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| 1 | 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 |
| 2 | Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2(HER2)-positive early-stage breast cancer: A real-world retrospective study in Chinese patients显示文摘Objective: To assess the long-term effectiveness and safety of trastuzumab in adjuvant therapy for Chinese patients with early-stage human epidermal growth factor 2(HER2)-positive breast cancer in a real-world setting.Methods: This retrospective observational study analyzed the medical records of HER2-positive breast cancer patients between 2000 and 2012 at the Chinese Academy of Medical Sciences. Patients who received adjuvant chemotherapy alone or adjuvant chemotherapy followed by/combined with trastuzumab were included. The Kaplan-Meier method was used to estimate disease-free survival(DFS) and overall survival(OS). Hazard ratios(HR) and 95% confidence intervals(95% CI) were calculated using the Cox regression model.Results: Of the 1,348 patients analyzed, 909 received chemotherapy alone and 439 received chemotherapy plus trastuzumab. The 3-year, 5-year and 10-year DFS rates were 83.70%, 76.38% and 68.94%, respectively, in the chemotherapy-alone cohort, and 90.21%, 86.19% and 83.45% in the chemotherapy plus trastuzumab cohort. The3-year, 5-year and 10-year OS rates were 96.10%, 91.40% and 81.88% in the chemotherapy-alone cohort, and98.17%, 94.91% and 90.01% in the chemotherapy plus trastuzumab cohort. The chemotherapy plus trastuzumab group had a significantly lower risk of disease recurrence and death than the chemotherapy-alone group(DFS:HR=0.50, 95% CI, 0.37-0.68;P<0.001;OS: HR=0.53, 95% CI, 0.34-0.81;P=0.004) after adjusting for covariates.In the 439 patients treated with trastuzumab, multivariate analysis suggested that lymph node positivity, higher T stages, and hormone receptor-negative status were significantly associated with higher risks of disease recurrence,and lymph node positivity and hormone receptor-negative status were significantly associated with higher risks of death. Grade 3/4 adverse events(incidence ≥1%) were more common in patients receiving trastuzumab(54.44% vs.15.73%).Conclusions: Early-stage HER2-positive breast cancer patients treated with trastuzumab plus adjuvant chemotherapy have a significant survival benefit compared with chemotherapy-alone in real-world settings. Lymph node positivity, hormone receptor-negative status, and higher T stages may be associated with higher risks of recurrence, and effective therapy for patients with these factors is required. | Jihong Guo Qing Li Pin Zhang Peng Yuan Jiayu Wang Fei Ma Ying Fan Ruigang Cai Yang Luo Qiao Li Binghe Xu | 2019 | Chinese Journal of Cancer Research2019，31，5： | 6 |
| 3 | Genomic analyses of metal resistance genes in three plant growth promoting bacteria of legume plants in Northwest mine tailings, China显示文摘To better understand the diversity of metal resistance genetic determinant from microbes that survived at metal tailings in northwest of China, a highly elevated level of heavy metal containing region, genomic analyses was conducted using genome sequence of three native metal-resistant plant growth promoting bacteria(PGPB). It shows that: Mesorhizobium amorphae CCNWGS0123 contains metal transporters from P-type ATPase, CDF(Cation Diffusion Facilitator), Hup E/Ure J and CHR(chromate ion transporter) family involved in copper, zinc, nickel as well as chromate resistance and homeostasis. Meanwhile, the putative Cop A/Cue O system is expected to mediate copper resistance in Sinorhizobium meliloti CCNWSX0020 while Znt A transporter, assisted with putative Czc D, determines zinc tolerance in Agrobacterium tumefaciens CCNWGS0286. The greenhouse experiment provides the consistent evidence of the plant growth promoting effects of these microbes on their hosts by nitrogen fixation and/or indoleacetic acid(IAA) secretion,indicating a potential in-site phytoremediation usage in the mining tailing regions of China. | Pin Xie Xiuli Hao Martin Herzberg Yantao Luo Dietrich H.Nies Gehong Wei | 2015 | Journal of Environmental Sciences2015，27，1： | 5 |
| 4 | Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA显示文摘Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS. | Anjie Zhu Peng Yuan Nanlin Hu Mingzhou Li Wenmiao Wang Xue Wang Jian Yue Jiayu Wang Yang Luo Fei Ma Pin Zhang Qing Li Binghe Xu Shanbo Cao Giuseppe Lippi Yoichi Naito Mohammed A.Osman Gustavo N.Marta Gianluca Franceschini Armando Orlandi | 2021 | Cancer Biology & Medicine2021，18，3： | 4 |
| 5 | Dose-dense paclitaxel plus carboplatin vs.epirubicin and cyclophosphamide with paclitaxel as adjuvant chemotherapy for high-risk triple-negative breast cancer显示文摘Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk. | Qing Li Jiani Wang Yuxin Mu Tongtong Zhang Ying Han Jiayu Wang Qiao Li Yang Luo Fei Ma Ying Fan Pin Zhang Binghe Xulj | 2020 | Chinese Journal of Cancer Research2020，32，4： | 4 |
| 6 | 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 |
| 7 | Genetic polymorphisms of autophagy-related gene 5 (ATG5) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy显示文摘Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy. | Meiying Li Fei Ma Jiayu Wang Qing Li Pin Zhang Peng Yuan Yang Luo Ruigang Cai Ying Fan Shanshan Chen Qiao Li Binghe Xu | 2018 | Cancer Communications2018，38，1： | 2 |
| 8 | Conceptual design of a Cs2LiLaBr6 scintillator‑based neutron total cross section spectrometer on the back‑n beam line at CSNS显示文摘To reduce the experimental uncertainty in the 235 U resonance energy region and improve the detection efficiency for neutron total cross section measurements compared with those obtained with the neutron total cross section spectrometer(NTOX), a dedicated lithium-containing scintillation detector has been developed on the Back-n beam line at the China Spallation Neutron Source. The Fast Scintillator-based Neutron Total Cross Section(FAST) spectrometer has been designed based on a Cs2Li La Br6(CLLB) scintillator considering the γ-ray flash and neutron environment on the Back-n beam line. The response of the CLLB scintillator to neutrons and γ-rays was evaluated with different 6Li/7 Li abundance ratios using Geant4. The neutron-γdiscrimination performance of the CLLB has been simulated considering different scintillation parameters, physical designs,and light readout modes. A cubic 6Li-enriched( > 90%) CLLB scintillator, which has a thickness of 4-9 mm and side length of no less than 50 mm to cover the Φ 50 mm neutron beam at the spectrometer position, has been proposed coupling to a side readout SiPM array to construct the FAST spectrometer. The developed simulation techniques for neutron-γ discrimination performance could provide technical support for other neutron-induced reaction measurements on the Back-n beam line. | Da‑Jun Zhao Song Feng Pin‑Jing Cheng Rong Liu Wen Luo Hao‑Qiang Wang Jie‑Ming Xue Kun Zhu Bo Zheng | 2023 | Nuclear Science and Techniques2023，34，1： | 1 |
| 9 | 基于上皮–间质转化标志物的循环肿瘤细胞表型检测对HER2阴性转移性乳腺癌一线化疗的预后意义显示文摘背景与目的上皮–间质转化(epithelia-mesenchymal,EMT)参与肿瘤细胞的转移,并且对基于上皮细胞黏附分子的循环肿瘤细胞(circulating tumor cells,CTCs)检测技术提出了挑战,CTCs已被证实是转移性乳腺癌的预后指标。虽然有证据表明基于EMT标志物的CTCs异质性与疾病进展相关,但在临床应用方面尚无统一的参考标准。本研究旨在评估基于EMT的动态CTCs检测对转移性乳腺癌患者的预后意义。方法我们从CAMELLIA III期前瞻性研究中招募了108例人表皮生长因子受体2阴性转移性乳腺癌患者,并应用CanPatrol CTC富集技术检测外周血中不同亚型的CTCs(包括上皮型CTCs、混合型上皮/间质CTCs和间质型CTCs)。应用1年无进展生存(progression-free survival,PFS)率作为界值分别寻找CTC总数和间质CTCs比例的受试者工作曲线来确定最佳阈值,并采用Kaplan-Meier分析和Cox比例风险回归分析验证综合考虑CTC总数和间质型CTCs比例制定的诊断标准的预后价值。结果CTC总数的最佳阈值为9.5[曲线下面积(area under the curve,AUC)=0.538,95%置信区间(confidence interval,CI=0.418–0.657)]及间质CTCs比例为10.7%(AUC=0.581,95%CI:0.463–0.699)作为预测1年PFS率的界值。我们采用CTC总数≥10/5 mL且间质CTCs比例>10.7%的联合标准预测PFS。符合联合标准的患者的中位PFS显著短于不符合标准的患者(6.2个月vs.9.9个月,P=0.010)。根据该标准和显著的临床病理学特征绘制列线图,C指数为0.613(P=0.010)。结论CTC总数和间质CTCs比例的联合标准可用于监测转移性乳腺癌患者的治疗耐药性和预测患者预后。 | 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 | 癌症2019，38，9： | 1 |
| 10 | Application of EKF in Laser/Inertial Sensors Localization System显示文摘 | Luo Yahui Jiang Pin Hu Wenwu | | 0，，： | 1 |
| 11 | Distribution of IgM, IgD and IgZ in mandarin fish, Siniperca chuatsi lymphoid tissues and their transcriptional changes after Flavobacterium columnare stimulation显示文摘 | Jingyun Tian Baojian Sun Yanping Luo Yongan Zhang Pin Nie | 2008 | Aquaculture2008，，1： | 1 |
| 12 | OHRank: An Algorithm Integrating Mentality and Influence of Opinion Holder for Opinion Mining显示文摘 | LV Pin ZHONG Luo CAI Dunbo WU Yuntao | 2013 | Chinese Journal of Electronics2013，22，4： | 1 |
| 13 | Immunogenic proteins and their vaccine development potential evaluation in outer membrane proteins(OMPs)of Flavobacterium columnare显示文摘Flavobacterium columnare is a Gram-negative bacterium that causes columnaris disease in freshwater fish worldwide.Many studies have focused on the identification of protective antigens to aid in the development of novel vaccines against the disease.In this study,an immunoblotting approach was employed to identify immunogenic outer membrane proteins(OMPs)from F.columnare in two-dimensional electrophoresis(2-DE)map gels using antibacterial sera obtained from grass carp(Ctenopharyngodon idella),and anti-grass carp-recombinant Ig(rIg)monoclonal antibodies.Five unique immunogenic proteins,including the gliding motility lipoprotein GldJ(GldJ),hypothetical protein FCOL_13420(Fco1),lipoprotein(Lip),F0F1 ATP synthase subunit beta(F0f1)and outer membrane efflux protein precursor(Omep),were characterized.Over-expression of these proteins in Escherichia coli DE3,and their immunogenicity and protective efficacy were evaluated in grass carp.The relative percent survival(RPS)of the groups immunized separately with recombinant GldJ,Lip and Omep was 72%,64%and 68%,respectively when compared to control fish.Up-regulation of immuno-related genes and specific antibodies were detected in immunized fish and sera of immunized fish inhibited the growth of F.columnare.The results suggest that GldJ,Lip and Omep are major protective antigens and may be considered as novel candidates in the development of vaccines against columnaris disease in fish. | Zhang Luo Jianping Fu Nan Li Zhixing Liu Ting Qin Xiaolin Zhang Pin Nie | 2016 | Aquaculture and Fisheries2016，1，1： | 1 |
| 14 | MTHFR和TYMS的多态性预测转移性乳腺癌患者因卡培他滨诱发的手足综合征显示文摘背景与目的乳腺癌是一个全球性问题,每年都会诊断出大量的新发病例。卡培他滨对转移性乳腺癌(metastatic breast cancer,MBC)患者有效。手足综合征(hand-foot syndrome,HFS)是卡培他滨的常见不良反应。在本文中,我们研究了卡培他滨代谢通路相关基因中的单核苷酸多态性(single nucleotide polymorphisms,SNPs)与卡培他滨诱导的中国MBC患者HFS之间的相关性,以确定一些具有预测性的生物标志物基因。方法我们选择了3个参与卡培他滨代谢的基因,并筛选了这些靶基因的遗传变体。我们对342例接受卡培他滨化疗的MBC患者的胸苷酸合酶基因(thymidylate synthase gene,TYMS)、亚甲基四氢叶酸还原酶基因(methylene tetrahydrofolate reductase gene,MTHFR)和核糖核苷酸还原酶M1基因(ribonucleotide reductaseM1gene,RRM1)中的22个SNPs进行了基因分型。使用Pearson’sχ2检验评估患有和不患有HFS的患者中每个SNP的基因型分布,并使用logistic回归分析确定HFS与SNP的基因型之间的相关性。使用血液表达数量定量性状基因座(expression quantitative trait loci,e QTL)Browser在线工具分析了SNP及其对应基因表达之间的相关性。结果我们在TYMS和MTHFR基因中发现了4个HFS阳性位点:TYMS rs2606241(P=0.022)、TYMS rs2853741(P=0.019)、MTHFR rs3737964(P=0.029)和MTHFR rs4846048(P=0.030)。Logistic回归分析显示,MTHFR rs3737964[比值比(odds ratio,OR)=0.54,95%置信区间(confidence interval,CI):0.3–0.97,P=0.038]和MTHFRrs4846048(OR=0.54,95%CI:0.30–0.98,P=0.042)的基因型AG是HFS的保护因素,而TYMS rs2853741的基因型CT(OR=2.25,95%CI:1.31–3.87,P=0.012)增加了HFS的风险。TYMSrs2606241的基因型GT(OR=1.27,95%CI:0.73–2.23,P=0.012)与HFS之间的相关性尚不确定。进一步的e QTL分析证实,rs3737964和rs4846048的等位基因影响顺式MTHFR的基因表达水平。结论我们已经确定了4个潜在有效的药物遗传学标记,TYMS rs2606241、TYMS rs2853741、MTHFR rs3737964和MTHFR rs4846048可以预测卡培他滨诱导的MBC患者的HFS。 | 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 | 癌症2019，38，11： | 1 |
| 15 | Hypoxia signaling in human health and diseases:implications and prospects for therapeutics显示文摘Molecular oxygen(O2)is essential for most biological reactions in mammalian cells.When the intracellular oxygen content decreases,it is called hypoxia.The process of hypoxia is linked to several biological processes,including pathogenic microbe infection,metabolic adaptation,cancer,acute and chronic diseases,and other stress responses.The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia.Hypoxia-inducible factors(HIFs)sense hypoxia to regulate the expressions of a series of downstream genes expression,which participate in multiple processes including cell metabolism,cell growth/death,cell proliferation,glycolysis,immune response,microbe infection,tumorigenesis,and metastasis.Importantly,hypoxia signaling also interacts with other cellular pathways,such as phosphoinositide 3-kinase(PI3K)-mammalian target of rapamycin(mTOR)signaling,nuclear factor kappa-B(NF-κB)pathway,extracellular signal-regulated kinases(ERK)signaling,and endoplasmic reticulum(ER)stress.This paper systematically reviews the mechanisms of hypoxia signaling activation,the control of HIF signaling,and the function of HIF signaling in human health and diseases.In addition,the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted,which would provide novel strategies for the design and development of therapeutic drugs. | Zhen Luo Mingfu Tian Ge Yang Qiaoru Tan Yubing Chen Geng Li Qiwei Zhang Yongkui Li Pin Wan Jianguo Wu | 2022 | Signal Transduction and Targeted Therapy2022，7，8： | 1 |
| 16 | Construction and Genetic Analysis of Murine Hepatitis Virus Strain A59 Nsp16 Temperature Sensitive Mutant and the Revertant Virus显示文摘Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study,we created a MHV-A59 temperature sensitive (ts) mutant Wu'-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu'-ts18(cd) were indistinguishable from the reported ts mutant Wu'-ts18. Then we cultured the ts mutant Wu'-ts18(cd) at non-permissive temperature 39.5°C,which 'forced' the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu'-ts18 (cd) to non-ts phenotype,an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex. | Guo-hui Chang Bao-jun Luo Pin Lu Lei Lin Xiao-yan Wu Jing Li Yi Hu Qing-yu Zhu | 2011 | Virologica Sinica2011，26，1： | 0 |
| 17 | Bipolarized intrinsic faradaic layer on a semiconductor surface under illumination显示文摘Interface charge transfer plays a key role in the performance of semiconductors for different kinds of solar energy utilization,such as photocatalysis,photoelectrocatalysis,photochromism and photo-induced superhydrophilicity.In previous studies,different mechanisms have been used to understand interface charge transfer processes.However,the charge transfer mechanism at the solid/liquid interface remains a controversial topic.Here,taking TiO_(2) as a model,we find and prove,via experiments,the new characteristic of photo-induced bipolarity of the surface layer(reduction faradaic layer and oxidation faradaic layer)on a semiconductor for the first time.Different from energy level positions in the classic surface states transfer mechanism,the potential window of a surface faradaic layer is located out of the forbidden band.Moreover,we find that the reduction faradaic layer and oxidation faradaic layer serve as electron and hole transfer mediators in photocatalysis,while the bipolarity or mono-polarity of the surface layer on a semiconductor depends on the applied potential in photoelectrocatalysis.The new characteristic of bipolarity can also offer new insights into the charge transfer process at the semiconductor/liquid interface for solar energy utilization. | Mengfan Xue Zhiqiang Chu Dongjian Jiang Hongzheng Dong Pin Wang Gengzhi Sun Yingfang Yao Wenjun Luo Zhigang Zou | 2023 | National Science Review2023，10，4： | 0 |
| 18 | Treatment patterns and clinical outcomes in patients with metastatic breast cancer treated with palbociclib-based therapies:real-world data in the Han population显示文摘Background:This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive(ER+)metastatic breast cancer in routine clinical practice.Methods:The clinical data of patients with ER+metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database.The efficacy profile of palbociclib in this Han population was evaluated,especially for various combination regimens.The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed.Results:A total of 186 patients from 89 cities in 18 provinces in China were enrolled.The median progression-free survival(PFS)was similar among different palbociclib-combined groups(P=0.566):10.0 months(95%confidence interval[CI]3.8-16.1)in the+exemestane group,9.7 months(95%CI 6.3-13.1)in the+letrozole group,7.8 months(95%CI 5.5-10.2)in the+fulvestrant group,7.2 months(95%CI 3.2-11.3)in the+toremifene group,and 6.1 months(95%CI 1.2-11.0)in the+anastrozole group.Thirty-four patients(18.3%)had received everolimus for their metastatic disease before the prescription of palbociclib.The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group(50.0%vs.82.2%,P<0.001).Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group(3.4 months vs.8.8 months,P=0.001).After propensity score matching,patients pre-treated with everolimus had similar PFS(4.4 months,95%CI 0.5-8.2)compared with everolimus-naïve patients(6.1 months,95%CI 4.7-7.5,P=0.439).Conclusions:Various palbociclib-based regimens have promising efficacy in ER+metastatic breast cancer in real-world settings,even in patients who had been pre-treated with everolimus. | Hongnan Mo Fei Ma Qing Li Pin Zhang Peng Yuan Jiayu Wang Yang Luo Ruigang Cai Qiao Li Binghe Xu | 2022 | Chinese Medical Journal2022，，14： | 0 |
| 19 | SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication显示文摘Viral infection in respiratory tract usually leads to cell death,impairing respiratory function to cause severe disease.However,the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention,and especially the high-frequency asymptomatic infection increases the risk of virus transmission.Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection.Here,we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein.We found SARS-CoV-2 virus-like particles(trVLP)suppressed cell apoptosis,but the trVLP lacking N protein didn’t.Further study verified that N protein repressed cell apoptosis in cultured cells,human lung organoids and mice.Mechanistically,N protein specifically interacted with anti-apoptotic protein MCL-1,and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1,which stabilized this protein and promoted it to hijack Bak in mitochondria.Importantly,N protein promoted the replications of IAV,DENV and ZIKV,and exacerbated death of IAV-infected mice,all of which could be blocked by a MCL-1 specific inhibitor,S63845.Altogether,we identifed a distinct anti-apoptotic function of the N protein,through which it promoted viral replication.These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction,and indicate a risk of enhanced coinfection with other viruses.We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses. | Pan Pan Weiwei Ge Zhiwei Lei Wei luo Yuqing Liu Zhanwen Guan Lumiao Chen Zhenyang Yu Miaomiao Shen Dingwen Hu Qi Xiang Wenbiao Wang Pin Wan Mingfu Tian Yang Yu Zhen Luo Xulin Chen Heng Xiao Qiwei Zhang Xujing Liang Xin Chen Yongkui Li Jianguo Wu | 2023 | Signal Transduction and Targeted Therapy2023，8，6： | 0 |
| 20 | Thiourea-assisted coating of dispersed copper electrocatalysts on Si photocathodes for solar hydrogen production显示文摘Photoelectrochemical water splitting can convert solar energy into clean hydrogen energy for storage.It is desirable to explore non-precious electrocatalysts for practical applications of a photoelectrode in a large scale.Here,we developed a facile spin-coating and in-situ photoelectrochemical reduction method to prepare a dispersed Cu electrocatalyst on a Si photocathode,which improves the performance remarkably.We find that thiourea in the precursor solution for spin-coating plays an important role in obtaining dispersed Cu particles on the surface of a Si photoelectrode.With thiourea in the precursor,the Cu/Si photocathode shows higher performance than the one without thiourea.Moreover,the Cu/Si photocathode also indicates good stability after 16 h illumination. | Pin Wang Ziyu Yin Linfeng Gao Hui Li Tongyu Zhang Qing Shen Jun Lv Yingfang Yao Wenjun Luo Zhigang Zou | 2020 | Journal of Energy Chemistry2020，29，1： | 0 |
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