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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 | Identification of a novel coronavirus causing severe pneumonia in human:a descriptive study显示文摘Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans. | Li-Li Ren Ye-Ming Wang Zhi-Qiang Wu Zi-Chun Xiang Li Guo Teng Xu Yong-Zhong Jiang Yan Xiong Yong-Jun Li Xing-Wang Li Hui Li Guo-Hui Fan Xiao-Ying Gu Yan Xiao Hong Gao Jiu-Yang Xu Fan Yang Xin-Ming Wang Chao Wu Lan Chen Yi-Wei Liu Bo Liu Jian Yang Xiao-Rui Wang Jie Dong Li Li Chao-Lin Huang Jian-Ping Zhao Yi Hu Zhen-Shun Cheng Un-Lin Liu Zhao-Hui Qian Chuan Qin Qi Jin Bin Cao Jian-Wei Wang | 2020 | Chinese Medical Journal2020，，9： | 99 |
| 3 | Prevalence of Autism Spectrum Disorder in China:A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years显示文摘This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children. | Hao Zhou Xiu Xu Weili Yan Xiaobing Zou Lijie Wu Xuerong Luo Tingyu Li Yi Huang Hongyan Guan Xiang Chen Meng Mao Kun Xia Lan Zhang Erzhen Li Xiaoling Ge Lili Zhang Chunpei Li Xudong Zhang Yuanfeng Zhou Ding Ding Andy Shih Eric Fombonne Yi Zheng Jisheng Han Zhongsheng Sun Yong-hui Jiang Yi Wang LATENT-NHC Study Team | 2020 | Neuroscience Bulletin2020，36，9： | 158 |
| 4 | Serum pepsinogen levels and their influencing factors:A population-based study in 6990 Chinese from North China显示文摘AIM: To explore the essential characteristics of serum pepsinogen (PG) levels in Chinese people, by analyzing the population-based data on the serum levels of PG Ⅰ and Ⅱ and the PGⅠ/Ⅱ ratio, and their influencing factors in Chinese from North China. METHODS: A total of 6990 subjects, who underwent a gastric cancer screening in North China from 1997 to 2002, were collected in this study. Serum pepsinogen levels were measured by enzyme-linked immunosorbent assay (ELISA). H pylori status was determined by histological examination and H pylori-IgG ELISA. The cut-off point was calculated by using receiving operator characteristics (ROC) curves. Factors linked to serum PG Ⅰ/Ⅱ ratio were identified using a multivariate logistic regression. RESULTS: The serum PGⅠ and PGⅡ levels were significantly higher in males than in females (95.2 μg/L vs 79.7 μg/L, P < 0.01; 12.1 μg/L vs 9.4 μg/L, P < 0.01), PGⅠ/Ⅱ ratio was significantly lower in males than in females (7.9 vs 8.3, P < 0.01). The PG Ⅰ/Ⅱ ratio decreased significantly in the aged groups following the progression of gastric mucosa from normal to non-atrophic and atrophic lesions (10.4, 8.8, and 6.6, respectively). The serum PGⅠand Ⅱ levels were significantly higher in patients with H pylori infection than in those without H pylori infection (88.7 μg/L vs 81.4 μg/L, P < 0.01; 11.4 μg/L vs 8.4 μg/L, P < 0.01), while the PGⅠ/Ⅱ ratio was significantly lower in patients with H pylori infection than in those without H pylori infection (7.7 vs 9.6, P < 0.01). For patients with atrophic lesions, the area under the PGⅠ/Ⅱ ROC curve was 0.622. The best cut-off point for PGⅠ/Ⅱ was 6.9, with a sensitivity of 53.2%, and a specificity of 67.5%. Factors linked to PGⅠ/Ⅱ were sensitive to identified PG using a multinomial logistic regression relying on the following inputs: males (OR: 1.151, 95% CI: 1.042-1.272, P = 0.006), age ≥ 61 years (OR: 1.358, 95% CI: 1.188-1.553, P = 0.000), atrophic lesion (OR: 2.075, 95% CI: 1.870-2.302, P = 0.000), and H pylori infection (OR: 1.546, 95% CI: 1.368-1.748, P = 0.000). CONCLUSION: The essential characteristics of serum PG levels in Chinese are significantly skewed from the normal distribution, and influenced by age, sex, gastric mucosa lesions and H pylori infection. PGⅠ/Ⅱ ratio is more suitable for identifying subgroups with different influence factors compared with PGⅠor PGⅡ alone. | Li-Ping Sun Yue-Hua Gong Lan Wang Yuan Yuan | 2007 | World Journal of Gastroenterology2007，13，48： | 52 |
| 5 | HIV prevalence and influencing factors analysis of sentinel surveillance among men who have sex with men in China, 2003-2011显示文摘 | WANG Lan WANG Lu Jessie L.Norris LI Dong-min GUO Wei DING Zheng-wei WANG Ning | 2012 | Chinese Medical Journal2012，，11： | 57 |
| 6 | Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210显示文摘Objective: SHR-1210 is a new and promising anti-PD-1 agent for solid tumors. During the phase I study of SHR-1210, we encountered a novel but prevalent immune-related dermatologic toxicity: reactive capillary hemangiomas(RCHs). Thus we tried to summarize the features of RCHs and estimate their relationship with tumor response.Methods: This prospective observational study systematically enrolled 98 patients with advanced solid tumors from April 27th,2016 to June 8th, 2017 in the context of the phase I clinical study of SHR-1210. This report focused on the skin toxicities. Patients underwent entire skin inspection every two weeks while taking medication. The clinical course of RCHs was recorded and their association with tumor response was estimated. The data cut-off date was November 15th, 2017.Results: After a median follow-up of 242(range, 29–567) days, RCHs were observed in 85.7%(84/98) of patients on cutaneous/mucosal surfaces; 84.5%(71/84) of the RCHs were evaluated as grade 1 adverse events. No grade 3 or 4 RCHs were observed. The time of onset of RCHs was dose dependent and shortest in the 400 mg-dose cohort(P < 0.001). Spontaneous and complete regression of RCHs was observed both during and after treatment. The objective response rate of tumors for patients with RCHs was 28.9%(24/83). However, no responders were observed among the patients without RCHs.Conclusions: RCHs were prevalent but manageable during treatment with SHR-1210. It might add to the expanding literature regarding immune-related dermatologic adverse events. | Xuelian Chen Lanying Ma Xi Wang Hongnan Mo Dawei Wu Bo Lan Dong Qu Hongtu Zhang Jing Huang Binghe Xu | 2019 | Cancer Biology & Medicine2019，16，1： | 53 |
| 7 | Apoptosis,proliferation and p53 gene expression of H.pylori associated gastric epithelial lesions显示文摘AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori.METHODS: DNEL technique and immunohistochemical technique were used to study the state of apoptosis,proliferation and p53 gene expression. A total of 100 gastric mucosal biopsy specimens, including 20 normal mucosa, 30H. Pylori-negative and 30 H. Pylorf-positive gastric precancerous lesions along with 20 gastric carcinomas were studied.RESULTS: There were several apoptotic cells in the superficial epithelium and a few proliferative cells within the neck of gastric glands, and no p53 protein expression in normal mucosa. In gastric carcinoma, there were few apoptotic cells, while there were a large number of proliferative cells, and expression of p53 protein significantly was increased. In the phase of metaplasia, the apoptotic index (Al, 4.36% ± 1.95%), proliferative index (PI, 19.11% ± 6.79%) and positivity of p53 expression (46.7%) in H. Pylori-positive group were higher than those in normal mucosa (P< 0.01). Al in H. Pylori-positive group was higher than that in H. Pylori-negative group (3.81% ±1.76%), PI in H. Pylori-positive group was higher than that in H. Pylori-negative group (12.25% ±5.63%, P<0.01 ). In the phase of dysplasia, Al (2.31% ± 1.10%) in H. Pylori-positive group was lower (3.05% ± 1.29%) than that in H. Pylori-negative group, but PI (33.89% ± 11.65%)wassignificantly higher(22.09± 8018%, P< 0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. Pylori-positive group, Als had an evidently graduall decreasing trend (P < 0.01 ), while Pis had an evidently gradual increasing trend (P< 0.05 or P< 0.01), and there was also a trend of gradual increase in the expression of p53 gene.CONCLUSION: In the course of the formation of gastric carcinoma, proliferation of gastric mucosa can be greatly increased by H. Pylori, and H. Pylori can induce apoptosis in the phase of metaplasia but in the phase of dysplasia H.pylori can inhibit cellular apoptosis. And H. Pylori infection can strengthen the expression of mutated p53 gene. | Zhong Zhang~1 Yuan Yuan Hua Gao Ming Dong Lan Wang Yue-Hua Gong 1 Department of Pathology,Shenyang Medical College,Shenyang 110031 Liaoning Province,China | 2001 | World Journal of Gastroenterology2001，7，6： | 46 |
| 8 | The Sunway TaihuLight supercomputer: system and applications显示文摘The Sunway Taihu Light supercomputer is the world's first system with a peak performance greater than 100 PFlops. In this paper, we provide a detailed introduction to the Taihu Light system. In contrast with other existing heterogeneous supercomputers, which include both CPU processors and PCIe-connected many-core accelerators(NVIDIA GPU or Intel Xeon Phi), the computing power of Taihu Light is provided by a homegrown many-core SW26010 CPU that includes both the management processing elements(MPEs)and computing processing elements(CPEs) in one chip. With 260 processing elements in one CPU, a single SW26010 provides a peak performance of over three TFlops. To alleviate the memory bandwidth bottleneck in most applications, each CPE comes with a scratch pad memory, which serves as a user-controlled cache. To support the parallelization of programs on the new many-core architecture, in addition to the basic C/C++and Fortran compilers, the system provides a customized Sunway Open ACC tool that supports the Open ACC2.0 syntax. This paper also reports our preliminary efforts on developing and optimizing applications on the Taihu Light system, focusing on key application domains, such as earth system modeling, ocean surface wave modeling, atomistic simulation, and phase-field simulation. | Haohuan FU Junfeng LIAO Jinzhe YANG Lanning WANG Zhenya SONG Xiaomeng HUANG Chao YANG Wei XUE Fangfang LIU Fangli QIAO Wei ZHAO Xunqiang YIN Chaofeng HOU Chenglong ZHANG Wei GE Jian ZHANG Yangang WANG Chunbo ZHOU Guangwen YANG | 2016 | Science China(Information Sciences)2016，59，7： | 45 |
| 9 | Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats显示文摘Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways. | Bin Lan Jin-wen Ge Shao-wu Cheng Xi-long Zheng Jun Liao Chao He Zheng-qing Rao Guo-zuo Wang | 2020 | Journal of Integrative Medicine2020，18，4： | 37 |
| 10 | Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma显示文摘Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756). | Bo Zhang Ling Qi Xi Wang Jianping Xu Yun Liu Lan Mu Xingyuan Wang Lidan Bai Jing Huang | 2020 | Cancer Communications2020，40，12： | 38 |
| 11 | 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://gffzz77e3413bc06540eds6owwbcc66fp569up.ffgz.tsg.suse.edu.cn/gsa/),GSA for Human(GSA-Human,http://gffzz77e3413bc06540eds6owwbcc66fp569up.ffgz.tsg.suse.edu.cn/gsa-human/),and Open Archive for Miscellaneous Data(OMIX,http://gffzz77e3413bc06540eds6owwbcc66fp569up.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 |
| 12 | Expression of gastric cancer-associated MG7 antigen in gastric cancer,precancerous lesions and H.pylori-associated gastric diseases显示文摘AIM: To investigate the relationship between the antigen MG7 antigen expression and gastric cancer as well as precancerous condition; to study the relationship between the MG7 antigen expression and H. pyloriinfection in benign gastric lesions in order to find out the effect of H. pylori infection on the process of gastric cancer development.METHODS: The level of MG7 antigen expression was determined by immunohistochemical method in 383 gastric biopsied materials. The intestinal metaplasia was determined by histochemistry method. The H. pyloriinfection was determined by HE stain, PCR and ELISA in 291 specimens, among which only 34 cases of H. pylori-associated gastric lesions were followed up.RESULTS: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric cancer increased gradually in ascending order (P<0.01). The positive rate of MG7 antigen expression in type Ⅲ intestinal metaplasia of gastric mucosa was higher than that of type Ⅰand Ⅱ intestinal metaplasia, being highly significant (P<0.05).The positive rate of MG7 antigen expression in superficial gastritis, atrophic gastritis and gastric cancer increased gradually (11.9 %, 64.8 %, 91.2 %, P<0.01). There was no significant difference between H.pylori-negative and H. pyloripositive intestinal metaplasia, atrophic gastritis and dysplasia of gastric epithelium in the positive rate of MG7 antigen expression. There was no expression of MG7 antigen in H. pylori-negative superficial gastritis. The positive rate of MG7 expression in H. pylori-positive superficial gastritis was 20.5 %, and the difference between them was significant (P<0.05). During following up, one of the three H. pylori negative cases turned positive again, and its MG7 antigen expression turned to be stronger correspondingly. 3 of 31 H. pyloripositive cases were detected as early gastric cancer, among which one with '+++' MG7 antigen expression was diminished after H. pylori eradication.CONCLUSION: MG7 antigen expression is highly specific in gastric cancer and can be used as a good marker for screening of gastric cancer; type Ⅲ intestinal metaplasia, atrophic gastritis and dysplasia should be followed up and MG7 antigen expression has high clinical value in the dynamic follow-up study; although the positive -MG7 in positiveH. pylorisuperficial gastritis show benign morphology in features, there is still the potential risk of developing into gastric cancer, hence special attention should be paid to those showing increasing MG7 antigen expression. | Dong-Li Guo Ming Dong Lan Wang Li-Ping Sun Yuan Yuan,Cancer Institute,First Affiliated Hospital,China Medical University,Shenyang,110001,Liaoning Province,China | 2002 | World Journal of Gastroenterology2002，8，6： | 37 |
| 13 | Helicobacter pylori infection generated gastric cancer through p53-Rb tumor-suppressor system mutation and telomerase reactivation显示文摘AIM: To investigate the relationship between Helicobacterpylori (H. pylori) infection and the expressions of the p53,Rb, c-myc, bcl-2 and hTERT mRNA in a series of diseasesfrom chronic gastritis (CG), intestinal metaplasia type Ⅰ or Ⅱ(IMⅠ-Ⅱ), intestinal metaplasia type Ⅲ (IMⅢ), mild or modestdysplasia (DysⅠ-Ⅱ), severe dysplasia (DysⅢ) to gastric cancer(GC) and to elucidate the mechanism of gastriccarcinogenesis relating to H.pyloriinfection.METHODS: 272 cases between 1998 and 2001 wereavailable for the study including 42 cases of CG, 46 cases ofIMⅠ-Ⅱ, 25 cases of IMⅢ, 48 cases of DysⅠ-Ⅱ, 27 cases ofDysⅢ, 84 cases of GC.-H. pyloriinfection and the expressionsof p53, Rb, c-myc, bcl-2 were detected by means ofstreptavidin-peroxidase (SP) immunohistochemical method.HTERT mRNA was detected byin situ hybridization(ISH).RESULTS: The expressions of p53, Rb, c-myc, hTERT mRNAand bcl-2 were higher in the GC than in CG, IN, Dys. Theexpression of c-myc was higher in IMⅢ with-H.pyloriinfection(10/16) than that without infection (1/9) and the positive ratein DysⅠ-Ⅱ and DysⅢ with-H.pyloriinfection was 18/30 and 13/17, respectively, higher than that without infection (4/18 and3/10, respectively). In our experiment mutated p53 had noassociation with H.pyloriinfection, theexpression of Rb wasassociated with-H. pyloriinfection in GC, but the p53-Rb tumor-suppressor system abnormal in DysⅠ-Ⅱ cases, DysⅢⅡ and GCcases with H. pyloriinfection was 21/30, 15/17 and 48/48respecively, higher than non-infection groups (4/18, 3/10, 28/36). Furthermore the level of hTERT mRNA in GC with H. pyloriinfection (47/48) was higher than that without infection (30/36), however the relationship between bcl-2 and H. pyloriwasonly in IMⅢ. C-myc had a close association with hTERT mRNAin DysⅢ and GC (P=0.0 253,0.0 305 respectively).CONCLUSION: In the gastric carcinogenesis, H. pylorimightcause the severe imbalance of proliferation and apoptosisin the precancerous lesions (IMⅢ and GysⅢ) first, leadingto p53-Rb tumor-suppressor system mutation and telomerasereactivation, and finally causes gastric cancer. | Jing Lan Yong-Yan Xiong Yi-Xian Lin Bi-Cheng Wang Ling-Ling Gong Hui-Sen Xu Guang-Song Guo Department of Pathology,Zhongnan Hospital,Wuhan University,Wuhan city 430071,Hubei Province,China | 2003 | World Journal of Gastroenterology2003，9，1： | 39 |
| 14 | ShRNA-mediated gene silencing of β-catenin inhibits growth of human colon cancer cells显示文摘AIM: To observe the gene silencing mediated by the specific shRNA targeted against β-catenin and its effect on cell proliferation and cycle distribution in the human colon cancer cell line Colo205. METHODS: Two shRNA plasmid vectors against β-catenin were constructed and transfected into Colo205 cells with LipofectamineTM2000. The down-regulations of β-catenin, c-myc and cyclinD1 expressions were detected by RT-PCR and western blot analysis. The cell proliferation inhibitions were determined by MTT assay and soft agar colony formation assay. The effect of these two β-catenin shRNAs on cell cycle distribution and apoptosis was examined by flow cytometry. RESULTS: These two shRNA vectors targeted against β-catenin efficiently suppressed the expression of β-catenin and its down stream genes, c-myc and cyclinD1. The expression inhibition rates were around 40%-50% either at the mRNA or at the protein level. The shRNA-mediated gene silencing of β-catenin resulted in significant inhibition of cell growth both on the culture plates and in the soft agar. Moreover, the cancer cells showed significant G0/G1 arrest and increased apoptosis at 72 h post transfection due to gene silencing. CONCLUSION: These specific shRNAs targeted against β-catenin could have a gene silencing effect and block the WNT signaling pathway. They could inhibit cell growth, increase apoptosis, and induce cell cycle arrest in Colo205 cells. ShRNA interference against β-catenin is of potential value in gene therapy of colon cancer. | Wen-Sheng Huang Jian-Ping Wang Ting Wang Jie-Yu Fang Ping Lan Jin-Ping Ma | 2007 | World Journal of Gastroenterology2007，13，48： | 33 |
| 15 | The combined effects of the ENSO and the Arctic Oscillation on the winter climate anomalies in East Asia显示文摘With the warm/cold phases of the El Ni o and Southern Oscillation (ENSO) as a background, the impacts of monthly variation in the Arctic Oscillation (AO) on the winter climate anomalies in East Asia are studied with the NCEP/DOE Reanalysis 2 data and the Chinese station data regarding temperature and rainfall. The combined effects of ENSO and the AO indicate that the winter climate anomalies are mainly influenced by the AO in northern China and the ENSO in southern China, when an El Ni o couples with a negative AO month or a La Ni a couples with a positive AO month. These climate anomalies in China are consistent with the mechanisms proposed in previous studies. However, most of China presents a different pattern of climate anomalies if an El Ni o couples with a positive AO month or a La Ni a couples with a negative AO month, with the exception of the temperature anomalies in northern China, which are still affected dominantly by the AO. Further analysis suggests that the causes are attributed to the differences in both the stratosphere-troposphere interaction and the extratropics-tropics interaction. In the former cases, zonal symmetric circulation prevails in the winter and the extratropics-tropics interaction is weakened. Thus, the influences of the ENSO and the AO on the East Asian climate mainly present linear combination effects. On the contrary, an annular mode of atmospheric circulation is not favored in the latter cases and the extratropics-tropics interaction is strong. Hence, the combined effects of the ENSO and the AO on the winter climate in East Asia present nonlinear characteristics. | CHEN Wen LAN XiaoQing WANG Lin MA Yin | 2013 | Chinese Science Bulletin2013，58，12： | 30 |
| 16 | New Classification of Herlyn-Werner-Wunderlich Syndrome显示文摘 | Lan Zhu Na Chen Jia-Li Tong Wei Wang LeiZhang Jing-He Lang | 2015 | Chinese Medical Journal2015，，2： | 30 |
| 17 | Micro-mechanical analysis of dynamic processes of nanomanipulation显示文摘In this study, atomic force microscope (AFM) tips are used as tools to cut and manipulate carbon nanotubes on various surfaces. The lateral forces acting on AFM tips during manipulation are also recorded and analyzed from the perspective of micro-mechanics. It is found that differences in surface conditions can lead to obvious increase in micro-friction between nanotube and substrate. And also due to rehybridization, carbon nanotubes present excellent resilience when undergoing different degrees of strain. Finally, carbon nanotubes can complexly deform from elastic stage to plastic stage before complete rupture. | HU Jie, ZHANG Yujun, LI Peng, WANG Hui, HUANG Lan & HU YuanzhongState Key Laboratory of Tribology, Tsinghua University, Beijing 100084, China Department of Physics, Tsinghua University, Beijing 100084, China College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China | 2004 | Science China(Physics,Mechanics & Astronomy)2004，47，z1： | 28 |
| 18 | Progress in China's Unconventional Oil & Gas Exploration and Development and Theoretical Technologies显示文摘The new century has witnessed a strategic breakthrough in unconventional oil & gas.Hydrocarbon accumulated in micro-/nano-scale pore throat shale systems has become an important domain that could replace current oil & gas resources.Unconventional oil & gas plays an increasingly important role in our energy demand.Tight gas,CBM,heavy oil and asphaltic sand have served as a key domain of exploration & development,with tight oil becoming a 'bright spot' domain and shale gas becoming a 'hotspot' domain.China has made great breakthroughs in unconventional oil & gas resources,such as tight gas,shale gas,tight oil and CBM,and great progress in oil shale,gas hydrate,heavy oil and oil sand.China has an estimated(223-263)×10~8t of unconventional oil resources and(890-1260)×l0^(12)m^3 of gas resources.China has made a breakthrough for progress in unconventional oil & gas study.New progress achieved in fine-grained sedimentary studies related to continental open lacustrine basin large-scale shallow-water delta sand bodies,lacustrine basin central sandy clastic flow sediments and marine-continental fine-grained sediments provide a theoretical basis for the formation and distribution of basin central reservoir bodies.Great breakthroughs have been made in unconventional reservoir geology in respect of research methodology & technology,multi-scale data merging and physical simulation of formation conditions.Overall characterization of unconventional reservoirs via multi-method and multi-scale becomes increasingly popular and facilitates the rapid development of unconventional oil & gas geological theory,method and technology.The formation of innovative,continuous hydrocarbon accumulation theory,the establishment of the framework of the unconventional oil & gas geological theory system,and the determination of the implications,geological feature,formation mechanism,distribution rule and core technology of unconventional oil& gas geological study lays a theoretical foundation for extensive unconventional oil & gas exploration and development.Theories and technologies of unconventional oil & gas exploration and development developed rapidly,including some key evaluation techniques such as 'sweet spot zone' integrated evaluation and a six-property evaluation technique that uses hydrocarbon source,lithology,physical property,brittleness,hydrocarbon potential and stress anisotropy,and some key development &engineering technologies including micro-seismic monitoring,horizontal drilling & completion and 'factory-like' operation pattern, 'man-made reservoir' development,which have facilitated the innovative development of unconventional oil & gas.These breakthroughs define a new understanding in four aspects:①theoretical innovation;② key technologies;③ complete market mechanism and national policy support;and ④ well-developed ground infrastructure,which are significant for prolonging the life cycle of petroleum industry,accelerating the upgrade and development of theories and technologies and altering the global traditional energy structure. | ZOU Caineng YANG Zhi ZHU Rukai ZHANG Guosheng HOU Lianhua WU Songtao TAO Shizhen YUAN Xuanjun DONG Dazhong WANG Yuman WANG Lan HUANG Jinliang WANG Shufang | 2015 | Acta Geologica Sinica(English Edition)2015，89，3： | 27 |
| 19 | Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress显示文摘癌症房间以他们的能力著名给新陈代谢的小径换新电线在各种各样的压力条件下面支持幸存和增长。尽管在肝生产了,酉同类身体没在正常的成年的肝房间被消费。我们这里发现酉同类分解代谢或 ketolysis 在 hepatocellular 被重新激活在营养剥夺条件下面的癌(HCC ) 房间。机械学地, 3-oxoacid CoA-transferase 1 (OXCT1 ) ,其表情在正常的成年的肝纸巾被压制的限制率的 ketolytic 酶,被浆液重新导致被触发饥饿的 mTORC2-AKT-SP1 在 HCC 房间发信号。而且,我们观察到在 HCC 的那提高的 ketolysis 为 AMPK 激活的压抑是批评的并且保护 HCC 房间免受过多的 autophagy 的伤害,从而提高肿瘤生长。重要地,临床的 HCC 样品的分析表明那增加的 OXCT1 表情预言更高耐心的死亡。一起拿,我们这里揭开剥夺营养的 HCC 房间为精力由采用酉同类身体的新奇新陈代谢的改编供应和癌症前进。 | De Huang Tingting Li Lin Wang Long Zhang Ronghui Yan Kui Li Songge Xing Gongwei Wu Lan Hu Weidong Jia Sheng-Cai Lin Chi V Dang Libing Song Ping Gao Huafeng Zhang | 2016 | Cell Research2016，26，10： | 27 |
| 20 | Transumbilical single-port laparoscopic cholecystectomy: a case report显示文摘 | GUO Wei ZHANG Zhong-tao HAN Wei LI Jian-she JIN Lan LIU Jun ZHAO Xiao-mu WANG Yu | 2008 | Chinese Medical Journal2008，，23： | 26 |
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