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| 1 | Minimal invasive microscopic tooth preparation in esthetic restoration: a specialist consensus显示文摘By removing a part of the structure,the tooth preparation provides restorative space,bonding surface,and finish line for various restorations on abutment.Preparation technique plays critical role in achieving the optimal result of tooth preparation.With successful application of microscope in endodontics for>30 years,there is a full expectation of microscopic dentistry.However,as relatively little progress has been made in the application of microscopic dentistry in prosthodontics,the following assumptions have been proposed:Is it suitable to choose the tooth preparation technique under the naked eye in the microscopic vision?Is there a more accurate preparation technology intended for the microscope?To obtain long-term stable therapeutic effects,is it much easier to achieve maximum tooth preservation and retinal protection and maintain periodontal tissue and oral function health under microscopic vision?Whether the microscopic prosthodontics is a gimmick or a breakthrough in obtaining an ideal tooth preparation should be resolved in microscopic tooth preparation.This article attempts to illustrate the concept,core elements,and indications of microscopic minimally invasive tooth preparation,physiological basis of dental pulp,periodontium and functions involved in tool preparation,position ergonomics and visual basis for dentists,comparison of tooth preparation by naked eyes and a microscope,and comparison of different designs of microscopic minimally invasive tooth preparation techniques.Furthermore,a clinical protocol for microscopic minimally invasive tooth preparation based on target restorative space guide plate has been put forward and new insights on the quantity and shape of microscopic minimally invasive tooth preparation has been provided. | Haiyang Yu Yuwei Zhao Junying Li Tian Luo Jing Gao Hongchen Liu Weicai Liu Feng Liu Ke Zhao Fei Liu Chufan Ma Juergen MSetz Shanshan Liang Lin Fan Shanshan Gao Zhuoli Zhu Jiefei Shen Jian Wang Zhimin Zhu Xuedong Zhou | 2019 | International Journal of Oral Science2019，11，4： | 25 |
| 2 | The prognostic and therapeutic implications of circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers in the first-line chemotherapy of HER2-negative metastatic breast cancer显示文摘Background:Epithelial-mesenchymal transition(EMT)is implicated in the metastatic process and presents a chal-lenge to epithelial cell adhesion molecule-based detection of circulating tumor cells(CTCs),which have been demon-strated to be a prognostic indicator in metastatic breast cancer.Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression,no standard recommendations have been established for clinical practice.This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients.Methods:We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes(including epithelial CTCs,biphenotypic epithelial/mesenchymal CTCs,and mesenchymal CTCs)in peripheral blood samples.Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival(PFS)rate were conducted to determine the optimal cut-off values,and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination.Results:For predicting the 1-year PFS rate,the optimal cut-off value of total CTC count was 9.5(Area under the curve[AUC]=0.538,95%confidence interval[CI]=0.418-0.657),and that of the proportion of mesenchymal CTCs was 10.7%(AUC=0.581,95%CI=0.463-0.699).We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%.Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria(6.2 vs.9.9 months,P=0.010).A nomogram was constructed based on the criteria and significant clinicopatho-logical characteristics with a C-index of 0.613(P=0.010).Conclusions: The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer. | Xiuwen Guan Fei Ma Chunxiao Li Shiyang Wu Shangying Hu Jiefen Huang Xiaoying Sun Jiayu Wang Yang Luo Ruigang Cai Ying Fan Qiao Li Shanshan Chen Pin Zhang Qing Li Binghe Xu | 2019 | Cancer Communications2019，39，1： | 15 |
| 3 | A cyclic nucleotide-gated channel mediates cytoplasmic calcium elevation and disease resistance in rice显示文摘The transient elevation of cytoplasmic calcium is essential for pathogen-associated molecular pattern(PAMP)-triggered immunity(PTI).However,the calcium channels responsible for this process have remained unknown.Here,we show that rice CDSI(CELL DEATH and SUSCEPTIBLE to BLAST 1)encoding OsCNGC9;a cyclic nucleotide-gated channel protein,positively regulates the resistance to rice blast disease.We show that OsCNGC9 mediates PAMP-induced Ca2+influx and that this event is critical for PAMPs-triggered ROS burst and induction of PTI-related defense gene expression.We further show that a PTI related receptor-lih cytoplasmic kinase OsRLCK185 physically interacts with and phosphorylates OsCNGC9 to activate its channel activity.Our results suggest a signaling cascade linking pattern recognition to calcium channel activation,which is required for initiation of PTI and disease resistance in rice. | Jiachang Wang Xi Liu An Zhang Yulong Ren Fuqing Wu Gang Wang Yang Xu Cailin Lei Shanshan Zhu Tian Pan Yongfei Wang Huan Zhang Fan Wang Yan-Qiu Tan Yupeng Wang Xin Jin Sheng Luo Chunlei Zhou Xiao Zhang Jinling Liu Shuai Wang Lingzhi Meng Yihua Wang Xi Chen Qibing Lin Xin Zhang Xiuping Guo Zhijun Cheng Jiulin Wang Yunlu Tian Shijia Liu Ling Jiang Chuanyin Wu Ertao Wang Jian-Min Zhou Yong-Fei Wang Haiyang Wang Jianmin Wan | 2019 | Cell Research2019，29，10： | 13 |
| 4 | Macrobenthic Community in the Xiaoqing River Estuary in Laizhou Bay,China显示文摘The macrobenthic community of the Xiaoqing River Estuary and the adjacent sea waters was investigated in May and November 2008,August 2009,and May and September 2010,respectively.A total of 95 species of macrobenthos were identified in the five cruises and most of them were polychaetes(46.39%),mollusks(28.86%) and crustaceans(20.62%).The Shannon-Wiener index of macrobenthos was lower than 2 in 67% sites.Along the stream channel,estuary and the coastal waters,the species of polychaetes reduced gradually,while the abundance increased at first and then decreased.The abundance was the biggest at regions with salinity of 5 20 in the estuary.The species and abundance of mollusks and crustaceans increased gradually.As for seasonal distribution,the species,abundance and biomass were higher in spring and lower in summer and autumn.Contemporaneously compared with Laizhou Bay and Yellow River Estuary,the species of macrobenthos appeared in the Xiaoqing River Estuary were much less,while the percentage of polychaetes was higher.Abundance and biomass were higher in Xiaoqing River estuary,then consequently followed by Laizhou Bay and Yellow River Estuary.The dominant species in Xiaoqing River Estuary was polychaete,and Layzhou Bay mollusk.The community structure characteristics of macrobenthos in the Xiaoqing River Estuary revealed a significant pollution status in this region. | LUO Xianxiang ZHANG Shanshan YANG Jianqiang PAN Jinfen TIAN Lin ZHANG Longjun | 2013 | Journal of Ocean University of China2013，12，3： | 11 |
| 5 | Transcriptional activation and phosphorylation of OsCNGC9 confer enhanced chilling tolerance in rice显示文摘Low temperature is a major environmental factor that limits plant growth and productivity.Although transient elevation of cytoplasmic calcium has long been recognized as a critical signal for plant cold tolerance,the calcium channels responsible for this process have remained largely elusive.Here we report that OsCNGC9,a cyclic nucleotide-gated channel,positively regulates chilling tolerance by mediating cytoplasmic calcium elevation in rice(Oryza sativa).We showed that the loss-of-function mutant of OsCNGC9 is defective in cold-induced calcium influx and more sensitive to prolonged cold treatment,whereas OsCNGC9 overexpression confers enhanced cold tolerance.Mechanistically,we demonstrated that in response to chilling stress,OsSAPK8,a homolog of Arabidopsis thaliana OST1,phosphorylates and activates OsCNGC9 to trigger Ca2+influx.Moreover,we found that the transcription of OsCNGC9 is activated by a rice dehydration-responsive element-binding transcription factor,OsDREB1A.Taken together,our results suggest that OsCNGC9 enhances chilling tolerance in rice through regulating cold-induced calcium influx and cytoplasmic calcium elevation. | Jiachang Wang Yulong Ren Xi Liu Sheng Luo Xiao Zhang Xin Liu Qibing Lin Shanshan Zhu Hua Wan Yang Yang Yu Zhang Bin Lei Chunlei Zhou Tian Pan Yongfei Wang Mingming Wu Ruonan jing Yang Xu Meng Han Fuqing Wu Cailin Lei Xiuping Guo Zhijun Cheng Xiaoming Zheng Yihua Wang Zhigang Zhao Ling Jiang Xin Zhang Yong-Fei Wang Haiyang Wang Jianmin Wan | 2021 | Molecular Plant2021，14，2： | 10 |
| 6 | Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study显示文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials. | Shanshan Qin Hui Yu Xianghua Wu Zhiguo Luo Huijie Wang Si Sun Mingzhu Huang Jia Jin Zhonghua Tao Jie Qiao Yu Feng Jialei Wang Jianhua Chang | 2019 | Chinese Journal of Cancer Research2019，31，2： | 9 |
| 7 | Development and validation of an endoscopic images-based deep learning model for detection with nasopharyngeal malignancies显示文摘Background:Due to the occult anatomic location of the nasopharynx and frequent presence of adenoid hyperpla-sia,the positive rate for malignancy identification during biopsy is low,thus leading to delayed or missed diagnosis for nasopharyngeal malignancies upon initial attempt.Here,we aimed to develop an artificial intelligence tool to detect nasopharyngeal malignancies under endoscopic examination based on deep learning.Methods:An endoscopic images-based nasopharyngeal malignancy detection model(eNPM-DM)consisting of a fully convolutional network based on the inception architecture was developed and fine-tuned using separate training and validation sets for both classification and segmentation.Briefly,a total of 28,966 qualified images were collected.Among these images,27,536 biopsy-proven images from 7951 individuals obtained from January 1st,2008,to December 31st,2016,were split into the training,validation and test sets at a ratio of 7:1:2 using simple randomiza-tion.Additionally,1430 images obtained from January 1st,2017,to March 31st,2017,were used as a prospective test set to compare the performance of the established model against oncologist evaluation.The dice similarity coef-ficient(DSC)was used to evaluate the efficiency of eNPM-DM in automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images,by comparing automatic segmentation with manual segmenta-tion performed by the experts.Results:All images were histopathologically confirmed,and included 5713(19.7%)normal control,19,107(66.0%)nasopharyngeal carcinoma(NPC),335(1.2%)NPC and 3811(13.2%)benign diseases.The eNPM-DM attained an overall accuracy of 88.7%(95%confidence interval(CI)87.8%-89.5%)in detecting malignancies in the test set.In the prospective comparison phase,eNPM-DM outperformed the experts:the overall accuracy was 88.0%(95%CI 86.1%-89.6%)vs.80.5%(95%CI 77.0%-84.0%).The eNPM-DM required less time(40 s vs.110.0±5.8 min)and exhibited encouraging performance in automatic segmentation of nasopharyngeal malignant area from the background,with an average DSC of 0.78±0.24 and 0.75±0.26 in the test and prospective test sets,respectively.Conclusions:The eNPM-DM outperformed oncologist evaluation in diagnostic classification of nasopharyngeal mass into benign versus malignant,and realized automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images. | Chaofeng Li Bingzhong Jing Liangru Ke Bin Li Weixiong Xia Caisheng He Chaonan Qian Chong Zhao Haiqiang Mai Mingyuan Chen Kajia Cao Haoyuan Mo Ling Guo Qiuyan Chen Linquan Tang Wenze Qiu Yahui Yu Hu Liang Xinjun Huang Guoying Liu Wangzhong Li Lin Wang Rui Sun Xiong Zou Shanshan Guo Peiyu Huang Donghua Luo Fang Qiu Yishan Wu Yijun Hua Kuiyuan Liu Shuhui Lv Jingjing Miao Yanqun Xiang Ying Sun Xiang Guo Xing Lv | 2018 | Cancer Communications2018，38，1： | 9 |
| 8 | Efficacy and safety of duloxetine in Chinese breast cancer patients with paclitaxel-induced peripheral neuropathy显示文摘Objective: Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy(PIPN) in Chinese breast cancer patients.Methods:A total of 102 patients with a median age of 50(range,25–60)years,treated in the Department of Medical Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between November 2014 and January 2017 were finally enrolled.Stratified by baseline characteristics,the patients were classified into two groups,receiving either duloxetine or alternative antineurotoxicity drugs.During the course of the paclitaxel regimen,the eligibility criteria included sensory neuropathy,as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events.The treatment consisted of receiving 30 mg duloxetine(for the first 4 weeks)and 60 mg duloxetine for an additional 8 weeks,or any other anti-neurotoxicity drug daily during the same crossover period.The improvement associated with PIPN from the patient’s perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane(FACT-Tax)Scales,which contained questions scored from 0 to 4(0,not at all;4,very much;total score range,0–44).Results:Duloxetine was more effective in decreasing PIPN(odds ratio=5.426;95%confidence interval,1.898–15.514;P=0.002).Between duloxetine group and control group,the median(25th–75th percentiles)decreasing difference in the FACT-Tax pain score was 4(2–6)vs.1(0–4)(P=0.005).Conclusions:Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with PIPN.Non-neuropathy adverse events were mild and similar in both groups.The major toxicities of duloxetine included nausea,constipation,somnolence,dizziness and distention of the eyes.Further examination of the benefits of duloxetine in the prevention of PIPN is required. | Jiani Wang Qing Li Binghe Xu Tongtong Zhang Shanshan Chen Yang Luo | 2017 | Chinese Journal of Cancer Research2017，29，5： | 5 |
| 9 | Disentangling the factors that contribute to variation in forest biomass increments in the mid-subtropical forests of China显示文摘Mid-subtropical forests are the main vegetation type of global terrestrial biomes, and are critical for maintaining the global carbon balance. However, estimates of forest biomass increment in mid-subtropical forests remain highly uncertain. It is critically important to determine the relative importance of different biotic and abiotic factors between plants and soil, particularly with respect to their influence on plant regrowth. Consequently,it is necessary to quantitatively characterize the dynamicspatiotemporal distribution of forest carbon sinks at a regional scale. This study used a large, long-term dataset in a boosted regression tree(BRT) model to determine the major components that quantitatively control forest biomass increments in a mid-subtropical forested region(Wuyishan National Nature Reserve, China). Long-term,stand-level data were used to derive the forest biomass increment, with the BRT model being applied to quantify the relative contributions of various biotic and abiotic variables to forest biomass increment. Our data show that total biomass(t) increased from 4.62 9 106 to 5.30 9 106 t between 1988 and 2010, and that the mean biomass increased from 80.19 ± 0.39 t ha-1(mean ± standard error) to 94.33 ± 0.41 t ha-1in the study region. The major factors that controlled biomass(in decreasing order of importance) were the stand, topography, and soil. Stand density was initially the most important stand factor, while elevation was the most important topographic factor. Soil factors were important for forest biomass increment but have a much weaker influence compared to the other two controlling factors. These results provide baseline information about the practical utility of spatial interpolationmethods for mapping forest biomass increments at regional scales. | Yin Ren Shanshan Chen Xiaohua Wei Weimin Xi Yunjian Luo Xiaodong Song Shudi Zuo Yusheng Yang | 2016 | Journal of Forestry Research2016，27，4： | 5 |
| 10 | New possible silver lining for pancreatic cancer therapy:Hydrogen sulfide and its donors显示文摘As one of the most lethal diseases,pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities.Furthermore,pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found.Although combinations of new drugs,multimodal therapies,and adjuvants prolong survival,most patients still relapse after surgery and eventually die.Consequently,the search for more effective treatments for pancreatic cancer is highly relevant and justified.As a newly re-discovered mediator of gasotransmission,hydrogen sulfide(H2S)undertakes essential functions,encompassing various signaling complexes that occupy key processes in human biology.Accumulating evidence indicates that H2S exhibits bimodal modulation of cancer development.Thus,endogenous or low levels of exogenous H2S are thought to promote cancer,whereas high doses of exogenous H2S suppress tumor proliferation.Similarly,inhibition of endogenous H2S production also suppresses tumor proliferation.Accordingly,H2S biosynthesis inhibitors and H2S supplementation(H2S donors)are two distinct strategies for the treatment of cancer.Unfortunately,modulation of endogenous H2S on pancreatic cancer has not been studied so far.However,H2S donors and their derivatives have been extensively studied as potential therapeutic agents for pancreatic cancer therapy by inhibiting cell proliferation,inducing apoptosis,arresting cell cycle,and suppressing invasion and migration through exploiting multiple signaling pathways.As far as we know,there is no review of the effects of H2S donors on pancreatic cancer.Based on these concerns,the therapeutic effects of some H2S donors and NO-H2S dual donors on pancreatic cancer were summarized in this paper.Exogenous H2S donors may be promising compounds for pancreatic cancer treatment. | Xu Hua Yan Xiao Jianan Sun Bao Ji Shanshan Luo Bo Wu Chao Zheng Peng Wang Fanxing Xu Keguang Cheng Huiming Hua Dahong Li | 2021 | Acta Pharmaceutica Sinica B2021，11，5： | 4 |
| 11 | Goldfish vsx1 inhibits chordamesoderm gene ntl expression at the dorsal midline显示文摘vsx1(visual system homeobox-1),a homeobox gene originally identified from an adult goldfish retinal cDNA library,has been shown to regulate retina progenitor proliferation,differentiation and functional maintenance of bipolar cells in vertebrates.However,in all the examined vertebrate species,vsx1 transcripts can be also detected at the early developmental stage,suggesting that it may play an important role in regulating early embryogenesis as well.Here,we investigated the function of vsx1 in early embryogenesis of goldfish(Carassius auratus) with both overexpression and gene knockdown approaches.It was found that vsx1 overexpression specifically blocked dorsal midline structure for-mation and vsx1 knockdown led to disorganized dorsal midline structure.Whole-mount in situ hy-bridization revealed that the midline expression of ntl,a key regulatory gene for chordamesoderm,was repressed by vsx1 overexpression but enhanced in the vsx1 knockdown.Furthermore,VSX1 protein could bind ntl promoter directly and was sufficient to inhibit ntl promoter-driven reporter gene green fluorescence protein transcription.Together,these results suggested that vsx1 may act to repress ec-topic expression of ntl in neural progenitor cells to ensure neural tube development in a spatially coordinated pattern during early embryogenesis. | LIU ZhengHua CHEN JinHui MA ShanShan TONG Ying LUO Chen | 2009 | Chinese Science Bulletin2009，54，8： | 4 |
| 12 | A new method of frequency-dependent network equivalence for power system显示文摘Electromagnetic transient simulation for large-scale power system is a time-consuming problem.A new frequency-dependent equivalence method is presented in the paper,which might significantly accelerate power system electromagnetic transient simulation.In the method,an effective algorithm is designed to directly transfer the port admittance determinant of external system's mixing matrix into admittance rational function;and the step-by-step strategy for the equivalence of actual large system is put forward,which further reduces the calculation quantities needed.Moreover,the study of multiple real root pole characteristics of admittance transfer function of two-port network is performed and a proposition is achieved.Based on the proposition and residue theorem,the equivalence system for external system corresponding to the admittance rational function is obtained.The computation complexity of the step-by-step equivalence method is about o(┌n/np×T┐)(┌┐ is upper integral operation,n is the total buses number of external system,N P is the total buses number of single step equivalence network,T is single step equivalence time),which indicates that the computation complexity of the method proposed has nearly linear relationship with the buses number of external system,and the method proposed has satisfactory computation speed.Since the mixing matrix of external system includes all the information of external system,therefore,port admittance rational function derived from it can reflect its full frequency characteristic and the equivalence network achieved has high equivalence precision.Moreover,since the port rational function is gained at the condition of the external system without source,which equals stable passive network,it could not show any unstable pole and need not extra measure to make the equivalence system stable.The test results of the samples and comparison with other methods demonstrate that the new method proposed is valid and effective. | LIN JiKeng YAN YiPeng PU TianJiao LUO ShanShan LIU Tao ZHENG WeiHong WANG XuDong | 2012 | Science China(Technological Sciences)2012，55，7： | 3 |
| 13 | Polymorphisms of MTHFR and TYMS predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer显示文摘Background:Breast cancer is a global problem,and a large number of new cases are diagnosed every year.Capecit-abine is effective in patients with metastatic breast cancer(MBC).Hand-foot syndrome(HFS)is a common adverse effect of capecitabine.In this study,we investigated the association between single nucleotide polymorphisms(SNPs)in genes involved in capecitabine metabolism pathways and capecitabine-induced HFS in Chinese patients with MBC to identify some predictive genetic biomarkers.Methods:We selected 3 genes involved in capecitabine metabolism and screened genetic variants in these target genes.We genotyped a total of 22 SNPs in the thymidylate synthase gene(TYMS),the methylene tetrahydrofolate reductase gene(MTHFR),and the ribonucleotide reductase M1 gene(RRM1)in 342 MBC patients treated with capecit-abine-based chemotherapy.The genotype distributions of each SNP in patients with and without HFS were assessed using Pearson’sχ^(2)test,and the relationship between HFS and genotypes of SNPs was determined using logistic regression analysis.The association between SNPs and their corresponding gene expression was analyzed using the Blood expression quantitative trait loci(eQTL)browser online tools.Results:We found 4 positive sites for HFS in the TYMS and MTHFR genes:TYMS rs2606241(P=0.022),TYMS rs2853741(P=0.019),MTHFR rs3737964(P=0.029),and MTHFR rs4846048(P=0.030).Logistic regression analyses showed that the genotype AG of MTHFR rs3737964[odds ratio(OR)=0.54,95%confidence interval(CI)0.31-0.97,P=0.038]and MTHFR rs4846048(OR=0.54,95%CI 0.30-0.98,P=0.042)were protective factors of HFS,whereas the genotype CT of TYMS rs2853741(OR=2.25,95%CI 1.31-3.87,P=0.012)increased the risk of HFS.The association between the genotype GT of TYMS rs2606241(OR=1.27,95%CI 0.73-2.23,P=0.012)and HFS was uncertain.Further eQTL analyses confirmed that the alleles of rs3737964 and rs4846048 affected the gene expression levels of MTHFR in cis.Conclusions:We have identified four potentially useful pharmacogenetic markers,TYMS rs2606241,TYMS rs2853741,MTHFR rs3737964,and MTHFR rs4846048 to predict capecitabine-induced HFS in MBC patients. | Shaoyan Lin Jian Yue Xiuwen Guan Peng Yuan Jiayu Wang Yang Luo Ying Fan Ruigang Cai Qiao Li Shanshan Chen Pin Zhang Qing Li Fei Ma Binghe Xu | 2019 | Cancer Communications2019，39，1： | 3 |
| 14 | Mouse knockout models reveal largely dispensable but context-dependent functions of IncRNAs during development显示文摘 | Xue Han Sai Luo Guangdun Peng Yuyang Lu Guizhong Cui Lichao Liu Pixi Yan Yafei Yin Wei Liu Ran Wang Jiejie Zhang Shanshan Ai Zai Chang Jie Na Aibin He Naihe Jing Xiaohua Shen | 2018 | Journal of Molecular Cell Biology2018，10，2： | 3 |
| 15 | A novel Lyn-like protein tyrosine kinase identified in lamprey and its role in immune response显示文摘The avian sarcoma virus transforming gene(Src)kinase family,a type of nonmreceptor protein tyrosine kinases(nrTPKs),has been reported to play roles in cell growth,division,migration,adhesion,the immune response,and signal transduction berween cells[1,2].The Src family kinases can be divided into three subfamilies based on their conserved domains:SrcA subfamily(Sre,Yes,Fyn,and Fgr,SrcB subfamily(Lck,Hck,Blk,and Lyn),and Frk subfamily[3]. | Tingting Zhao Kedi Luo Xin Liu Shanshan Dong Yinglun Han Meng Gou Peng Su Qingwei Li Ting Zhu | 2020 | Acta Biochimica et Biophysica Sinica2020，52，5： | 2 |
| 16 | Enhancement of α-ketoisovalerate production by relieving the product inhibition of L-amino acid deaminase from Proteus mirabilis显示文摘L-Amino acid deaminase(LAAD) is a key enzyme in the deamination of L-valine(L-val) to produce α-ketoisovalerate(KIV). However, the product inhibition of LAAD is a major hindrance to industrial KIV production.In the present study, a combination strategy of modification of flexible loop regions around the product binding site and the avoidance of dramatic change of main-chain dynamics was reported to reduce the product inhibition.The four mutant PM-LAAD^(M4)(PM-LAAD^(S98A/T105A/S106A/L341A)) achieved a 6.2-fold higher catalytic efficiency and an almost 6.7-fold reduction in product inhibition than the wild-type enzyme. Docking experiments suggested that weakened interactions between the product and enzyme, and the flexibility of the 'lid' structure relieved LAAD product inhibition. Finally, the whole-cell biocatalyst PM-LAAD^(M4) has been applied to KIV production,the titer and conversion rate of KIV from L-val were 98.5 g·L^-1 and 99.2% at a 3-L scale, respectively. These results demonstrate that the newly engineered catalyst can significantly reduce the product inhibition, that making KIV a prospective product by bioconversion method, and also provide the understanding of the mechanism of the relieved product inhibition of PM-LAAD. | Shanshan Pei Xiaobo Ruan Jia Liu Wei Song Xiulai Chen Qiuling Luo Liming Liu Jing Wu | 2020 | Chinese Journal of Chemical Engineering2020，28，8： | 2 |
| 17 | Multifaceted functions of STING in human health and disease:from molecular mechanism to targeted strategy显示文摘Since the discovery of Stimulator of Interferon Genes(STING)as an important pivot for cytosolic DNA sensation and interferon(IFN)induction,intensive efforts have been endeavored to clarify the molecular mechanism of its activation,its physiological function as a ubiquitously expressed protein,and to explore its potential as a therapeutic target in a wide range of immune-related diseases.With its orthodox ligand 2’3’-cyclic GMP–AMP(2’3’-cGAMP)and the upstream sensor 2’3’-cGAMP synthase(cGAS)to be found,STING acquires its central functionality in the best-studied signaling cascade,namely the cGAS–STING–IFN pathway.However,recently updated research through structural research,genetic screening,and biochemical assay greatly extends the current knowledge of STING biology.A second ligand pocket was recently discovered in the transmembrane domain for a synthetic agonist.On its downstream outputs,accumulating studies sketch primordial and multifaceted roles of STING beyond its cytokine-inducing function,such as autophagy,cell death,metabolic modulation,endoplasmic reticulum(ER)stress,and RNA virus restriction.Furthermore,with the expansion of the STING interactome,the details of STING trafficking also get clearer.After retrospecting the brief history of viral interference and the milestone events since the discovery of STING,we present a vivid panorama of STING biology taking into account the details of the biochemical assay and structural information,especially its versatile outputs and functions beyond IFN induction.We also summarize the roles of STING in the pathogenesis of various diseases and highlight the development of small-molecular compounds targeting STING for disease treatment in combination with the latest research.Finally,we discuss the open questions imperative to answer. | Zili Zhang Haifeng Zhou Xiaohu Ouyang Yalan Dong Alexey Sarapultsev Shanshan Luo Desheng Hu | 2023 | Signal Transduction and Targeted Therapy2023，8，1： | 2 |
| 18 | Novel human H7N9 influenza virus in China显示文摘Outbreaks of H7N9 avian influenza in humans in 5 provinces and 2 municipalities of China have reawakened concern that avian influenza viruses may again cross species barriers to infect the human population and thereby initiate a new influenza pandemic.Evolutionary analysis shows that human H7N9 influenza viruses originated from the H9N2,H7N3 and H11N9 avian viruses,and that it is as a novel reassortment influenza virus.This article reviews current knowledge on 11 subtypes of influenza A virus from human which can cause human infections. | Chengmin WANG Jing LUO Jing WANG Wen SU Shanshan GAO Min ZHANG Li XIE Hua DING Shelan LIU Xiaodong LIU Yu CHEN Yaxiong JIA Hongxuan HE | 2014 | Integrative Zoology2014，9，3： | 2 |
| 19 | Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases显示文摘The NLRP3 inflammasome’s core and most specific protein,NLRP3,has a variety of functions in inflammation-driven diseases.Costunolide(COS)is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity,but the principal mechanism and molecular target of COS remain unclear.Here,we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3,altering the ATPase activity and assembly of NLRP3 inflammasome.We declare COS’s great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation.We also reveal that theα-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation.Taken together,NLRP3 is identified as a direct target of COS for its anti-inflammasome activity.COS,especially theα-methylene-γ-butyrolactone motif in COS structure,might be used to design and produce novel NLRP3 inhibitors as a lead compound. | Haowen Xu Jiahao Chen Pan Chen Weifeng Li Jingjing Shao Shanshan Hong Yi Wang Lingfeng Chen Wu Luo Guang Liang | 2023 | Acta Pharmaceutica Sinica B2023，13，2： | 2 |
| 20 | Nonpharmaceutical interventions contribute to the control of COVID-19 in China based on a pairwise model显示文摘Nonpharmaceutical interventions(NPIs),particularly contact tracing isolation and household quarantine,play a vital role in effectively bringing the Coronavirus Disease 2019(COVID-19)under control in China.The pairwise model,has an inherent advantage in characterizing those two NPIs than the classical well-mixed models.Therefore,in this paper,we devised a pairwise epidemic model with NPIs to analyze COVID-19 outbreak in China by using confirmed cases during February 3rde22nd,2020.By explicitly incorporating contact tracing isolation and family clusters caused by household quarantine,our model provided a good fit to the trajectory of COVID-19 infections.We calculated the reproduction number R=1.345(95%CI:1.230-1.460)for Hubei province and R=1.217(95%CI:1.207-1.227)for China(except Hubei).We also estimated the peak time of infections,the epidemic duration and the final size,which are basically consistent with real observation.We indicated by simulation that the traced high-risk contacts from incubated to susceptible decrease under NPIs,regardless of infected cases.The sensitivity analysis showed that reducing the exposure of the susceptible and increasing the clustering coefficient bolster COVID-19 control.With the enforcement of household quarantine,the reproduction number R and the epidemic prevalence declined effectively.Furthermore,we obtained the resumption time of work and production in China(except Hubei)on 10th March and in Hubei at the end of April 2020,respectively,which is broadly in line with the actual time.Our results may provide some potential lessons from China on the control of COVID-19 for other parts of the world. | Xiao-Feng Luo Shanshan Feng Junyuan Yang Xiao-Long Peng Xiaochun Cao Juping Zhang Meiping Yao Huaiping Zhu Michael Y.Li Hao Wang Zhen Jin | 2021 | Infectious Disease Modelling2021，6，1： | 2 |
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