simulation got optimum results of Epeak/Eacc=4.97 and Bpeak/Eacc=8.42 mT/(MV/m),and themax is 1.52 at Eacc=7.74 MV/m.Conclusion A 648 MHzβg=0.4 single spoke cavity with beam apertureΦ50 mm was proposed in the paper.This compact cavity may be a very promising option for CSNS linac upgrading.In addition to the optimization of the RF parameters,the multipacting behavior of the cavity is also studied,and cavity shape is optimized to reducevalue. | Yuliang Zhang Mingtao Kang Dapeng Jin Yongcheng He Peng Zhu Xuan Wu Fengqin Guo Lin Wang Wenchun Gao Gang Li | 2019 | Radiation Detection Technology and Methods2019，3，3： | 0 |
| 13 | Clinical Application of PES Membrane Dialyzer显示文摘Objective The dialysate membrane can be classified into acetate membrane and synthetic membrane,while the latter can be further divided into polysulfone,polyacrylonitrile,etc.Polyethersulfone membrane is high molecular membrane material with excellent biocompatibility,stable mechanical properties,high temperature and pressure resistance,and good cleaning performance,which has been applied for more than 10 years.This trial is to assess the safety and efficacy of hollow polysulfone membrane fiber dialyzer with pattern number Enttex^(TM)-16LF(E60)for hemodialysis in patients with acute or chronic renal failure due to multiple factors.Methods Totally 76 patients receiving maintenance hemodialysis were included in a two-site,random,open label,two-stage,positive crossover and non inferiority validation study.The clinical efficacy and safety of the test device were observed,which was a hollow fiber dialyzer produced by Guangzhou Enttex Medical Products Co.,Ltd.,with polyethersulfone membrane imported from Germany.It was a low flux dialyzer with the pattern number of EnttexTM-16LF(E60).Inclusion criteria:①patients with acute or chronic renal failure due to various reasons who needed hemodialysis;②18 to 80 years old,gender unlimited;③patients who received stable dialysis for more than 3 months,regular hemodialysis 3 times a week,4 h at each time,blood flow rate of 200~350ml/min;④using bicarbonate dialysate at a flow rate of 500ml/min;⑤patients with arteriovenous fistula or who received artificial blood vessel puncture dialysis;received anticoagulation by heparin or low molecular weight heparin.Exclusion criteria:①patients needing heparin free dialysis for severe anemia,tumor and active bleeding;②patients with severe cardiac(gradeⅢcardiac function),hepatic(severe hepatitis and cirrhosis)and pulmonary diseases(severe respiratory failure).Results Comparison of parameters,including the changes of Kt/V,general creatinine and urea clearance rates and URR(urea reduction rate)shows no statistical significance in differences between the two devices,indicating that the test and control devices can equally and effectively eliminate toxins including creatinine and urea,etc.PPP and MITTP results are consistent.Comparison of ultrafiltration rates between two groups of patients shows no statistical difference.PPP and MITTP results are consistent,indicating that both the test device and control device can effectively eliminate water.In MITTP,electrolytes including K^+,Na^+,Cl^-,Ca^2+,HCO3^-,etc.show no statistical significance in difference between the test and control devices before and after dialysis(P>0.05).After treating by using test and control devices,body weight,serum potassium and phos-phorus all significantly decrease(P<0.001);serum Ca^2+,PO2,PCO2and HCO3^-all significantly increase(P<0.001).These results indicate that both the test and control devices can effectively eliminate serum potassium and phosphorus,and eliminate excess water in body,maintain the balance between liquid and electrolytes in patients.PPP and MITTP results are consistent.Conclusion This clinical trial confirms that hollow polyethersulfone membrane fiber dialyzer can be safely and effectively used in hemodialysis therapy. | YUN Chen YANG Peidian LIANG Wenxue CHEN Yu CHEN Gangyi LIU Hongping OUYANG Zihua SONG Huifeng LI Yunyi YU Zongchao GUAN Baozhang DONG Xiangnan LIU Huanhuan Cao Rui ZHANG Zeyu FAN Lijing HU Bo HE Yongcheng SHI Mingjie XU Jun Yang Lifeng TANG Shuifu | 2019 | 临床医学工程2019，26，S01： | 0 |
| 14 | Wearable ultrasensitive and rapid human physiological monitoring based on microfiber Sagnac interferometer显示文摘High-sensitive and fast-responding flexible strain sensors are essential for the smart wearable devices that precisely and dynamically perceive the weak deformations induced by human physiological signals.Here,a flexible strain sensor via polydimethylsiloxane(PDMS)-encapsulated microfiber Sagnac interferometer was designed and prepared for monitoring the human pulse signals and sound vibrations.The sensor achieved a record-breaking sensitivity(gauge factor,GF=9977)and an extremely low detection limit(0.00025%)due to the strong polarization-dependent coupling effect in the microfiber coupler and the polarization-mixing effect in the Sagnac loop.The relative intensity demodulation method also enabled a fast response time of 10μs.The wearable pulse measurements were implemented by attaching this flexible strain sensor directly to human skin at various locations and the waveform details were accurately captured.Taking advantage of the ultra-high sensitivity and fast response performance of the prepared sensor,the real-time dynamic acquisition of the underwater weak signal,such as the hydro-acoustic waves with a wide range of 20 Hz–16.86 k Hz,has been demonstrated.These initial results pave the way for a new and innovative category of underwater wearable devices with rapid detection of human physiological signals and weak environmental vibrations. | Xin WANG Hongyou ZHOU Meihua CHEN Yongcheng HE Zhishen ZHANG Jiulin GAN Zhongmin YANG | 2024 | Science China(Information Sciences)2024，67，3： | 0 |
| 15 | Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway显示文摘Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF’s anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D. | CHENG Long SHI Lu HE Changhao WANG Chen LV Yinglan LI Huimin AN Yongcheng DUAN Yuhui DAI Hongyu ZHANG Huilin HUANG Yan FU Wanxin SUN Weiguang ZHAO Baosheng | 2023 | Chinese Journal of Natural Medicines2023，21，11： | 0 |
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