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| 1 | Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice显示文摘最近的研究开始在心脏的肥大和机能障碍的致病揭示了 microRNAs (miRNAs ) 的关键角色。在这研究,我们测试了是否转变生长 factor-β(TGF-β) 调整 miRNA 在心脏的肥大和心失败(HF ) 的发展起了一个枢轴的作用。我们观察到 miR-27b 是在 cardiomyocyte 特定的 Smad4 猛烈老鼠的心的 upregulated,它开发了心脏的肥大。在 vitro,实验证明 miR-27b 表示能被 TGF-β 禁止; 1 并且它的 overexpression 支持了 hypertrophic 房间生长,当 miR-27b 抑制导致了 hypertrophic 房间的抑制时,生长由 phenylephrine (PE ) 引起了处理。而且,有 miR-27b 的 cardiomyocyte 特定的 overexpression 的转基因的老鼠的分析表明 miR-27b overexpression 是足够的导致心脏的肥大和机能障碍。我们验证了 peroxisome 激活 proliferator 的 receptor-γ(PPAR-γ) 作为在 cardiomyocyte 的 miR-27b 的一个直接目标。一致地, miR-27b 转基因的老鼠显著地显示了 PPAR-γ 的底层;比控制鼠标。而且,在用在一只 pressure-overload-induced 老鼠的特定的 antagomir 的 miR-27b 的 vivo silencing, HF 的模型增加了心脏的 PPAR-γ表示,稀释心脏的肥大和机能障碍。我们的学习的结果表明那 TGF-β 1-regulated miR-27b 涉及心脏的肥大的规定,并且为心脏病作为一个有效治疗学的目标验证 miR-27b。 | Jian Wang Yao Song Yan Zhang Han Xiao Qiang Sun Ning Hou Shuilong Guo Youliang Wang Kaiji Fan Dawei Zhan Lagabaiyila Zha Yang Cao Zhenhua Li Xuan Cheng Youyi Zhang Xiao Yang | 2012 | Cell Research2012，22，3： | 36 |
| 2 | Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes显示文摘 | Xiao-Lei Shi Yimeng Gao YupengYan HuchengMa Lulu Sun Pengyu Huang Xuan Ni Ludi Zhang Xin Zhao Haozhen Ren Dan Hu Yan Zhou Feng Tian Yuan Ji Xin Cheng Guoyu Pan Yi-Tao Ding LijianHui | 2016 | Cell Research2016，26，2： | 31 |
| 3 | Homology-mediated end joining-based targeted integration using CRISPR/Cas9显示文摘 | Yao, Xuan Wang, Xing Hu, Xinde Liu, Zhen Liu, Junlai Zhou, Haibo Shen, Xiaowen Wei, Yu Huang, Zijian Ying, Wenqin Wang, Yan Nie, Yan-Hong Zhang, Chen-Chen Li, Sanlan Cheng, Leping Wang, Qifang Wu, Yan Huang, Pengyu Sun, Qiang Shi, Linyu Yang, Hui | 2017 | Cell Research2017，27，6： | 28 |
| 4 | One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs显示文摘CRISPR/Cas9 系统是一个有效编辑基因的方法,但是编辑基因的动物的多数显示出 mosaicism,与编辑仅仅在房间的部分发生。这里,我们证明那单个基因或多重基因能被 Cas9 mRNA 和多重邻近的单个指南的 RNA 的 zygotic 注射完全在老鼠和猴子胚胎击倒(spaced 10-200 bp 分开) 指向仅仅一把单个钥匙每基因的 exon。个别地在 Y 染色体上跟随八基因的指向的删除的 F0 老鼠的 Phenotypic 分析在产生猛烈老鼠表明了这条途径的坚韧性。重要地,这条途径在高效率交付完全的基因大美人(Arntl 上的 100% 并且 91% 在 Prrt2 上) 在猴子胚胎。最后,我们能在一个单个步骤产生一只完全的 Prrt2 猛烈猴子,表明在很快建立编辑基因的猴子模型的这条途径的实用性。 | Erwei Zuo Yi-Jun Cai Kui Li Yu Wei Bang-An Wang Yidi Sun Zhen Liu Jiwei Liu Xinde Hu Wei Wei Xiaona Huo Linyu Shi Cheng Tang Dan Liang Yan Wang Yan-Hong Nie Chen-Chen Zhang Xuan Yao Xing Wang Changyang Zhou Wenqin Ying Qifang Wang Ren-Chao Chen Qi Shen Guo-Liang Xu Jinsong Li Qiang Sun Zhi-Qi Xiong Hui Yang | 2017 | Cell Research2017，27，7： | 21 |
| 5 | Human ESC-derived expandable hepatic organoids enable therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury显示文摘We report the generation of human ESC-derived,expandable hepatic organoids(hEHOs)using our newly established method with wholly defined(serum-free,feeder free)media.The hEHOs stably maintain phenotypic features of bipotential liver stem/progenitor cells that can differentiate into functional hepatocytes or cholangiocytes.The hEHOs can expand for 20 passages enabling large scale expansion to cell numbers requisite for industry or clinical programs.The cells from hEHOs display remarkable repopulation capacity in injured livers of FRG mice following transplantation,and they differentiate in vivo into mature hepatocytes.If implanted into the epididymal fat pads of immune-deficient mice,they do not generate non-hepatic lineages and have no tendency to form teratomas.We further develop a derivative model by incorporating human fetal liver mesenchymal cells(hFLMCs)into the hEHOs,referred to as hFLMC/hEHO,which can model alcoholic liver disease-associated pathophysiologic changes,including oxidative stress generation,steatosis,inflammatory mediators release and fibrosis,under ethanol treatment.Our work demonstrates that the hEHOs have considerable potential to be a novel,ex vivo pathophysiological model for studying alcoholic liver disease as well as a promising cellular source for treating human liver diseases. | Shuyong Wang Xuan Wang Zuolong Tan Yuxin Su Juan Liu Mingyang Chang Fang Yan Jie Chen Tao Chen Chuanjiang Li Jie Hu Yunfang Wang | 2019 | Cell Research2019，29，12： | 20 |
| 6 | Relation between electricity structure of the crust and deformation of crustal blocks on the northeastern margin of Qinghai-Tibet Plateau显示文摘Study on the electricity structure along a magnetotelluric (MT) sounding profile on the northeastern margin of Qinghai-Tibet Plateau indicates that four crustal blocks can be de-termined from southwest to northeast, namely Bayan Har block (BH), Qin-Qi block (QQ), Hai-yuan block (HY) or the North-South seismotectonic belt and Ordos block (OD). The BH, QQ and OD blocks display a similar electricity structure of the crust. The upper crust represents a high- resistivity layer and the upper part of lower crust represents a low-resistivity layer with the resis-tivity increasing gradually with depth from the lower part of lower crust to the upper mantle. The electricity structure of the crust in these three blocks is similar to that in the complete blocks on the southern and eastern margins of the Qinghai-Tibet Plateau and belongs to normal electricity layering of the crust in slightly deformed or complete intracontinental blocks. The crust in HY block as a boundary zone has been significantly deformed, hence its electricity layering was de-stroyed and the structure was complex and the block became a recent tectonically active and great seismo-active region. The contact belts between the blocks on the northeastern margin of Qinghai-Tibet Plateau exhibit both upthrusting outward and strike-slip movement different from those on the southern and eastern margins of the plateau. The genesis of the low-resistivity layer in the crust is analyzed and the thickness of the lithosphere is estimated in the paper. | ZHAO Guoze TANG Ji ZHAN Yan CHEN Xiaobin ZHUO Xianjun WANG Jijun XUAN Fei DENG Qianhui ZHAO Junmeng | 2005 | Science China Earth Sciences2005，48，10： | 20 |
| 7 | Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol显示文摘Menopause is associated with dyslipidemia and an increased risk of cardio-cerebrovascular disease.The classic view assumes that the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen.In addition to a decrease in estrogen, circulating follicle-stimulating hormone (FSH)levels become elevated at menopause.In this study,we find that blocking FSH reduces serum cholesterol via inhibiting hepatic cholesterol biosynthesis.First,epidemiological results show that the serum FSH levels are positively correlated with the serum total cholesterol levels,even after adjustment by considering the effects of serum estrogen,in addition,the prevalence of hypercholesterolemia is significantly higher in peri-menopausal women than that in premenopausal women.Furthermore,we generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX)mice,in which a normal level of estrogen (E2)was maintained by exogenous supplementation. Consistently,the results indicate that FSH,independent of estrogen,increases the serum cholesterol level in this mouse model. Moreover,blocking FSH signaling by anti-FSHβ antibody or ablating the FSH receptor (FSHR)gene could effectively prevent hypercholesterolemia induced by FSH injection or high-cholesterol diet feeding.Mechanistically,FSH,via binding to hepatic FSHRs, activates the Gi2α/β-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter,thus preventing FoxO1 from repressing SREBP-2 gene transcription.This effect,in turn,results in the upregulation of SREBP-2,which drives HMGCR nascent transcription and de novo cholesterol biosynthesis,leading to the increase of cholesterol accumulation.This study uncovers that blocking FSH signaling might be a new strategy for treating hypercholesterolemia during menopause, particularly for women in peri-menopause characterized by FSH elevation only. | Yanjing Guo Meng Zhao Tao Bo Shizhan Ma Zhongshang Yuan Wenbin Chen Zhao He Xu Hou Jun Liu Zhenhai Zhang Qiang Zhu Qiangxiu Wang Xiaoyan Lin Zhongli Yang Min Cui Lu Liu Yujie Li Chunxiao Yu Xiaoyi Qi Qian Wang Haiqing Zhang Qingbo Guan Lifang Zhao Shimeng Xuan Huili Yan Yanliang Lin Li Wang Qihang Li Yongfeng Song Ling Gao Jiajun Zhao | 2019 | Cell Research2019，29，2： | 16 |
| 8 | Aberrant TGF-β1 signaling contributes to the development of primary biliary cirrhosis in murine model显示文摘AIM:To investigate whether transforming growth factor-β1(TGF-β1)signaling pathway is involved in the pathogenesis of primary biliary cirrhosis(PBC).METHODS:A murine model of PBC was developed by injection of polyinosinic polycytidylic acids(polyⅠ:C)in C57BL/6 mice,and the liver expressions of TGFβ1,TGF-βreceptorⅠ(TβRⅠ),TGF-βreceptorⅡ(TβRⅡ),p-Smad2/3,monoclonalα-smooth muscle actin antibody(α-SMA)andα1(Ⅰ)collagen in the mouse model and control mice were evaluated by immunohistochemistry,immunoblotting and real-time polymerase chain reaction(RT-PCR).Lymphocyte subsets in liver were analyzed using flow cytometry.RESULTS:The mouse model had several key phenotypic features of human PBC,including elevated levels of alkaline phosphatase,antimitochondrial antibodies,portal bile ducts inflammation,and progressive collagen deposition.Compared with control mice,protein and mRNA levels of TGFβ1,TβRⅠ,TβRⅡ,p-Smad2/3,α-SMA andα1(Ⅰ)collagen in liver(1.7±0.4 vs 8.9±1.8,0.8±0.2 vs 5.1±1.5,0.6±0.01 vs5.1±0.1,0.6±0.3 vs 2.0±0.3,0.9±0.4 vs 3.4±0.6,0.8±0.4 vs 1.7±0.3,1.1±1.2 vs 11.8±0.6,P<0.05),and the total number and percentage of CD4+CD25+FOXP3+and CD8+lymphocytes(0.01±0.001vs 0.004±0.00,0.12±0.04 vs 0.52±0.23,P<0.01)were higher in the mouse model.CONCLUSION:TGFβ1 might play a dual role in the development of PBC:it suppresses inflammatory response but operates to enhance fibrogenesis.The aberrant activity of TGF-β1 signaling contributes to the development of PBC. | Bin Liu Xuan Zhang Feng-Chun Zhang Jin-Bao Zong Wen Zhang Yan Zhao | 2013 | World Journal of Gastroenterology2013，19，35： | 14 |
| 9 | Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells显示文摘AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie(XTSJ) decoction on gastric cancer stem-like cells(GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor(VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells(GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction.RESULTS: CD44+ GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth(GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density(MVD)(GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium-(82.87% ± 6.53%) and high-dose XTSJ groups(77.43% ± 7.34%) was detected at 24 h in the CD44+ GCSCs group compared with the saline group(95.42% ± 5.76%) and the low-dose XTSJ group(90.74% ± 6.57%)(P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44- groups; significant differences were only detected in the high-dose XTSJ group at 48 h(78.57% ± 6.94%) and 72 h(72.12% ± 7.68%) when compared with the other CD44- groups(P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium(1.76 ± 0.15) and high-dose XTSJ(1.33 ± 0.081) groups compared with the GCSCs control group(2.72 ± 0.25) and the low-dose XTSJ group(2.51 ± 0.25)(P < 0.05). We also detected a remarkable decrease of MVD in the medium-(7.10 ± 0.60) and high-dose XTSJ(5.99 ± 0.47) groups compared with the GCSC control group(8.15 ± 0.42) and the low-dose XTSJ group(8.14 ± 0.46)(P < 0.05). Additionally, CD44 expression was decreased in these groups [medium-(4.43 ± 0.45) and high-dose XTSJ groups(3.56 ± 0.31) vs the GCSC control(5.96 ± 0.46) and low dose XTSJ groups(5.91 ± 0.38)](P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression.CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1. | Bing Yan Long Liu Ying Zhao Li-Juan Xiu Da-Zhi Sun Xuan Liu Ye Lu Jun Shi Yin-Cheng Zhang Yong-Jin Li Xiao-Wei Wang Yu-Qi Zhou Shou-Han Feng Can Lv Pin-Kang Wei Zhi-Feng Qin | 2014 | World Journal of Gastroenterology2014，20，36： | 14 |
| 10 | Effects of Angelica dahurica on obesity and fatty liver in mice显示文摘Angelica dahurica(A. dahurica) is a traditional Chinese medicinal plant being used in clinical practice. The present study demonstrated that A. dahurica could reduce white-fat weight in high-fat-diet hyperlipidemic mice, decrease total cholesterol and triglyceride concentrations in the livers of both high-fat-diet and Triton WR1339 induced hyperlipidemic mice, and enhance the total hepatic lipase activities of them. These findings were further supported by the results derived from the experiments with Hep G2 cells in vitro. In addition, the proteins related to lipids metabolism were investigated using LC-MS/MS, indicating that genes of lipid metabolism and lipid transport were regulated by A. dhurica. The results from LC-MS/MS were further conformed by Western blot and real time PCR assays. A. dahurica could down-regulate the expression of catalase(CAT) and sterol carrier protein2(SCP2) and up-regulate the expression of lipid metabolism related genes-lipase member C(LIPC) and peroxisome proliferator-activated receptor gamma(PPARγ). In the Triton WR1339 mouse liver and Hep G2 cells in vitro, A. dahurica was able to increase the expression of LIPC and PPARγ, confirming the results from in vivo experiments. Imperatorin showed the same activity as A. dahurica, suggesting it was one of the major active ingredients of the herb. In conclusion, our work represented a first investigation demonstrating that A. dahurica was able to regulate lipid metabolism and could be developed as a novel approach to fighting against fatty liver and obesity. | LU Xi YUAN Zhi-Yi YAN Xiao-Jin LEI Fan JIANG Jing-Fei YU Xuan YANG Xiu-Wei XING Dong-Ming DU Li-Jun | 2016 | Chinese Journal of Natural Medicines2016，14，9： | 11 |
| 11 | Comparative proteogenomic analysis of the Leptospira interrogans virulence-attenuated strain IPAV against the pathogenic strain 56601显示文摘稀释毒力的螺旋体 interrogans serovar Lai 紧张 IPAV 被延长实验室经过从在中国孤立的高度剧毒的祖先的紧张导出。我们学习了 IPAV 的基因变化对病原的 L 经由比较分析使它变为无毒害。interrogans serovar Lai 紧张 56601。IPAV 紧张的完全的染色体顺序决心、使用与作比较,然后修正并且重新注解紧张 56601 的染色体顺序。除了他们的高度类似的 genomic,结构和基因顺序, 33 插入的一个总数, 53 删除和 301 个单个核苷酸的变化(SNV ) 在整个直接影响 101 基因的 IPAV 的染色体被检测,在他们的 5 ′ 的任何一个;在上游的区域或在他们的编码区域以内。在他们之中, 44 功能的基因的多数涉及信号 transduction,压力反应, transmembrane 运输和氮新陈代谢。基于量的液体,层析(LC )-MS/MS 数据揭示了的比较 proteomic 分析在 orthologs 的 1 627 选择的对之中,在 IPAV 的 174 基因拉紧,这是 upregulated,与主要在精力的班上的丰富生产和类脂化合物新陈代谢。相反,在紧张 56601 的 228 基因是 upregulated,与在蛋白质翻译和 DNA 复制 / 修理的范畴充实的多数。 genomic 和 proteomic 途径的联合在批评基因说明了那改变的表情或变化,例如编码 Ser/Thr kinase ,碳饥饿蛋白质 CstA ,夫酸安合成酶,GTP有约束力的蛋白质 BipA , ribonucleotide-diphosphate reductase 和磷酸盐 transporter 的那些,并且在脂蛋白或外部膜蛋白质的翻译侧面的改变是可能的在紧张 IPAV 说明毒力变细。 | Yi Zhong Xiao Chang Xing-Jun Cao Yan Zhang Huajun Zheng Yongzhang Zhu Chengsong Cai Zelin Cui Yunyi Zhang Yuan-Yuan Li Xiu-Gao Jiang Guo-Ping Zhao Shengyue Wang Yixue Li Rong Zeng Xuan Li Xiao-Kui Guo | 2011 | Cell Research2011，21，8： | 10 |
| 12 | The association between the baseline bone resorption marker CTX and incident dysglycemia after 4 years显示文摘Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin(OCN) in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen(CTX) and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant(NGT) women at baseline were invited for follow-up. The incidence of diabetes and prediabetes(collectively defined as dysglycemia) was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3%(95% confidence interval(CI), 6.8%–30.7%)] compared with the lower [31.0%(95%CI, 17.2%–46.1%)] and upper [46.5%(95% CI, 31.2%–62.6%)] tertiles of CTX, with a significant difference seen between the middle and upper tertiles(P = 0.002 5). After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09(95% CI, 1.73–28.99) when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia. | Ting-ting Liu Dong-mei Liu Yan Xuan Lin Zhao Li-hao Sun Dian-dian Zhao Xiao-feng Wang Yang He Xing-Zhi Guo Rui Du Ji-qiu Wang Jian-min Liu Hong-yan Zhao Bei Tao | 2017 | Bone Research2017，5，3： | 10 |
| 13 | Whole-Genome Resequencing of a Worldwide Collection of Rapeseed Accessions Reveals the Genetic Basis of Ecotype Divergence显示文摘Rapeseed (Brassica napus),an important oilseed crop,has adapted to diverse climate zones and latitudes by forming three main ecotype groups,namely winter,semiwinter,and spring types. However,genetic variations underlying the divergence of these ecotypes are largely unknown. Here,we report the global pattern of genetic polymorphisms in rapeseed determined by resequencing a worldwide collection of 991 germplasm accessions.A total of 5.56 and 5.53 million singlenucleotide polymorphisms (SNPs)as Well as 1.86 and 1.92 million InDels were identified by mapping reads to the reference genomes of 'Darmor-bzh'and 'Tapidor,'respectively.We generated a map of allelic drift paths that shows splits and mixtures of the main populations,and revealed an asymmetric evolution of the two subgenomes of B.napus by calculating the genetic diversity and linkage disequilibrium parameters.Selective-sweep analysis revealed genetic changes in genes orthologous to those regulating various aspects of plant development and response to stresses.A genome-wide association study identified SNPs in the promoter regions of FLOWERING LOCUS T and FLOWERING LOCUS C orthologs that corresponded to the different rapeseed ecotype groups. Our study provides important insights into the genomic footprints of rapeseed evolution and flowering-time divergence among three ecotype groups,and will facilitate screening of molecular markers for accelerating rapeseed breeding. | Dezhi Wu Zhe Liang Tao Yan Ying Xu Lijie Xuan Juan Tang Gang Zhou Ulrike Lohwasser Shuijin Hua Haoyi Wang Xiaoyang Chen Qian Wang Le Zhu Antony Maodzeka Nazim Hussain Zhilan Li Xuming Li Imran Haider Shamsi Ghulam Jilani Linde Wu Hongkun Zheng Guoping Zhang Boulos Chalhoub Lisha Shen Hao Yu Lixi Jiang | 2019 | Molecular Plant2019，12，1： | 10 |
| 14 | Mycoplasma pneumoniae Macrolide Resistance and MLVA Typing in Children in Beijing,China,in 2016:Is It Relevant?显示文摘Objective The aim of this study is to investigate the macrolide resistance rate and molecular type with multiple-locus variable-number tandem-repeat analysis(MLVA)of Mycoplasma pneumoniae of Beijing in 2016 in pediatric patients.Methods Real-time quantitative polymerase chain reaction(PCR)was used to identify M.pneumoniae,and MLVA was performed.The domain V of the 23 S rRNA was sequenced to detect macrolide-resistant point mutations.We also investigated the activities of antibiotics against M.pneumoniae isolates in vitro.Results The PCR detection rate of M.pneumoniae in children in Beijing was 40%,and the macrolide resistance rate was 66%.The A2063 G mutation in the 23 S rRNA V region is the dominant mutation(137/146,93.84%),whereas the A2064 G mutation is rare(9/146,6.16%).Seventy-three samples were typed successfully by MLVA typing,including 86.3%(63/73)were MLVA type 4-5-7-2,and 13.7%(10/73)were MLVA type 3-5-6-2.No other types were found.No strains were resistant to levofloxacin or tetracycline.Conclusion In 2016,a specific decrease in the macrolide resistance rate occurred in Beijing.The detection rate and macrolide resistance rate of outpatients are lower than those of inpatients.The A2063 G mutants M.pneumoniae have high levels of resistance to erythromycin and azithromycin.The primary MLVA type is 4-5-7-2,followed by 3-5-6-2.No other MLVA types were detected.No strains resistant to tetracycline or levofloxacin were found in vitro. | DOU Hai Wei TIAN Xiu Jun XIN De Li WEI Ran ZHOU Wei WANG Hong QIN Xuan Guang SHAO Jun Yan XU Bao Ping GE Li Xia SHI Da Wei | 2020 | Biomedical and Environmental Sciences2020，33，12： | 9 |
| 15 | Detection of Pseudorabies Virus Antibodies in Human Encephalitis Cases显示文摘Pseudorabies virus(PRV),a veterinary pathogen that infects domestic animals as well as wild animals such as wild boar and feral swine,was recently reported to infect human and led to endophthalmitis and encephalitis.A retrospective seroepidemiologic survey was conducted using 1,335 serum samples collected from patients with encephalitis and ELISA positive rates were 12.16%,14.25%,and 6.52%in 2012,2013,and 2017,respectively. | LI Xiang Dong FU Shi Hong CHEN Ling Yan LI Fan DENG Jun Hua LU Xuan Cheng WANG Huan Yu TIAN Ke Gong | 2020 | Biomedical and Environmental Sciences2020，33，6： | 9 |
| 16 | Hard X-ray Imager (HXI) onboard the ASO-S mission显示文摘Hard X-ray Imager(HXI)is one of the three scientific instruments onboard the Advanced Spacebased Solar Observatory(ASO-S)mission,which is proposed for the 25th solar maximum by the Chinese solar community.HXI is designed to investigate the non-thermal high-energy electrons accelerated in solar flares by providing images of solar flaring regions in the energy range from 30 keV to 200 keV.The imaging principle of HXI is based on spatially modulated Fourier synthesis and utilizes about 91 sets of bi-grid sub-collimators and corresponding LaBr3 detectors to obtain Fourier components with a spatial resolution of about 3 arcsec and a time resolution better than 0.5 s.An engineering prototype has been developed and tested to verify the feasibility of design.In this paper,we present background,instrument design and the development and test status of the prototype. | Zhe Zhang Deng-Yi Chen Jian Wu Jin Chang Yi-Ming Hu Yang Su Yan Zhang Jian-Ping Wang Yao-Ming Liang Tao Ma Jian-Hua Guo Ming-Sheng Cai Yong-Qiang Zhang Yong-Yi Huang Xiao-Yan Peng Zong-Bin Tang Xuan Zhao Hong-He Zhou Lian-Guo Wang Jing-Xing Song Miao Ma Guang-Zhou Xu Jian-Feng Yang Di Lu Ying-Hong He Jin-You Tao Xiao-Long Ma Bao-Gang Lv Yan-Ping Bai Cai-Xia Cao Yu Huang Wei-Qun Gan | 2019 | Research in Astronomy and Astrophysics2019，19，11： | 9 |
| 17 | Clinical and genetic findings in a Chinese family with VDR-associated hereditary vitamin D-resistant rickets显示文摘Hereditary vitamin D-resistant rickets(HVDRR) is a rare autosomal recessive disorder characterized by severe rickets,hypocalcemia,hypophosphatemia,secondary hyperparathyroidism,and elevated alkaline phosphatase.This disorder is caused by homogeneous or heterogeneous mutations affecting the function of the vitamin D receptor(VDR),which lead to complete or partial target organ resistance to the action of 1,25-dihydroxy vitamin D.A non-consanguineous family of Chinese Han origin with one affected individual demonstrating HVDRR was recruited,with the proband evaluated clinically,biochemically and radiographically.To identify the presence of mutations in the VDR gene,all the exons and exon–intron junctions of the VDR gene from all family members were amplified using PCR and sequenced.The proband showed rickets,progressive alopecia,hypocalcemia,hypophosphatemia,secondary hyperparathyroidism,and elevated alkaline phosphatase.She also suffered from epilepsy,which is rarely seen in patients with HVDRR.Direct sequencing analysis revealed a homozygous missense mutation c.122G4A(p.C41Y) in the VDR gene of the proband,which is located in the first zinc finger of the DNA-binding domain.Both parents had a normal phenotype and were found to be heterozygous for this mutation.We report a Chinese Han family with one individual affected with HVDRR.A homozygous missense mutation c.122G4A(p.C41Y) in the VDR gene was found to be responsible for the patient's syndrome.In contrast to the results of treatment of HVDRR in other patients,our patient responded well to a supplement of oral calcium and a low dose of calcitriol. | Qianqian Pang Xuan Qi Yan Jiang Ou Wang Mei Li Xiaoping Xing Jin Dong Weibo Xia | 2016 | Bone Research2016，4，1： | 9 |
| 18 | Lipid layer thickness and tear meniscus height measurements for the differential diagnosis of evaporative dry eye subtypes显示文摘AIM: To explore a new diagnostic index for differentiating the evaporative dry eye(EDE) subtypes by analysis of their respective clinical characteristics. METHODS: A cross-sectional study of 139 patients(139 eyes) with EDE who were enrolled and classified as obstructive meibomian gland dysfunction(MGD)(n=81) and non-obstructive MGD(n=58) EDE. All patients completed a Standard Patient Evaluation of Eye Dryness(SPEED) questionnaire and were evaluated for average lipid layer thickness(LLT), tear meniscus height measurements(TMH), tear break-up time(TBUT), ocular surface staining score, Schirmer I test(SIT), lid margin abnormalities, and meibomian gland function and morphology. RESULTS: Age, average LLT, TMH, scores of lid margin abnormalities, meibum quality, meibomian gland loss(MGL)(all P≤0.001), and TBUT(P=0.03) were all significantly different between obstructive MGD EDE patients and nonobstructive MGD EDE patients. Average LLT in obstructive MGD EDE was correlated with meibomian expressibility(r=-0.541, P≤0.001), lid margin abnormalities were marginally not significant(r=0.197, P=0.077), and TMH was correlated with MGL(total MGL: r=0.552, P≤0.001; upper MGL: r=0.438, P≤0.001; lower MGL: r=0.407, P≤0.001). Average LLT in non-obstructive MGD EDE, was correlated with meibomian expressibility and Oxford staining(r=-0.396, P=0.002; r=-0.461, P≤0.001). The efficiency of combining average LLT and TMH was optimal, with a sensitivity of 80.2% and a specificity of 74.1%. Obstructive MGD EDE patients had an average LLT≥69 nm and TMH≥0.25 mm, while non-obstructive MGD EDE patients had an average LLT<69 nm and TMH<0.25 mm.CONCLUSION: Obstructive MGD EDE and nonobstructive MGD EDE have significantly different clinical characteristics. Combining average LLT and TMH measurements enhanced their reliability for differentiating these two subtypes and provided guidance for offering more precise treatments for EDE subtypes. | Xuan Sang Yan Li Liu Yang Jia-Hui Liu Xiao-Ran Wang Chao-Yang Li Ying Liu Chen-Jie Wang Xiong-Jun He Shou-Bi Wang Zhi-Chong Wang | 2018 | International Journal of Ophthalmology(English edition)2018，11，9： | 9 |
| 19 | Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells显示文摘Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16^(INK4A)(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option. | Wenjia Liu Liqiang Zhang Kun Xuan Chenghu Hu Shiyu Liu Li Liao Bei Li Fang Jin Songtao Shi Yan Jin | 2018 | Bone Research2018，6，4： | 9 |
| 20 | Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats显示文摘 | Shan-shan SHAO Yuan-fei ZHAO Yong-feng SONG Chao XU Jian-mei YANG Shi-meng XUAN Hui-li YAN Chun-xiao YU Meng ZHAO Jin XU Jia-jun ZHAO | 2014 | Acta Pharmacologica Sinica2014，35，11： | 9 |
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