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| 1 | Anlotinib has good efficacy and low toxicity: a phase Ⅱ study of anlotinib in pre-treated HER-2 negative metastatic breast cancer显示文摘Objective:Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis.This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.Methods:Patients with HER2-negative breast cancer,who were pre-treated with anthracycline or taxanes in a neoadjuvant,adjuvant,or metastatic setting,and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled.Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred.Simultaneously,5–10 m L of venous blood was collected to perform circulating tumor DNA(ct DNA)testing every 2 treatment cycles.The primary endpoint was the objective response rate(ORR).Secondary endpoints included the disease control rate(DCR),progression-free survival(PFS),overall survival,safety,and biomarkers.Results:Twenty-six eligible patients were enrolled,with a median age of 56(30–75)years.The median follow-up time was 10.5 months.The ORR was 15.4%,the DCR was 80.8%,and the median PFS was 5.22 months(95%confidence interval 2.86–6.24).Fourteen(53.8%)patients survived for more than 10 months.The changes in the detectable ct DNA variant allele frequency were consistent with the tumor response.The most common treatment-related adverse events were hypertension(57.7%),thyroidstimulating hormone elevation(34.6%),and hand-foot syndrome(23.1%).Conclusion:Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated,metastatic HER2-negative breast cancer.The dynamic changes in the ct DNA variant allele fraction may be predictive of the tumor response. | Nanlin Hu Yiran Si Jian Yue Tingting Sun Xue Wang Zhuqing Jia Songlin Gao Qiao Li Yang Shao Jiayu Wang Yang Luo Fei Ma Binghe Xu Peng Yuan | 2021 | Cancer Biology & Medicine2021，18，3： | 11 |
| 2 | Holocene slip rate and paleoearthquake records of the Salt Lake segment of the Northern Zhongtiaoshan Fault, Shanxi Province显示文摘The Northern Zhongtiaoshan Fault is a major deep fault at the southern margin of the Yuncheng Basin. There have been few studies on the fault, and the historical earthquakes are few and weak. However, the intensity of activity on the fault should never be underestimated. Through interpretations of aerial images, topography measurements and excavation of trenches, this paper studied the fault distribution, the surface deformation and the activity of the normal fault south of Salt Lake near the city of Yuncheng. By tracing faults in the three trenches, it was found that there had been at least three large paleoseismic events, at 1–3.5, 3.6–4.4 and 7.4–8.8 ka BP. Employing 14 C dating, we determined the same gravel layers in the uplifted side and downthrown side. Making differential Global Positioning System measurements of the vertical difference and topographic profile, we obtained the mean slip rate of the Northern Zhongtiaoshan Fault since 24.7 ka BP(0.75±0.05 mm/a). Using the results of relevant studies, we calculated the possible vertical fault displacement of one earthquake(2.35 m) and obtained the recurrence interval of characteristic earthquakes as 2940–3360 a after dividing the displacement by the mean slip rate. | SI SuPei LI YouLi Lü ShengHua WANG YiRan | 2014 | Science China Earth Sciences2014，57，9： | 2 |
| 3 | Carrier and microstructure tuning for improving the thermoelectric properties of Ag_(8)SnSe_(6)via introducing SnBr_(2)显示文摘The argyrodite compounds(2 A(12)/B X6 m n n^(m+)+--(Am+=Li^(+),Cu^(+),and Ag^(+);Bn^(+)=Ga^(3+),Si^(4+),Ge^(4+),Sn^(4+),P^(5+),and As^(5+);and X^(2−)=S^(2−),Se^(2−),or Te^(2−)))have attracted great attention as excellent thermoelectric(TE)materials due to their extremely low lattice thermal conductivity(κl).Among them,Ag_(8)SnSe_(6)-based TE materials have high potential for TE applications.However,the pristine Ag_(8)SnSe_(6)materials have low carrier concentration(<1017 cm^(−3)),resulting in low power factors.In this study,a hydrothermal method was used to synthesize Ag_(8)SnSe_(6)with high purity,and the introduction of SnBr_(2)into the pristine Ag_(8)SnSe_(6)powders has been used to simultaneously increase the power factor and decrease the thermal conductivity(κ).On the one hand,a portion of the Br−ions acted as electrons to increase the carrier concentration,increasing the power factor to a value of~698 mW·m^(−1)·K^(−2)at 736 K.On the other hand,some of the dislocations and nanoprecipitates(SnBr_(2))were generated,resulting in a decrease ofκl(~0.13 W·m^(−1)·K^(−1))at 578 K.As a result,the zT value reaches~1.42 at 735 K for the sample Ag8Sn1.03Se5.94Br0.06,nearly 30%enhancement in contrast with that of the pristine sample(~1.09).The strategy of synergistic manipulation of carrier concentration and microstructure by introducing halogen compounds could be applied to the argyrodite compounds to improve the TE properties. | Zhonghai YU Xiuxia WANG Chengyan LIU Yiran CHENG Zhongwei ZHANG Ruifan SI Xiaobo BAI Xiaokai HU Jie GAO Ying PENG Lei MIAO | 2022 | Journal of Advanced Ceramics2022，11，7： | 1 |
| 4 | Classification of clustered microseismic events in a coal mine using machine learning显示文摘Discrimination of seismicity distributed in different areas is essential for reliable seismic risk assessment in mines.Although machine learning has been widely applied in seismic data processing,feasibility and reliability of applying this technique to classify spatially clustered seismic events in underground mines are yet to be investigated.In this research,two groups of seismic events with a minimum local magnitude(ML) of-3 were observed in an underground coal mine.They were respectively located around a dyke and the longwall face.Additionally,two types of undesired signals were also recorded.Four machine learning methods,i.e.random forest(RF),support vector machine(SVM),deep convolutional neural network(DCNN),and residual neural network(ResNN),were used for classifying these signals.The results obtained based on a primary dataset showed that these seismic events could be classified with at least 91% accuracy.The DCNN using seismogram images as the inputs reached the best performance with more than 94% accuracy.As mining is a dynamic progress which could change the characteristics of seismic signals,the temporal variance in the prediction performance of DCNN was also investigated to assess the reliability of this classifier during mining.A cascaded workflow consisting of database update,model training,signal prediction,and results review was established.By progressively calibrating the DCNN model,it achieved up to 99% prediction accuracy.The results demonstrated that machine learning is a reliable tool for the automatic discrimination of spatially clustered seismicity in underground mining. | Yi Duan Yiran Shen Ismet Canbulat Xun Luo Guangyao Si | 2021 | Journal of Rock Mechanics and Geotechnical Engineering2021，13，6： | 1 |
| 5 | Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer显示文摘Objective:The choice of chemotherapeutic regimen for triple-negative breast cancer(TNBC)remains controversial.Homologous recombination deficiency(HRD)has attracted increasing attention in informing chemotherapy treatment.This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy.Methods:Chinese patients with TNBC who received chemotherapy between May 1,2008 and March 31,2020 were retrospectively analyzed with a customized 3D-HRD panel.HRD positivity was defined by an HRD score≥30 or deleterious BRCA1/2 mutation.A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort(NCT01150513)and a metastatic cohort,and 189 patients with available clinical and tumor sequencing data were included.Results:In the entire cohort,49.2%(93/189)of patients were identified as HRD positive(40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of≥30).In the first-line metastatic setting,platinum therapy was associated with longer median progression-free survival(mPFS)than platinum-free therapy[9.1 vs.3.0 months;hazard ratio(HR),0.43;95%confidence interval 0.22–0.84;P=0.01].Among HRD-positive patients,the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy(13.6 vs.2.0 months;HR,0.11;P=0.001).Among patients administered a platinum-free regimen,HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients(P=0.02;treatment-biomarker P-interaction=0.001).Similar results were observed in the BRCA1/2-intact subset.In the adjuvant setting,HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy(P=0.05,P-interaction=0.02).Conclusions:HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings. | Yimeng Chen Xue Wang Feng Du Jian Yue Yiran Si Xiaochen Zhao Lina Cui Bei Zhang Ting Bei Binghe Xu Peng Yuan | 2023 | Cancer Biology & Medicine2023，20，2： | 1 |
| 6 | Per1/Per2 double knockout transcriptome analysis reveals circadian regulation of hepatic lipid metabolism显示文摘Scope: Circadian disorder and high-fat diet(HFD)can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout(DKO)on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid(DHA)substitution. Methods and results: Both wild type(WT)and DKO male C57BL/6 mice were fed with normal chow diet(CON), HFD, or HFD with DHA substitution(AO)for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time(ZT)0(7:00 am)or ZT12(7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/-mice, which was improved by DHA substitution. Conclusions: Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice. | Yiran Bu Si Chen Mengcheng Ruan Libang Wu Hualin Wang Na Li Xiuju Zhao Xiaoli Yu Zhiguo Liu | 2023 | Food Science and Human Wellness2023，12，5： | 0 |
| 7 | Bioinformatics analysis of human kallikrein 5 (KLK5) expression in metaplastic triple‐negative breast cancer显示文摘Background:Metaplastic breast carcinoma(MBC)is a rare breast cancer subtype;most cases are triple‐negative breast cancers(TNBCs)and are poorly responsive to conventional systemic therapy.Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered.We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.Methods:Differentially expressed genes(DEGs)in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407.The GSE76275 data set and The Cancer Genome Atlas(TCGA)database were used to screen DEGs in TNBC and non‐TNBC.Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology(GO)analysis of DEGs.Online databases,including UALCAN,GEPIA,HPA,Breast Cancer Gene‐Expression Miner,and quantitative PCR and western blot,were used to examine KLK5 messenger RNA and protein expression in breast cancer.Analysis of KLK5‑associated genes was performed with TCGA data,and the LinkedOmics database was used to detect the genes co‐expressed with KLK5.STRING(Search Tool for the Retrieval of Interacting Genes)and Cytoscape were used to screen for hub genes.Kaplan‑Meier plotter was used for survival analysis.Results:KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC.The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC.KEGG and GO analyses revealed that epithelial‐to‐mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1and DSG3 influence metaplastic TNBC progression. Prognosis analysis showedthat only low expression of KLK5 in metaplastic TNBC had clinical significance.Conclusion: Our research indicated that KLK5 may be a pivotal moleculewith a key role in the mechanism of tumorigenesis in metaplastic TNBC. | Yue Song Guiying Bai Xiaoqing Li Liyan Zhou Yiran Si Xiaohui Liu Yilin Deng Yehui Shi | 2023 | Cancer Innovation2023，2，5： | 0 |
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