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| 1 | Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion显示文摘The recent outbreak of coronavirus disease(COVID-19)caused by SARS-CoV-2 infection in Wuhan,China has posed a serious threat to global public health.To develop specific anti-coronavirus therapeutics and prophylactics,the molecular mechanism that underlies viral infection must first be defined.Therefore,we herein established a SARS-CoV-2 spike(S)protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV.We solved the X-ray crystal structure of six-helical bundle(6-HB)core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain.We previously developed a pan-coronavirus fusion inhibitor,EK1,which targeted the HR!domain and could inhibit infection by divergent human coronaviruses tested,including SARS-CoV and MERS-CoV.Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM,about 241-and 149-fold more potent than the original EK1 peptide,respectively.EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested,including SARS-CoV and MERS-CoV,as well as SARSr-CoVs,and potently inhibited the replication of 5 live human coronaviruses examined,including SARS-CoV-2.Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection,suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs. | Shuai Xia Meiqin Liu Chao Wang Wei Xu Qiaoshuai Lan Siliang Feng Feifei Qi Linlin Bao Lanying Du Shuwen Liu Chuan Qin Fei Sun Zhengli Shi Yun Zhu Shibo Jiang Lu Lu | 2020 | Cell Research2020，30，4： | 81 |
| 2 | A complete sequence and comparative analysis of a SARS-associated virus(Isolate BJ01)显示文摘The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs. We report the complete genome sequence and comparative analysis of an isolate (BJ01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS- associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymous mutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to beinvolved in the immunoreactions between the virus and its host. Two amino acid changes have been detected in the Mprotein, which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides noevidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of otherpossible SARS-related pathogen(s). | QIN E'de ZHU Qingyu YU Man FAN Baochang CHANG Guohui SI Bingyin YANG Bao PENG Wenming JIANG Tao LIU Bohua DENG Yongqiang LIU Hong ZHANG Yu WANG Cui LI Yuquan GAN Yonghua LI Xiaoyu L Fushuang TAN Gang CAO Wuchun, YANG Ruifu Institute of Microbiology and Epidemiology, Chinese Academy of Military Medical Sciences, Beijing 100071, China WANG Jian, LI Wei, XU Zuyuan, LI Yan, WU Qingfa, LIN Wei, CHEN Weijun, TANG Lin, DENG Yajun, HAN Yujun, LI Changfeng, LEI Meng, LI Guoqing, LI Wenjie, L Hong, SHI Jianping, TONG Zongzhong, ZHANG Feng, LI Songgang, LIU Bin, LIU Siqi, DONG Wei, WANG Jun, Gane K-S Wong, YU Jun & YANG Huanming* Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300 National Center for Genome Information, Beijing 101300, China | 2003 | Chinese Science Bulletin2003，48，10： | 121 |
| 3 | Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21^(WAF1) expression and hepatic apoptosis显示文摘AIM To detect the expression of caspase 3gene in primary human hepatocellular carcinoma(HCC)and investigate its relationship to p21WAF1gene expression and HCC apoptosis.METHODS In situ hybridization was employedto determine caspase 3 and p21WAF1expression inHCC.In situ end-labeling was used to detecthepatocytic apoptosis in HCC.RESULTS Twenty-one of 39(53.8%)cases ofHCC were found to express caspase 3transcripts,while 45.2% of HCC failed toexpress caspase 3.Non-cancerous adjacent livertissues showed more positive caspase 3(87.5%,7/8)as compared with HCC(P<0.05).The expression of caspase 3 is correlated withHCC differentiation,72.2%(13/18)ofmoderately to highly differentiated HCC showedcaspase 3 transcripts positive,while only 38.1%of poorly differentiated HCC harbored caspase 3transcripts(P<0.05).No relationship wasfound between caspase 3 expression and tumorsize or grade or metastasis,although 52.5%(5/8)of HCC with metastasis were caspase 3positive and a little higher than that with nometastasis(51.6%,P>0.05).Expression of caspase 3 alone did not affect the apoptosisindex(AI)of HCC.The AI was 7.12%o in caspase3-positive tumors(n=21),while in caspase 3-negative cases(n=18)6.59%0(P>0.05).Expression of caspase 3 clearly segregated withp21WAF1positive tumors as compared withp21WAF1-negative cases(16 of 23,69.6% versus5 of 16,31.3%)with statistical significance(P=0.017).In the cases with positive caspase 3and negative p21WAF1,the Al was found slightlyhigher,but with no statistical significance,thanthat with expression of p21WAF1and caspase 3(7.21‰ vs 6.98‰,P>0.05).CONCLUSION Loss of caspase 3 expressionmay contribute to HCC carcinogenesis,althoughthe expression of caspase 3 does not correlatewell with cell apoptosis in HCC.p21WAF1may bemerely one of the inhibitors which can reducecaspase 3 mediated cell apoptosis in HCCs. | Bao Hua Sun Jun Zhang Bao JǜWang Xi Ping Zhao You Kun Wang Zhi Qun Yu Dong Liang Yang Lian Jie Hao Department of Clinical Immunology,Tongji Hospital,Tongji Medical University,Wuhan 430030,Hubei Province,China | 2000 | World Journal of Gastroenterology2000，6，3： | 65 |
| 4 | H7N9 virulent mutants detected in chickens in China pose an increased threat to humans显示文摘 | Jianzhong Shi Guohua Deng Huihui Kong Chunyang Gu Shujie Ma Xin Yin Xianying Zeng Pengfei Cui Yan Chen Huanliang Yang Xiaopeng Wan Xiurong Wang Liling Liu Pucheng Chen Yongping Jiang Jinxiong Liu Yuntao Guan Yasuo Suzuki Mei Li Zhiyuan Qu Lizheng Guan Jinkai Zang Wenli Gu Shuyu Han Yangming Song Yuzhen Hu Zeng Wang Linlin Gu Wenyu Yang Libin Liang Hongmei Bao Guobin Tian Yanbing Li Chuanling Qiao Li Jiang Chengjun Li Zhigao Bu Hualan Chen | 2017 | Cell Research2017，27，12： | 70 |
| 5 | Moxibustion inhibits interleukin-12 and tumor necrosis factor alpha and modulates intestinal flora in rat with ulcerative colitis显示文摘AIM: To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS: A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS: HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are associated with an inflamed colon, were significantly lower in the HPM and SA groups than in the model group (0.244 ± 0.107, 0.628 ± 0.257 vs 1.691 ± 0.683, P < 0.01 for E. coli, and 0.351 ± 0.181, 0.416 ± 0.329 vs 1.285 ± 1.039, P < 0.01 for B. fragilis). The expression of TNF-α and IL-12 was decreased after HPM and SA treatment as compared to UC model alone (4970.81 ± 959.78, 6635.45 ± 1135.16 vs 12333.81 ± 680.79, P < 0.01 for TNF-α, and 5528.75 ± 1245.72, 7477.38 ± 1259.16 vs 12550.29 ± 1973.30, P < 0.01 for IL-12). CONCLUSION: HPM treatment can regulate intestinal flora and inhibit the expression of TNF-α and IL-12 in the colon tissues of UC rats, indicating that HPM can improve colonic immune response. | Xiao-Mei Wang Yuan Lu Lu-Yi Wu Shu-Guang Yu Bai-Xiao Zhao Hong-Yi Hu Huan-Gan Wu Chun-Hui Bao Hui-Rong Liu Jin-Hai Wang Yi Yao Xue-Gui Hua Hui-Ying Guo Li-Rong Shen | 2012 | World Journal of Gastroenterology2012，18，46： | 57 |
| 6 | An insoluble polysaccharide from the sclerotium of Poria cocos improves hyperglycemia, hyperlipidemia and hepatic steatosis in ob/ob mice via modulation of gut microbiota显示文摘Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide(WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a(1-3)-β-D-glucan with an average Mw of 4.486 × 10~6 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16 S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism. | SUN Shan-Shan WANG Kai MA Ke BAO Li LIU Hong-Wei | 2019 | Chinese Journal of Natural Medicines2019，17，1： | 60 |
| 7 | Fast-track rehabilitation program vs conventional care after colorectal resection:A randomized clinical trial显示文摘AIM:To compare the fast-track rehabilitation program and conventional care for patients after resection of colorectal cancer.METHODS:One hundred and six consecutive patients who underwent fast-track rehabilitation program were encouraged to have early oral feeding and movement for early discharge,while 104 consecutive patients underwent conventional care after resection of colorectal cancer.Their gastrointestinal functions,postoperative complications and hospital stay time were recorded.RESULTS:The restoration time of gastrointestinal functions in the patients was significantly faster after fasttrack rehabilitation program than after conventional care(2.1 d vs 3.2 d,P < 0.01).The percentage of patients who developed complications was significantly lower 30 d after fast-track rehabilitation program than after conventional care(13.2% vs 26.9%,P < 0.05).Also,the percentage of patients who had general complications was significantly lower 30 d after fast-track rehabilitation program than after conventional care(6.6% vs 15.4%,P < 0.05).The postoperative hospital stay time of the patients was shorter after fast-track rehabilitation program than after conventional care(5 d vs 7 d,P < 0.01).No significant difference was observed in the readmission rate 30 d after fast-track rehabilitation program and conventional care(3.8% vs 8.7%).CONCLUSION:The fast-track rehabilitation program can significantly decrease the complications and shorten the time of postoperative hospital stay of patients after resection colorectal cancer. | Gang Wang Zhi-Wei Jiang Jing Xu Jian-Feng Gong Yang Bao Li-Fei Xie Jie-Shou Li | 2011 | World Journal of Gastroenterology2011，17，5： | 43 |
| 8 | Effect of hepatitis C virus infection on expression of several cancer-associated gene products in hepatocellular carcinoma显示文摘NTRODUCTIONOurpreviousstudiesbyseroepidemiological,molecularepidemiologicalandimmunopathologicalmethodshaverevealedthathepa... | YANG Jian Min, WANG Rong Quan, BU Bao Guo, ZHOU Zi Cheng, FANG Dian Chun and LUO Yuan Hui | 1999 | World Journal of Gastroenterology1999，5，1： | 42 |
| 9 | Moxibustion treatment modulates the gut microbiota and immune function in a dextran sulphate sodium-induced colitis rat model显示文摘AIM To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis.METHODS A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls(HC), ulcerative colitis model group(UC), UC with 7 d of moxibustion(UC-7), UC with 14 d of moxibustion(UC-14), UC with mesalazine gavage(UC-W), HC with 7 d of moxibustion(HC-7), HC with 14 d of moxibustion(HC-14). Moxibustion was applied to the bilateral Tianshu(ST25). Gut microbiome profiling was conducted by 16 S r RNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively. RESULTS Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term(7 d) but no longer term(14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12(IL-12)(P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, Ig A, tumour necrosis factor-α and its receptors 1(TNFR1) and TNFR2(P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10(P < 0.01) and transforming growth factor-β(P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion.CONCLUSION Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucosal tissue damage and modulating the gut microbiome and intestinal mucosal immunity. | Qin Qi Ya-Nan Liu Xiao-Ming Jin Lin-Shuang Zhang Cun Wang Chun-Hui Bao Hui-Rong Liu Huan-Gan Wu Xiao-Mei Wang | 2018 | World Journal of Gastroenterology2018，24，28： | 42 |
| 10 | Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome显示文摘BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1β,IL-18,and resistance-like moleculeβby promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD(ASC)and cysteinyl-aspartate-specific proteinase 1(Caspase-1).The relative DNA abundances of Lactobacillus,Bifidobacteria,Faecalibacterium prausnitzii,and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6,ASC,and Caspase-1 in the colon.CONCLUSION These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling. | Chun-Hui Bao Chun-Ye Wang Guo-Na Li Yi-Lu Yan Di Wang Xiao-Ming Jin Lu-Yi Wu Hui-Rong Liu Xiao-Mei Wang Zheng Shi Huan-Gan Wu | 2019 | World Journal of Gastroenterology2019，25，32： | 45 |
| 11 | New vacuum solar telescope and observations with high resolution显示文摘The New Vacuum Solar Telescope(NVST) is a one meter vacuum solar telescope that aims to observe fine structures on the Sun. The main goals of NVST are high resolution imaging and spectral observations, including measurements of the solar magnetic field. NVST is the primary ground-based facility used by the Chinese solar research community in this solar cycle. It is located by Fuxian Lake in southwest China, where the seeing is good enough to perform high resolution observations. We first introduce the general conditions at the Fuxian Solar Observatory and the primary science cases of NVST. Then, the basic structures of this telescope and instruments are described in detail. Finally, some typical high resolution data of the solar photosphere and chromosphere are also shown. | Zhong Liu Jun Xu Bo-Zhong Gu Sen Wang Jian-Qi You Long-Xiang Shen Ru-Wei Lu Zhen-Yu Jin Lin-Fei Chen Ke Lou Zhi Li Guang-Qian Liu Zhi Xu Chang-Hui Rao Qi-Qian Hu Ru-Feng Li Hao-Wen Fu Feng Wang Men-Xian Bao Ming-Chan Wu Bo-Rong Zhang | 2014 | Research in Astronomy and Astrophysics2014，14，6： | 37 |
| 12 | The Genome Sequence Archive Family: Toward Explosive Data Growth and Diverse Data Types显示文摘The Genome Sequence Archive(GSA)is a data repository for archiving raw sequence data,which provides data storage and sharing services for worldwide scientific communities.Considering explosive data growth with diverse data types,here we present the GSA family by expanding into a set of resources for raw data archive with different purposes,namely,GSA(http://gffzz77e3413bc06540eds0coxkk9bco6x6onk.ffgz.tsg.suse.edu.cn/gsa/),GSA for Human(GSA-Human,http://gffzz77e3413bc06540eds0coxkk9bco6x6onk.ffgz.tsg.suse.edu.cn/gsa-human/),and Open Archive for Miscellaneous Data(OMIX,http://gffzz77e3413bc06540eds0coxkk9bco6x6onk.ffgz.tsg.suse.edu.cn/omix/).Compared with the 2017 version,GSA has been significantly updated in data model,online functionalities,and web interfaces.GSA-Human,as a new partner of GSA,is a data repository specialized in human genetics-related data with controlled access and security.OMIX,as a critical complement to the two resources mentioned above,is an open archive for miscellaneous data.Together,all these resources form a family of resources dedicated to archiving explosive data with diverse types,accepting data submissions from all over the world,and providing free open access to all publicly available data in support of worldwide research activities. | Tingting Chen Xu Chen Sisi Zhang Junwei Zhu Bixia Tang Anke Wang Lili Dong Zhewen Zhang Caixia Yu Yanling Sun Lianjiang Chi Huanxin Chen Shuang Zhai Yubin Sun Li Lan Xin Zhang Jingfa Xiao Yiming Bao Yanqing Wang Zhang Zhang Wenming Zhao | 2021 | Genomics, Proteomics & Bioinformatics2021，19，4： | 38 |
| 13 | Prevalence and evolution of drug resistance HIV-1 variants in Henan, China显示文摘To understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug nave AIDS patients, 118 AIDS patients who received three months antiretroviral therapy and 124 AIDS patients who received six months antiretroviral treatment were recruited in the southern part of Henan province. Information on general condition, antiretroviral medicines, adherence and clinical syndromes were collected by face to face interview. Meanwhile, 14ml EDTA anticoagulant blood was drawn. CD4/CD8 T cell count, viral load and genotypic drug resistance were tested. The rates of clinical improvement were 55.1% and 50.8% respectively three months and six months after antiretroviral therapy. The mean CD4 cell count after antiretroviral therapy was significantly higher than in drug nave patients. The prevalence rate of drug resistant HIV strains were 13. 9%, 45.4% and 62.7% in drug nave patients, three month treatment patients and six month treatment patients, respectively. The number of resistance mutation codons and the frequency of mutations increased significantly with continued antiretroviral therapy. The mutation sites were primarily at the 103, 106 and 215 codons in the three-month treatment group and they increased to 15 codon mutations in the six-month treatment group. From this result, the evolution of drug resistant strains was inferred to begin with the high level NNRTI resistant strain, and then develop low level resistant strains to NRTIs. The HIV strains with high level resistance to NVP and low level resistance to AZT and DDI were highly prevalent because of the AZT+DDI+NVP combination therapy. These HIV strains were also cross resistant to DLV, EFV, DDC and D4T. Poor adherence to therapy was believed to be the main reason for the emergence and prevalence of drug resistant HIV strains. The prevalence of drug resistant HIV strains was increased with the continu- ation of antiretroviral therapy in the southern part of Henan province. Measures, that could promote high level adherence, provide new drugs and change ART regimens in failing patients, should be implemented as soon as possible. | Jing Yun LI Han Ping LI Lin LI Hong LI Zhe WANG Kun YANG Zuo Yi BAO Dao Min ZHUANG Si Yang LIU Yong Jian LIU Hui XING Yi Ming SHAO | 2005 | Cell Research2005，15，11： | 34 |
| 14 | Relationship between the level of fasting plasma glucose and beta cell functions in Chinese with or without diabetes显示文摘背景类型 2 糖尿病是贝它房间 functions.However 的进步损失描绘的长期的疾病,贝它房间功能的评估为试图阐明的临床的 practice.We 昂贵或不方便在胰岛素应答和 fasting 血浆葡萄糖( FPG )的变化之间的协会早为 analysis.The 在有正常的血葡萄糖或多糖症的 1192 个中国个人全部的 diabetes.Methods A 的发展期间被注册 insulinogenic | PANG Can BAO Yu-qian WANG Chen LU Jun-xi JIA Wei-ping XIANG Kun-san | 2008 | Chinese Medical Journal2008，，21： | 34 |
| 15 | Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors显示文摘在 enucleated 鸡蛋的体的房间的 Reprogramming 做了多丽,绵羊,在 1996 的第一个成功地克隆的哺乳动物。然而,绵羊的机制体的房间 reprogramming 还没被探讨了。而且,绵羊胚胎的茎(ES ) 细胞仍然不是可得到的,它限制精确修改基因的绵羊的产生。在这研究,我们报导体的房间能是的那只绵羊直接 reprogrammed 到导致的 pluripotent 用定义因素(Oct4, Sox2, c-Myc, Klf4, Nanog, Lin28, SV40 大 T 和 hTERT ) 的茎(iPS ) 房间。我们的观察显示从绵羊的体的细胞比从另外的种,在 iPS,细胞被报导了的体的细胞对改编更困难。我们证明绵羊 iPS 房间表示 ES 房间标记,包括碱的磷酸酶, Oct4, Nanog, Sox2, Rex1,阶段特定的胚胎的 antigen-1, TRA-1-60, TRA-1-81 和 E-cadherin。绵羊 iPS 房间展出了正常 karyotypes 并且能在 vitro 并且在 teratomas 区分进所有三细菌层。我们的学习可以帮助在绵羊揭示体的房间 reprogramming 的机制并且提供一个平台为绵羊 ES 房间探索文化条件。而且,绵羊 iPS 房间可以直接被用来产生精确修改基因的绵羊。 | Lei Bao Lixiazi He Jijun Chen Zhao Wu Jing Liao Lmgdun Rao Jiangtao Ren Hui Li Hui Zhu Lei Qian Yijun Gu Huimin Dai Xun Xu Jinqiu Zhou Wen Wang Chun Cui Lei Xiao | 2011 | Cell Research2011，21，4： | 32 |
| 16 | Immunostaining of PD-1/PD-Ls in liver tissues of patients with hepatitis and hepatocellular carcinoma显示文摘AIM: To investigate the expression of programmed death (PD)-1,PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).METHODS: Liver biopsies and HCC specimens from patients were collected and histologically examined.The expression of PD-1,PD-L1,and PD-L2 in biopsy specimens of chronic hepatitis and HCC specimens was evaluated by immunohistochemical staining.The association between the expression level of PD-1,PD-L1,and PD-L2 and clinical and pathological variables was analyzed statistically.RESULTS: Expression of PD-1 was found in liverinfiltrating lymphocytes.In contrast,PD-L1 and PD-L2 were expressed in non-parenchyma liver cells and tumor cells.The expression of PD-L1 was significantly correlated with hepatitis B virus infection (1.42 ± 1.165 vs 0.50 ± 0.756,P = 0.047) and with the stage of HCC (7.50 ± 2.121 vs 1.75 ± 1.500 vs 3.00 ± 0.001,P = 0.018).PD-1 and PD-Ls were significantly up-regulated in HCC specimens (1.40 ± 1.536 vs 5.71 ± 4.051,P = 0.000;1.05 ± 1.099 vs 4.29 ± 3.885,P = 0.004;1.80 ± 1.473 vs 3.81 ± 3.400,P = 0.020).CONCLUSION: PD-L1 may contribute to negative regulation of the immune response in chronic hepatitis B.PD-1 and PD-Ls may play a role in immune evasion of tumors. | Bao-Ju Wang Jun-Jie Bao Jun-ZhongWang Yang Wang Min Jiang Ming-You Xing Wan-Guang Zhang Jun-Ying Qi Michael Roggendorf Meng-Ji Lu Dong-Liang Yang | 2011 | World Journal of Gastroenterology2011，17，28： | 32 |
| 17 | LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration显示文摘新兴的研究在少些在染色质水平,但是相对调整基因表示记录长非编码的 RNA (LncRNAs ) 的角色被知道他们怎么调整 DNA methylation。这里,我们识别 lncRNA, Dum (发展联系 pluripotency 2 (Dppa2 ) 在上游的有约束力的肌肉 lncRNA ) 在骨胳的 myoblast 房间。Dum 的表示动态地在 vitro 并且在 vivo 在 myogenesis 期间被调整。它被在 myoblast 区别之上有约束力的 MyoD transcriptionally 也导致。功能的分析证明它支持 myoblast 区别和导致损坏的肌肉新生。机械学地, Dum 被发现它的附近的基因到沉默, Dppa2,在通过招募的 cis Dnmt1, Dnmt3a 和 Dnmt3b。而且, intrachromosomal 在 Dum 地点和 Dppa2 倡导者之间循环为 Dum/Dppa2 相互作用是必要的。一起,我们识别了与 Dnmts 交往调整 myogenesis 的新奇 lncRNA。 | Lijun Wang Yu Zhao Xichen Bao Xihua Zhu Yvonne Ka-yin Kwok Kun Sun Xiaona Chen Yongheng Huang Ralf Jauch Miguel A Esteban Hao Sun Huating Wang | 2015 | Cell Research2015，25，3： | 34 |
| 18 | Research on preservation and enrichment mechanisms of organic matter in muddy sediment and mudstone显示文摘Using multidiscipline methodologies, the differences in preservation and enrichment mechanisms of organic matter (OM) in muddy sediment and mudstone are investigated. In clay fractions, concentra- tions of TOC and chloroform bitumen “A” are significantly higher than those in coarser fractions. This indicates that clay minerals (CM) play an important role in enriching OM. The content of chloroform bitumen “A” increases obviously in the clay fraction, which reveals that dissolvable OM is the main composition of coalesce with clay minerals. Furthermore, TG and DTA data show that OM enrichment mechanisms and preservation forms have multiplicity. Several exothermic peaks in the DTA curves demonstrate that muddy sediment and mudstone contain a number of bioclasts and amorphous OM besides dissolvable OM. Through analyzing with XRD and DTA after mudstone samples were pretreated, the conclusions can be arrived at. Firstly, CM interlayer space of XRD curves and exothermic peaks of DTA curves both change as temperature increases. Secondly, the changes of CM interlayer space and exothermic peaks are concordant and stable around 350℃. All these are the features that OM enters CM interlayers to form stable organo-clay complexes. Therefore, the combination format of OM with CM is not only surface adsorption, partial OM enters CM interlayers to form stable organo-clay complexes. Finally, through the research on OM preservation forms and enrichment mechanisms in muddy sedi- ment and mudstone, the hydrocarbon-generation processes and the global carbon cycle and budget can be explained. | CAI JinGong BAO YuJin YANG ShouYe WANG XingXin FAN DaiDu XU JinLi WANG AiPing | 2007 | Science China Earth Sciences2007，50，5： | 25 |
| 19 | Adakite-type sodium-rich rocks in Awulale Mountain of west Tianshan:Significance for the vertical growth of continental crust显示文摘The sodium-rich dacites and albite porphyries of Permian in the Awulale Mountain of west Tianshan have unique chemical and trace element signatures identical to adakite. These intermediate-acidic igneous rocks are characterized by high Na2O, Al2O3 and Sr contents and high Sr/Y and La/Y ratios (>40 and >20, respectively), and low Y and Yb contents, and strong depletion in HREE, and positive Eu anomaly. The (143Nd/144Nd)i is in the range from0.51236 to 0.51248 and the εNd(t) is positive value (+0.79-+3.11); the (87Sr/86Sr)i is in the range from 0.7052 to 0.7054. These Nd and Sr isotopic composition features indicate that the source rocks of these adakite-type rocks are from a weakly depleted mantle, or a depleted mantle, but was contaminated by the crustal materials. These adakite-type rocks were most likely derived from the partial melting of new underplated basaltic rocks under the conditions of amphibo-lite to eclogite transition in the postcollisional environment of North Xinjiang during the Permian | XIONG Xiaolin ZHAO Zhenhua BAI Zhenghua MEI Houjun WANG Yixian WANG Qiang XU Jifeng Niu Hecai BAO Zhiwei | 2001 | Chinese Science Bulletin2001，46，10： | 25 |
| 20 | Monolayer Graphene as a Saturable Absorber in a Mode-Locked Laser显示文摘我们证明单层 graphene 的内在的性质允许它当时,为锁模式的纤维激光充当一个更有效的可饱和的吸收器与多层的 graphene 相比。单层 graphene 的吸收能与多层的 graphene,有像皱纹的缺点的 graphene,或 functionalized graphene 相比在更低的刺激紧张被浸透。单层 graphene 有 65.9% 的显著地大的调整深度,而多层的 graphene 的调整深度极大地由于 nonsaturable 吸收被减少并且散布损失。微微秒 ultrafast 激光脉搏(1.23 ps ) 能作为一个可饱和的吸收器用单层 graphene 被产生。由于 ultrafast 松驰时间,更大的调整深度和单层 graphene 的更低的散布损失,它以塑造能力,脉搏稳定性,和产量精力的脉搏比多层的 graphene 更好表现。 | Qiaoliang Bao Han Zhang Zhenhua Ni Yu Wang Lakshminarayana Polavarapu Zexiang Shen Qing-Hua Xu Dingyuan Tang Kian Ping Loh | 2011 | Nano Research2011，4，3： | 25 |
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