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| 1 | China National Medical Products Administration approval summary:anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy显示文摘Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy. | Ming Zhou Xiaoyuan Chen Hong Zhang Lin Xia Xin Tong Limin Zou Ruimin Hao Jianhong Pan Xiao Zhao Dongmei Chen Yuanyuan Song Yueli Qi Ling Tang Zhifang Liu Rong Gao Yuankai Shi Zhimin Yang | 2019 | Cancer Communications2019，39，1： | 35 |
| 2 | 中国国家药品监督管理局批准安罗替尼用于经两种系统化疗后疾病进展的晚期非小细胞肺癌的治疗显示文摘背景2018年5月8日,中国国家药品监督管理局(National Medical Products Administration,NMPA)批准了小分子多靶点抗血管抑制剂盐酸安罗替尼,用于既往经过至少两种系统化疗后疾病进展的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的治疗。概要中国NMPA审查了一项随机双盲、安慰剂对照的III期临床试验,该临床试验的主要终点为总生存期(overall survival,OS)。试验共纳入437例患者随机分组(2∶1)接受安罗替尼(n=294)或安慰剂(n=143)治疗,每日1次,连服2周,停药1周。表皮生长因子受体(epidermal growth factor receptor,EGFR)基因敏感突变或间变性淋巴瘤激酶(activating anaplasticlymphomakinase,ALK)阳性的患者须经过NMPA已批准的药物治疗后出现疾病进展。安罗替尼为中国NMPA批准的用于治疗既往经过两种及以上系统化疗后疾病进展的晚期NSCLC患者的首个药物。安罗替尼组的中位OS(9.46个月)较安慰剂组[6.37个月;风险比(hazard ratio,HR)=0.70,95%置信区间(confidence Interval,CI):0.55–0.89;双侧log-rank P=0.002]显著延长。安罗替尼组的客观缓解率(objective responserate,ORR)为9.2%,安慰剂组为0.7%。安罗替尼组的中位缓解持续时间(durationofresponse,DoR)为4.83个月,95%CI为3.31–6.97个月。安罗替尼的常见不良反应(adverse drug reactions,ADRs)包括高血压(67.4%)、手足综合征(43.9%)、咳血(14.0%)、促甲状腺激素(thyroid stimulating hormone,TSH)升高(46.6%)、心电图QT间期(corrected QT Interval,QTc)延长(26.2%)。结论安罗替尼显著延长了患者的OS,可作为经二线及以上化疗后晚期或转移性非小细胞肺癌的一种新的治疗方案。 | Ming Zhou Xiaoyuan Chen Hong Zhang Lin Xia Xin Tong Limin Zou Ruimin Hao Jianhong Pan Xiao Zhao Dongmei Chen Yuanyuan Song Yueli Qi Ling Tang Zhifang Liu Rong Gao Yuankai Shi Zhimin Yang | 2019 | 癌症2019，38，12： | 7 |
| 3 | Spatiotemporal variations of nitrate sources and dynamics in a typical agricultural riverine system under monsoon climate显示文摘Nitrogen pollution is a serious environmental issue in the Danjiangkou Reservoir region(DRR),the water source of the South-to-North Water Diversion Project of China.In this research,seasonal surveys and a bi-weekly time series survey were conducted in the Qihe River Basin,one of the most densely populated agricultural basins in the DRR.Hydrochemical compositions(NO3^-Cl^-),dual isotopes(δD-H2O,δ^18O-H2O,δ^15N-NO3^-,andδ^18O-NO3^-),and a Markov Chain Monte Carlo isotope mixing model were jointly applied to unravel the sources,migrations,and transformations of the nitrate(NO3^-)in the basin.It was revealed that the mixing between different sources was the main process controlling the isotopic compositions of the riverine NO3the upper-middle reaches.In contrast,denitrification occurred in the lower reaches.For the first time,the sources of NO3^-quantified at a basin scale in the DRR.Overall,the river transported 484.2 tons/year of NO3^-N to the reservoir,of which 32.6%,36.4%,28.0%,and 3.0%was from soil organic nitrogen,chemical fertilizer,residential sewage and atmospheric precipitation,respectively.The NO3^-N fluxes of the different sources were regulated by the monsoon climate and anthropogenic activities.For example,high precipitation and intense fertilization resulted in severe nonpoint source pollution.Denitrification thrived in soils and reservoirs in wet seasons.Temperature could regulate the migration,nitrification and denitrification processes.Based on the results,we suggest that the management strategies dealing with nitrogen pollution issue in the DRR should follow the specific spatiotemporal characteristics of NO3migration and transformation mechanisms. | Hao Jiang Wenjing Liu Jiangyi Zhang Li Zhou Xiaode Zhou Ke Pan Tong Zhao Yuchen Wang Zhifang Xu | 2020 | Journal of Environmental Sciences2020，32，7： | 5 |
| 4 | Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype显示文摘Whether direct manipulation of Parkinson’s disease(PD)risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue.Here,we used an adeno-associated virus serotype 9(AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras(SNs)of two monkey groups:an old group and a middle-aged group.After the operation,the old group exhibited all the classic PD symptoms,including bradykinesia,tremor,and postural instability,accompanied by key pathological hallmarks of PD,such as severe nigral dopaminergic neuron loss(>64%)and evidentα-synuclein pathology in the gene-edited SN.In contrast,the phenotype of their middle-aged counterparts,which also showed clear PD symptoms and pathological hallmarks,were less severe.In addition to the higher final total PD scores and more severe pathological changes,the old group were also more susceptible to gene editing by showing a faster process of PD progression.These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys.Taken together,this system can effectively develop a large number of genetically-edited PD monkeys in a short time(6–10 months),and thus provides a practical transgenic monkey model for future PD studies. | Hao Li Shihao Wu Xia Ma Xiao Li Tianlin Cheng Zhifang Chen Jing Wu Longbao Lv Ling Li Liqi Xu Wenchao Wang Yingzhou Hu Haisong Jiang Yong Yin Zilong Qiu Xintian Hu | 2021 | Neuroscience Bulletin2021，37，9： | 2 |
| 5 | Transcellular distribution heterogeneity of Annexin A5 represents a protective response to lupus-related thrombophilia: A pilot Proteomics-based study显示文摘 | Di Zhou Na Luo Qiao Wu Yi You Zhifang Zhai Zhirong Mou Yuzhang Wu Fei Hao | 2012 | Biochemical and Biophysical Research Communications2012，，2： | 1 |
| 6 | Effect of roasting activation of rare earth molten salt slag on extraction of rare earth,lithium and fluorine显示文摘A new process was proposed to extract rare earth elements(REEs),Li and F from electrolytic slag of rare earth molten salt by synergistic roasting and acid leaching.Firstly,the thermodynamic analysis of roasting reaction was carried out,then the effects of roasting factors on leaching REEs,Li and F in slag were investigated.In additions,the mineral phase and morphology of molten salt slag,roasting slag and acid leaching slag were characterized,and the migration mechanism of REES,Li and F minerals in roasting and leaching process was analyzed.The results show that the synergistic roasting and activation of molten salt slag by CaO and Al_(2)(SO_(4))_(3)are thermodynamically feasible.The optimum roasting conditions are as follows:molten salt slag of 20 g,Al_(2)(SO_(4))_(3)of 31.25 g and CaO of 6.25 g,roasting temperature of 1173.15 K and reaction time of 2 h,under this condition,the leaching rates of Nd,Pr,Gd,Li and F are 92.47%,91.56%,91.08%,96.69%and 96.8%,respectively.X-ray powder diffraction(XRD)and scanning electron microscopy-energy dispersive X-ray spectroscopy(SEM-EDS)analysis show that the rare earth fluoride(REF3)in molten salt slag transforms into soluble rare earth oxide(REO)after roasting and activation.After leaching,the leaching residue is mainly strip CaSO4,indicating that REES,Li and F can be fully extracted from molten salt slag. | Zhifang Tong Xiaofei Hu Hao Wen | 2023 | Journal of Rare Earths2023，41，2： | 1 |
| 7 | Analysis of culture and drug sensitivity tests of Mycoplasmas for 387 patients with nongonococcal urethritis (cervicitis) in Chongqing显示文摘 | Zhai zhifang Hao Fei Zhong Baiyu | 2004 | Chin J Sex Transm Infect2004，4，2： | 1 |
| 8 | Approach for Predicting the Knowledge Points of Math Questions显示文摘In order to provide high-quality learning services,various online systems should possess the fundamental ability to predict the knowledge points and units to which a given test question belongs.The existing methods typically rely on manual labeling or traditional machine learning methods.Manual labeling methods have high time costs and high demands for human resources,while traditional machine learning methods only focus on the shallow features of the topics,ignoring the deep semantic relationship between the topic text and the knowledge point units.These two methods have relatively large limitations in practical applications.This paper proposes a convolutional neural network method combined with multiple features to predict the knowledge point units.We construct a binary classification dataset in the three grades of primary mathematics.Considering the supplementary role of Pinyin to Chinese text and the unique identification characteristics of Unicode encoding for characters,we obtain the Pinyin representation and the Unicode encoding representation of the original Chinese text.Then,we put the three representation methods into the convolutional neural network for training,obtain three kinds of semantic vectors,fuse them,and finally obtain higher-dimensional fusion features.Our experimental results demonstrate that our approach achieves good performance in predicting the knowledge units of test questions. | Kui Xiao Kong Huang Zhifang Huang Hao Chen | 2023 | 计算机教育2023，，12： | 0 |
| 9 | Scientific Advances and Weather Services of the China Meteorological Administration’s National Forecasting Systems during the Beijing 2022 Winter Olympics显示文摘Since the Beijing 2022 Winter Olympics was the first Winter Olympics in history held in continental winter monsoon climate conditions across complex terrain areas,there is a deficiency of relevant research,operational techniques,and experience.This made providing meteorological services for this event particularly challenging.The China Meteorological Administration(CMA)Earth System Modeling and Prediction Centre,achieved breakthroughs in research on short-and medium-term deterministic and ensemble numerical predictions.Several key technologies crucial for precise winter weather services during the Winter Olympics were developed.A comprehensive framework,known as the Operational System for High-Precision Weather Forecasting for the Winter Olympics,was established.Some of these advancements represent the highest level of capabilities currently available in China.The meteorological service provided to the Beijing 2022 Games also exceeded previous Winter Olympic Games in both variety and quality.This included achievements such as the“100-meter level,minute level”downscaled spatiotemporal resolution and forecasts spanning 1 to 15 days.Around 30 new technologies and over 60 kinds of products that align with the requirements of the Winter Olympics Organizing Committee were developed,and many of these techniques have since been integrated into the CMA’s operational national forecasting systems.These accomplishments were facilitated by a dedicated weather forecasting and research initiative,in conjunction with the preexisting real-time operational forecasting systems of the CMA.This program represents one of the five subprograms of the WMO’s high-impact weather forecasting demonstration project(SMART2022),and continues to play an important role in their Regional Association(RA)II Research Development Project(Hangzhou RDP).Therefore,the research accomplishments and meteorological service experiences from this program will be carried forward into forthcoming highimpact weather forecasting activities.This article provides an overview and assessment of this program and the operational national forecasting systems. | Guo DENG Xueshun SHEN Jun DU Jiandong GONG Hua TONG Liantang DENG Zhifang XU Jing CHEN Jian SUN Yong WANG Jiangkai HU Jianjie WANG Mingxuan CHEN Huiling YUAN Yutao ZHANG Hongqi LI Yuanzhe WANG Li GAO Li SHENG Da LI Li LI Hao WANG Ying ZHAO Yinglin LI Zhili LIU Wenhua GUO | 2024 | Advances in Atmospheric Sciences2024，41，5： | 0 |
| 10 | Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells显示文摘Macrophages are widely distributed immune cells that contribute to tissue homeostasis.Human THP-1 cells have been widely used in various macrophage-associated studies,especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes.However,the molecular characterization of four M2 subtypes(M2a,M2b,M2c,and M2d)derived from THP-1has not been fully investigated.In this study,we systematically analyzed the protein expression profiles of human THP-1-derived macrophages(M0,M1,M2a,M2b,M2c,and M2d)using quantitative proteomics approaches.The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated.The results showed that M2a and M2b,and M2c and M2d have very similar protein expression profiles.These data could serve as an important resource for studies of macrophages using THP-1 cells,and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research. | Pengfei LI Chen MA Jing LI Shanshan YOU Liuyi DANG Jingyu WU Zhifang HAO Jun LI Yuan ZHI Lin CHEN Shisheng SUN | 2022 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2022，23，5： | 0 |
| 11 | Application of StrucGP in medical immunology:site-specific N-glycoproteomic analysis of macrophages显示文摘The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals.Meanwhile,the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions.In this work,we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis.The intact glycopeptides of macrophages were enriched and analyzed using mass spectrometry(MS)-based glycoproteomic approaches,followed by the large-scale mapping of site-specific glycan structures via StrucGP.Results revealed that bisected GlcNAc,core fucosylated,and sialylated glycans(e.g.,HexNAc4Hex5Fuc1Neu5Ac1,N4H5F1S1)were increased in M1 and M2 macrophages,especially in the latter.The findings indicated that these structures may be closely related to macrophage polarization.In addition,a high level of glycosylated PD-L1 was observed in M1 macrophages,and the LacNAc moiety was detected at Asn-192 and Asn-200 of PD-L1,and Asn-200 contained Lewis epitopes.The precision structural interpretation of site-specific glycans and subsequent intervention of target glycoproteins and related glycosyltransferases are of great value for the development of new diagnostic and therapeutic approaches for different diseases. | Pengfei Li Zexuan Chen Shanshan You Yintai Xu Zhifang Hao Didi Liu Jiechen Shen Bojing Zhu Wei Dan Shisheng Sun | 2023 | Frontiers of Medicine2023，17，2： | 0 |
| 12 | Fast thermal responsive separators toward long-life and safe lithium metal batteries显示文摘Lithium metal batteries(LMBs)have been extensively investigated during the past decades because of their ultrahigh energy densities.With the increasing demand for energy density,however,the safety issue of LMBs has become a significant challenge.In particular,localized areas of increased temperature(namely,hotspots)may be induced and even exacerbated within LMBs by uneven current distribution,internal short circuits,or inadequate heat dissipation,which significantly sacrifices battery safety and cycle life.Here,we report the rational design and fabrication of a fast thermal responsive separator capable of inhibiting the growth of lithium dendrites and mitigating thermal propagation,thereby reducing the risk of thermal runaway.The as-achieved separator comprises both an electrospun membrane using a phase change material with superior thermal-storage ability and a thermally conductive modification layer of hexagonal boron nitride nanosheets with a fast heat-transfer feature.It is demonstrated that such a unique integration of heat conduction and heat storage enables the functional separator with attractive abilities to mitigate hotspots and inhibit the growth of lithium dendrites upon the cycling of LMBs.Moreover,pouch cells with the thermal-responsive separator,as well as numerical simulations,verify much enhanced safety and cycle life of LMBs.This work may offer a new conceptual design of intelligent separators that acts as a functional unit encapsulated within a single cell to boost in-situ thermal management,which will help to develop high-safety and energy-dense LMBs. | Pingan Li Zhifang Liu Yitong Peng Shanshan Yang Tao Meng Yunhuan Hu Yingjun Jiang Hao Sun Qi Li Xianluo Hu | 2024 | Nano Research2024，17，4： | 0 |
| 13 | P&T-Inf: A Result Inference Method for Context-Sensitive Tasks in Crowdsourcing显示文摘Context-Sensitive Task(CST)is a complex task type in crowdsourc-ing,such as handwriting recognition,route plan,and audio transcription.The current result inference algorithms can perform well in simple crowd-sourcing tasks,but cannot obtain high-quality inference results for CSTs.The conventional method to solve CSTs is to divide a CST into multiple independent simple subtasks for crowdsourcing,but this method ignores the context correlation among subtasks and reduces the quality of result inference.To solve this problem,we propose a result inference algorithm based on the Partially ordered set and Tree augmented naive Bayes Infer(P&T-Inf)for CSTs.Firstly,we screen the candidate results of context-sensitive tasks based on the partially ordered set.If there are parallel candidate sets,the conditional mutual information among subtasks containing context infor-mation in external knowledge(such as Google n-gram corpus,American Contemporary English corpus,etc.)will be calculated.Combined with the tree augmented naive(TAN)Bayes model,the maximum weighted spanning tree is used to model the dependencies among subtasks in each CST.We collect two crowdsourcing datasets of handwriting recognition tasks and audio transcription tasks from the real crowdsourcing platform.The experimental results show that our approach improves the quality of result inference in CSTs and reduces the time cost compared with the latest methods. | Zhifang Liao Hao Gu Shichao Zhang Ronghui Mo Yan Zhang | 2023 | Intelligent Automation & Soft Computing2023，，7： | 0 |
| 14 | The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1显示文摘Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains unclear.In this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy.Coimmunoprecipitation(Co-IP)/mass spectrometry(MS)was used to identify the potential mechanism.Through Co-IP,we detected and confirmed the main potential TNIK interactors.Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)fractions.We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls.NCB-0846 delayed kindling progression and decreased seizure severity.Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably CaMKIl.Co-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and GABRG2.In addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling.Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target. | Min Wang Yixue Gu Qiubo Li Bangzhe Feng Xinke Lv Hao Zhang Qingxia Kong Zhifang Dong Xin Tian Yanke Zhang | 2024 | Genes & Diseases2024，11，3： | 0 |
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