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| 1 | Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing,China显示文摘Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease(COVID-19)and the evidence of person-to-person transmission.Limited data are available for asymptomatic infections.This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers.Epidemiological investigations were conducted among all close contacts of COVID-19 patients(or suspected patients)in Nanjing,Jiangsu Province,China,from Jan 28 to Feb 9,2020,both in clinic and in community.Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples.Their clinical records,laboratory assessments,and chest CT scans were reviewed.As a result,none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening.Five cases(20.8%)developed symptoms(fever,cough,fatigue,etc.)during hospitalization.Twelve(50.0%)cases showed typical CT images of ground-glass chest and 5(20.8%)presented stripe shadowing in the lungs.The remaining 7(29.2%)cases showed normal CT image and had no symptoms during hospitalization.These 7 cases were younger(median age:14.0 years;P=0.012)than the rest.None of the 24 cases developed severe COVID-19 pneumonia or died.The median communicable period,defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests,was 9.5 days(up to 21 days among the 24 asymptomatic cases).Through epidemiological investigation,we observed a typical asymptomatic transmission to the cohabiting family members,which even caused severe COVID-19 pneumonia.Overall,the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization.However,the communicable period could be up to three weeks and the communicated patients could develop severe illness.These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests.Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged. | Zhiliang Hu Ci Song Chuanjun Xu Guangfu Jin Yaling Chen Xin Xu Hongxia Ma Wei Chen Yuan Lin Yishan Zheng Jianming Wang Zhibin Hu Yongxiang Yi Hongbing Shen | 2020 | Science China(Life Sciences)2020，63，5： | 77 |
| 2 | Strontium and boron isotopic constraint on the marine origin of the Khammuane potash deposits in southeastern Laos显示文摘Since 2006,we have conducted a geological exploration of the Khammuane area in southeastern Laos.Several thick sequences of potash deposits containing sylvite and carnallite were discovered from drilling Paleocene strata of the Thangon Formation(E1tg).To constrain the origin of the brine that formed thick sequences of salt mineral deposits,we measured the strontium and boron isotope composition of some salt minerals in the potash deposit.Boron isotope composition of halite-and potash-associated minerals in the Khammuane potash deposit varied from 19.91%to 31.01‰,which differs significantly from continental evaporates(-6.83‰--5.79‰)but is very close to that of salts precipitated from evapo-concentrated seawater(10‰-36‰).The 87Sr/86Sr ratios(0.707542 to 0.709461)of salts were also close to the values of Paleocene seawater(0.70772 to 0.707830).The content of Br-(0.01%-0.25%)and Br×103/Cl ratios(0.10-0.52)of halite were>10 times higher than that of common continental salts.These characteristics indicate clearly that the Laos potash deposits were deposited from seawater.The small variation in boron and strontium isotopes in all salt sedimentary sequences(gypsum-halite-potash-halite)also suggests that the recharge source should be stable and the effects of other continental water mixing are negligible.Large-scale potash deposits are commonly precipitated from seawater.Hence,the results of recent regional drilling work and geochemical research suggest extensive potash resources could occur in the Thangon Formation of southeastern Laos. | TAN HongBing MA HaiZhou LI BinKai ZHANG XiYing XIAO YingKai | 2010 | Chinese Science Bulletin2010，55，27： | 37 |
| 3 | Matrine reduces the proliferation and invasion of colorectal cancer cells via reducing the activity of p38 signaling pathway显示文摘Matrine 被使用了在反煽动性并且反癌症治疗很长时间。然而,在 colorectal 癌症(CRC ) 的反变形的效果和相关机制仍然是不清楚的。在这研究,我们调查了 matrine 的管理是否能经由调整表明小径的 p38 禁止人的 CRC 房间的增长,活动性,和侵略。结果证明 matrine 在 vitro 并且在 vivo 禁止了 CRC 房间的移植和侵略。在为 24 h 与 matrine 被对待以后,另外,表示在 CRC 房间矩阵 metalloproteinase-2 (MMP-2 ) 和 MMP-9 以及朊酶活动铺平以一种剂量依赖者方式被减少。而且, matrine 显然减少了 p38 的 phosphorylation 水平。有 p38 禁止者(SB203580 ) 和 matrine 的联合治疗在 CRC 房间导致了侵略以及 MMP-2/-9 表示的 synergistic 减小。matrine 在 vivo 禁止了 CRC 肿瘤的增长和转移,这也被发现。在结论, p38 发信号小径可以由减少 MMP-2/-9 的表示在 CRC 房间的移植和侵略上在 matrine 的禁止的效果包含,建议 matrine 可以是为 CRC 的一个潜在的治疗学的代理人。 | Hongtao Ren Shuqun Zhang Hongbing Ma Yali Wang Di Liu Xijing Wang Zhongwei Wang | 2014 | Acta Biochimica et Biophysica Sinica2014，46，12： | 16 |
| 4 | Avian influenza A virus H5N1 causes autophagy-mediated cell death through suppression of mTOR signaling显示文摘穿过种类障碍感染人的很少鸟的流行性感冒病毒,高度病原的流行性感冒 A (H5N1 ) 紧张夺走生活多于感染的病人的一半。与由 H5N1 感染的肺损害的大部分未知的机制,尖锐呼吸悲痛症候群(ARDS ) 是在牺牲品之中的死亡的主要原因。这里我们在场 H5N1 通过 mTOR 的抑制引起了 autophagic 房间死亡的事实发信号。由 autophagy 基因 Beclin1 的弄空或由 autophagy 禁止者 3-methyladenine (3 麻省) , autophagy 的抑制显著地减少了 H5N1 调停的房间死亡。我们建议 autophagic 房间死亡可以在 H5N1 流行性感冒病人贡献 ARDS 的发展, autophagy 的抑制能因此为 H5N1 感染的治疗成为新奇策略。 | Jianhui Ma Qian Sun Ruifang Mi Hongbing Zhang | 2011 | Journal of Genetics and Genomics2011，38，11： | 13 |
| 5 | Typical Geochemical Elements in Loess Deposit in the Northeastern Tibetan Plateau and Its Paleoclimatic Implication显示文摘Widespread and thick loess deposit in the northeastern Tibetan Plateau records paleoclimatic changes over the Quaternary period. In this study, we investigate a loess section located in a high terrace of the Huangshui River in the Xining Basin, and collect samples at 20-cm intervals by digging a well of 16-m depth (including paleosol S1 and S0 and several loess interlayers over the last glacial-interglacial cycle and the Holocene). Concentration of some active elements (Sr and Ca) and inert elements (Rb, Zr, Ti) in these loess samples are measured. The results show that ratios of those elements (oxide), such as Rb/Sr, Ti/Sr, and Zr/CaO ratios, would indicate sensitively paleoclimatic changes, especially the history of precipitation over the last glacial-interglacial and the Holocene. Moreover, the curves of Rb/Sr, Ti/Sr, and Zr/CaO ratios had almost the same variable trends from the bottom to the top and also closely correlated with values of magnetic susceptibility and the global marine δ18O record. But compared with the curves of magnetic susceptibility, the changes of ratios of these elements (oxide) are clearer and easy to understand. Therefore, the ratios of these typical chemical elements in the loess deposit may be used as an excellent index to investigate the history of paleoclimate, particularly precipitation changes in the northeastern Tibetan Plateau. | TAN Hongbing MA Haizhou ZHANG Xiying LU Huayu WANG Jianguo | 2006 | Acta Geologica Sinica(English Edition)2006，80，1： | 10 |
| 6 | Origin and evolution of oilfield brines from Tertiary strata in western Qaidam Basin:Constraints from ^(87)Sr/^(86)Sr,δD,δ^(18)O,δ^(34)S and water chemistry显示文摘Chemistry of major and minor elements,87Sr/86Sr,δD,δ18O and δ34S of brines were measured from Tertiary strata and Quaternary salt lakes in the western Qaidam Basin.The water chemistry data show that all oilfield brines are CaCl2 type.They were enriched in Ca2+,B3+,Li+,Sr2+,Br-,and were depleted in Mg2+,SO42-,which indicated that these brines had the characteristics of deeply circulated water.The relationship between δD and δ18O shows that all data of these brines decline towards the Global Meteoric Water Line(GWL) and Qaidam Meteoric Water Line(QWL),and that the intersection between oilfield brines and Meteoric Water Lines was close to the local spring and fresh water in the piedmont in the western Qaidam Basin.The results suggest that oilfield brines has initially originated from meteoric water,and then might be affected by water-rock metamorphose,because most oilfield brines distribute in the range of metamorphosing water.The 87Sr/86Sr values of most oilfield brines range from 0.71121 to 0.71194,and was less than that in salt lake water(>0.712),but close to that of halite in the study area.These imply that salt dissolution occurred in the process of migration.In addition,all oilfield brines have obviously much positive δ34S values(ranging from 26.46‰ to 54.57‰) than that of salt lake brines,which was caused by bacterial sulfate reduction resulting in positive shift of δ34S value and depleteed SO42-in oilfield brines.Combined with water chemical data and δD,δ18O,87Sr/86Sr,δ34S values,we concluded that oilfield brines mainly originate from the deeply circulated meteoric waters,and then are affected by salt dissolution,water-rock metamorphose,sulfate reduction and dolomitization during the process of migration.These processes alter the chemical compositions of oilfield brines and accumulate rich elements(such as B,Li,Sr,Br,K and so on) for sustainable utilization of salt lake resources in the Qaidam Basin. | FAN Qishun MA Haizhou LAI Zhongping TAN Hongbing LI Tingwei | 2010 | Chinese Journal Of Geochemistry2010，29，4： | 10 |
| 7 | Genetic Polymorphisms in the Precursor MicroRNA Flanking Region and Non-Small Cell Lung Cancer Survival显示文摘 | Hu, Zhibin Shu, Yongqian Chen, Yijiang Chen, Jiaping Dong, Jing Liu, Yao Pan, Shiyang Xu, Lin Xu, Jing Wang, Yi Dai , Juncheng Ma, Hongxia Jin, Guangfu Shen,Hongbing | 2011 | 南京医科大学学报(自然科学版)2011，31，6： | 8 |
| 8 | One-step generation of myostatin gene knockout sheep via the CRISPR/Cas9 system显示文摘The CRISPR/Cas(clustered regularly interspaced short palindromic repeats/CRISPR-associated)adaptive immune system,which was discovered in bacteria and archaea,can specifically degrade invasive viral and plasmid DNA by base pairing between crRNAs(CRISPR RNAs)and the target DNA[1,2].Recently,the Streptococcus pyogenes type II CRISPR system was shown to be able to perform efficient targeted gene disruption by employing three fundamental components:(1)Cas9 endonuclease. | Hongbing HAN Yonghe MA Tao WANG Ling LIAN Xiuzhi TIAN Rui HU Shoulong DENG Kongpan LI Feng WANG Ning LI Guoshi LIU Yaofeng ZHAO Zhengxing LIAN | 2014 | Frontiers of Agricultural Science and Engineering2014，1，1： | 8 |
| 9 | Prognostic assessment of apoptotic gene polymorphisms in non-small cell lung cancer in Chinese显示文摘Apoptosis plays a key role in inhibiting tumor growth, progression and resistance to anti-tumor therapy. We hypothesized that genetic variants in apoptotic genes may affect the prognosis of lung cancer. To test this hypothesis, we selected 38 potentially functional single nucleotide polymorphisms (SNPs) from 12 genes (BAX, BCL2, BID, CASP3, CASP6, CASP7, CASP8, CASP9, CASP10, FAS, FASLG and MCL1) involved in apoptosis to assess their prognostic significance in lung cancer in a Chinese case cohort with 568 non-small cell lung cancer (NSCLC) patients. Thirty-five SNPs passing quality control underwent association analyses, 11 of which were shown to be significantly associated with NSCLC survival (P<0.05). After Cox stepwise regression analyses, 3 SNPs were independently associated with the outcome of NSCLC (BID rs8190315: P=0.003; CASP9 rs4645981: P=0.007 and FAS rs1800682: P=0.016). A favorable survival of NSCLC was significantly associated with the genotypes of BID rs8190315 AG/GG (adjusted HR=0.65, 95% CI: 0.49-0.88), CASP9 rs4645981 AA (HR=0.22, 95% CI: 0.07-0.69) and FAS rs1800682 GG (adjusted HR=0.67, 95% CI: 0.46-0.97). Time-dependent receptor operation curve (ROC) analysis revealed that the area under curve (AUC) at year 5 was significantly increased from 0.762 to 0.819 after adding the risk score of these 3 SNPs to the clinical risk score. The remaining 32 SNPs were not significantly associated with NSCLC prognosis after adjustment for these 3 SNPs. These findings indicate that BID rs8190315, CASP9 rs4645981 and FAS rs1800682 polymorphisms in the apoptotic pathway may be involved in the prognosis of NSCLC in the Chinese population. | Songyu Cao Cheng Wang Xinen Huang Juncheng Dai Lingmin Hu Yao Liu Jiaping Chen Hongxia Ma Guangfu Jin Zhibin Hu Lin Xu Hongbing Shen | 2013 | The Journal of Biomedical Research2013，27，3： | 6 |
| 10 | Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial显示文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting. | Yuankai Shi Kaijian Lei Yuming Jia Bingqiang Ni Zhiyong He Minghong Bi Xicheng Wang Jianhua Shi Ming Zhou Qian Sun Guolei Wang Dongji Chen Yongqian Shu Lianke Liu Zhongliang Guo Yong Liu Junquan Yang Ke Wang Ke Xiao LinWu Tienan Yi Debin Sun Mafei Kang Tianjiang Ma Yimin Mao Jinsheng Shi Tiegang Tang Yan Wang Puyuan Xing Dongqing Lv Wangjun Liao Zhiguo Luo Bin Wang Xiaohong Wu Xiaoli Zhu Shuhua Han Qisen Guo Rongyu Liu Zhiwei Lu Jianyong Zhang Jian Fang Changlu Hu Yinghua Ji Guolong Liu Hong Lu Dedong Wu Junhong Zhang Shuyang Zhu Zheng Liu Wensheng Qiu Feng Ye Yan Yu Yanqiu Zhao Qinhong Zheng Jun Chen Zhanyu Pan Yiping Zhang Wenjuan Lian Bo Jiang Bo Qiu Guojun Zhang Hua Zhang Yanju Chen Yuan Chen Hongbing Duan Manxiang Li Shengming Liu Lijun Ma Hongming Pan Xia Yuan Xueli Yuan Yulong Zheng Emei Gao Li Zhao Shumin Wang Can Wu | 2021 | Cancer Communications2021，41，9： | 5 |
| 11 | U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population显示文摘在由维持 chromosomal 正直并且阻止染色体的生物变老的一个关键角色结束的 Telomeres 玩熔化。流行病学的研究建议了 telomere 长度的内部个人的差别能影响倾向到多重癌症,但是关于食道的有鳞的房间癌(ESCC ) 的证据仍然是不明确的。几 telomere 在白种人的长度相关的单个核苷酸多型性(TLSNP ) 在染色体宽的协会研究被报导了。然而,在 ESCC 开发的 telomere 长度和 TL-SNPs 的效果是不清楚的。因此,我们进行了盒子控制研究(1045 个 ESCC 案例和 1433 控制) 在中国人口评估在 telomere 长度, TL-SNPs,和 ESCC 风险之间的协会。作为结果, ESCC 案例显示出全面更短的相对 telomere 长度(RTL )( 中部:1.34 ) 比控制(中部:1.50, P < 0.001 ) 。更有趣地,一个明显的非线性的U字形的协会在 RTL 和 ESCC 风险之间被观察( P < 0.001 )与比率(95%信心间隔)等于到 2.40 的机会( 1.843.14 ), 1.36 ( 1.031.79 ), 1.01 ( 0.761.35 ),并且 1.37 ( 1.031.82 )为个人在第一(最短),第二,第三,并且 第5 (最长) quintile 分别地,在是的 第4 quintile 与那些相比引用组。没有重要协会在八报导 TL-SNPs 和 ESCC 危险性之间被观察。这些调查结果建议短或极其长的 telomeres 可以是为在中国人口的 ESCC 的风险因素。 | Jiangbo Du Wenjie Xue Yong Ji Xun Zhu Yayun Gu Meng Zhu Cheng Wang Yong Gao Juncheng Dai Hongxia Ma Yue Jiang Jiaping Chen Zhibin Hu Guangfu Jin Hongbing Shen | 2015 | Frontiers of Medicine2015，9，4： | 4 |
| 12 | Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma显示文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. | Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen | 2021 | Frontiers of Medicine2021，15，2： | 3 |
| 13 | 单周多西他赛加顺铂联合三维适形放疗治疗局部晚期食管癌的临床研究(英文)显示文摘Objective: This randomized controlled clinical study was to assess and compare the efficacy and safety of two chemoradiotherapy regimens [cisplatin+5-fluorouracil+3 dimensional conformal radiation therapy (3DCRT) and cisplatin+weekly docetaxel+3DCRT] in patients with locally advanced esophageal squamous cell carcinoma. Methods: A total of seventy-four patients with clinical stages IIB to IIIB esophageal squamous cell carcinoma were enrolled. Chemotherapy for PF group comprised 5-fluorouracil at days 1-5 (250 mg/m2/d) and cisplatin (20 mg/m2) at days 1-3 of every 28-day cycle; full treatment course included 2 cycles. Chemotherapy for DP group comprised docetaxel (20 mg/m2) and cisplatin (20 mg/m2) at days 1, 8, 15, 22, 29, and 36. Both groups treated with concurrent 60 Gy 3DCRT at 200 cGy/d. Results: Seventy-four patients were enrolled and 71 completed the planned treatment, with a follow-up rate of 95.94%. Short-term curative effect was not statistically significant between the two groups (P=0.471). The 2-year survival rates were 65.7% and 61.1%, respectively (P=0.806), 5 years survival rates were 34.29% and 27.78%, respectively (P=0.221), and there was no significant difference by Fisher test (P=0.734). As common side effects, incidence rates of radioactive esophagitis and hematological toxicity were lower in DP group. Conclusion: For locally advanced esophageal cancer patients, current chemoradiotherapy with chemotherapy regimen of weekly docetaxel plus cisplatin has equal curative effect with 5-fluorouracil plus cisplatin, but well-tolerated by reducing side effects such as radioactive esophagitis and bone marrow suppression. | Minghua Bai Baofeng Wang Xijing Wang Hongbing Ma Yali Wang Zhongwei Wang | 2013 | The Chinese-German Journal of Clinical Oncology2013，12，8： | 3 |
| 14 | Efficacy of combined inhibition of mTOR and ERK/MAPK pathways in treating a tuberous sclerosis complex cell model显示文摘Tuberous sclerosis complex (TSC) is an autosomal dominant tumor syndrome which afflicts multiple organs and for which there is no cure, such that TSC patients may develop severe mental retardation and succumb to renal or respiratory failure. TSC derives from inactivating mutations of either the TSC1 or TSC2 tumor suppressor gene, and the resulting inactivation of the TSC1/TSC2 protein complex causes hyperactivation of the mammalian target of rapamycin (mTOR), leading to uncontrolled cell growth and proliferation. Recent clinical trials of targeted suppression of mTOR have yielded only modest success in TSC patients. It was proposed that abrogation of a newly identified mTOR-mediated negative feedback regulation on extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway and on the well-documented RTK-PI3K-AKT signaling cascade could limit the efficacy of mTOR inhibitors in the treatment of TSC patients. Therefore, we speculate that dual inhibition of mTOR and ERK/MAPK pathways may overcome the disadvantage of single agent therapies and boost the efficacy of mTOR targeted therapies for TSC patients. Investigation of this hypothesis in a TSC cell model revealed that mTOR suppression with an mTOR inhibitor, rapamycin (sirolimus), led to up-regulation of ERK/MAPK signaling in mouse Tsc2 knockout cells and that this augmented signaling was attenuated by concurrent administration of a MEK1/2 inhibitor, PD98059. When compared with monotherapy, combinatorial application of rapamycin and PD98059 had greater inhibitory effects on Tsc2 deficient cell proliferation, suggesting that combined suppression of mTOR and ERK/MAPK signaling pathways may have advantages over single mTOR inhibition in the treatment of TSC patients. | Ruifang Mi Jianhui Ma Dechang Zhang Limin Li Hongbing Zhang | 2009 | Journal of Genetics and Genomics2009，36，6： | 3 |
| 15 | 高能聚束微波热疗联合沙培林胸腔注射治疗恶性胸水(英文)显示文摘Objective:The aim of the study was to evaluate the efficacy and toxicity of high power focused-beam microwave hyperthermia with intrapleural injection of Shapeilin for patients with malignant hydrothorax.Methods:Fifty-eight patients with malignant hydrothorax were divided into group A and group B randomly.All patients underwent indwelling pleural catheter and were treated by intrapleural injection of Shapeilin once three days.Treatment was composed of 3 times injection.Patients of group B received high power focused-beam microwave hyperthermia after injection of Shapeilin.Results:The response rate of group B(79.3%) was higher than that of group A(48.3%)(P < 0.05).Incidence of main adverse reactions,associated with Shapeilin,of two groups including fever and thoracodynia were similar(P > 0.05).Patients of group B didn't encounter severe toxicities of microwave hyperthermia.Conclusion:High power focused-beam microwave hyperthermia combined with intrapleural injection of Shapeilin is effective and tolerable for patients with malignant hydrothorax. | Lingqin Song Jianjun He Xijing Wang Hongbing Ma Shuqun Zhang Zhijun Dai Baofeng Wang Xiaobin Ma | 2011 | The Chinese-German Journal of Clinical Oncology2011，10，2： | 2 |
| 16 | Polygenic risk scores:the future of cancer risk prediction,screening,and precision prevention显示文摘Genome-wide association studies(GWASs)have shown that the genetic architecture of cancers are highly polygenic and enabled researchers to identify genetic risk loci for cancers.The genetic variants associated with a cancer can be combined into a polygenic risk score(PRS),which captures part of an individual’s genetic susceptibility to cancer.Recently,PRSs have been widely used in cancer risk prediction and are shown to be capable of identifying groups of individuals who could benefit from the knowledge of their probabilistic susceptibility to cancer,which leads to an increased interest in understanding the potential utility of PRSs that might further refine the assessment and management of cancer risk.In this context,we provide an overview of the major discoveries from cancer GWASs.We then review the methodologies used for PRS construction,and describe steps for the development and evaluation of risk prediction models that include PRS and/or conventional risk factors.Potential utility of PRSs in cancer risk prediction,screening,and precision prevention are illustrated.Challenges and practical considerations relevant to the implementation of PRSs in health care settings are discussed. | Yuzhuo Wang Meng Zhu Hongxia Ma Hongbing Shen | 2021 | Medical Review2021，1，2： | 2 |
| 17 | Improved MPEG-4 High-Efficiency AAC With Variable-Length Soft-Decision Decoding of the Quantized Spectral Coefficients显示文摘MPEG-4 High-Efficiency Advanced Audio Coding (HE-AAC) is designed for low bit rate applications, such as audio streaming in mobile communications. The HE-AAC audio codec offers a better coding efficiency since variable-length codes (VLCs) are adopted. However, HE-AAC has originally been designed for storage and error-free transmission conditions. For the transmission over bit error-prone channels, error propagation is a serious problem for the VLCs. Therefore, a robust HE-AAC decoder is desired, especially for mobile communications. In contrast to traditional hard-decision decoding, utilizing bit-wise channel reliability information, softdecision (SD) decoding has been known to offer better audio quality. In HE-AAC, the global gain parameter is coded with fixedlength codes (FLCs), while the scale factors and quantized spectral coefficients are coded with VLCs. In this work, we apply FL/SD decoding to the global gain parameter, VL/SD decoding to the parameters scale factors and quantized spectral coefficients. Especially, in order to apply VL/SD decoding to the quantized spectral coefficients, a new modified trellis representation in VL/SD decoding is proposed. An improved HE-AAC performance is clearly observed, with the support of both instrumental measurements and a subjective listening test. | Sai Han Hongbing Ma Ping Zhang Tim Fingscheidt | 2019 | China Communications2019，16，10： | 2 |
| 18 | Association of microRNA polymorphisms with the risk of head and neck squamous cell carcinoma in a Chinese population:a case-control study显示文摘Background:MicroRNA(miRNA) polymorphisms may alter miRNA-related processes,and they likely contribute to cancer susceptibility.Various studies have investigated the associations between genetic variants in several key miRNAs and the risk of human cancers;however,few studies have focused on head and neck squamous cell carcinoma(HNSCC) risk.This study aimed to evaluate the associations between several key miRNA polymorphisms and HNSCC risk in a Chinese population.Methods:In this study,we genotyped five common single-nucleotide polymorphisms(SNPs) in several key miRNAs(miR-149 rs2292832,miR-146 a rs2910164,miR-605 rs2043556,miR-608 rs4919510,and miR-196a2 rs11614913) and evaluated the associations between these SNPs and HNSCC risk according to cancer site with a case-control study including 576 cases and 1552 controls,which were matched by age and sex in a Chinese population.Results:The results revealed that miR-605 rs2043556[dominant model:adjusted odds ratio(OR) 0.71,95%confidence interval(CI) 0.58-0.88;additive model:adjusted OR 0.74,95%CI 0.62-0.89]and miR-196a2 rs11614913(dominant model:adjusted OR 1.36,95%C11.08-1.72;additive model:adjusted OR 1.28,95%C11.10-1.48) were significantly associated with the risk of oral squamous cell carcinoma(OSCC).Furthermore,when these two loci were evaluated together based on the number of putative risk alleles(rs2043556 A and rs11614913 G),a significant locus-dosage effect was noted on the risk of OSCC(P_(trend) < 0.001).However,no significant association was detected between the other three SNPs(miR-149 rs2292832,miR- 146 a rs2910164,and miR-608 rs4919510) and HNSCC risk.Conclusion:Our study provided the evidence that miR-605 rs2043556 and miR-196a2 rs11614913 may have an impact on genetic susceptibility to OSCC in Chinese population. | Limin Miao Lihua Wang Longbiao Zhu Jiangbo Du Xun Zhu Yuming Niu Ruixia Wang Zhibin Hu Ning Chen Hongbing Shen Hongxia Ma | 2016 | Chinese Journal of Cancer2016，35，11： | 2 |
| 19 | Association of assisted reproductive technology, germline de novo mutations and congenital heart defects in a prospective birth cohort study显示文摘Emerging evidence suggests that children conceived through assisted reproductive technology(ART)have a higher risk of congenital heart defects(CHDs)even when there is no family history.De novo mutation(DNM)is a well-known cause of sporadic congenital diseases;however,whether ART procedures increase the number of germline DNM(gDNM)has not yet been well studied.Here,we performed whole-genome sequencing of 1137 individuals from 160 families conceived through ART and 205 families conceived spontaneously.Children conceived via ART carried 4.59 more gDNMs than children conceived spontaneously,including 332 paternal and 1.26 maternal DNMs,after correcting for parental age at conception,cigarette smoking,alcohol drinking,and exercise behaviors.Paternal DNMs in offspring conceived via ART are characterized by C>T substitutions at CpG sites,which potentially affect protein-coding genes and are significantly associated with the increased risk of CHD.In addition,the accumulation of non-coding functional mutations was independently associated with CHD and 87.9% of the mutations were originated from the father.Among ART offspring,infertility of the father was associated with elevated paternal DNMs;usage of both recombinant and urinary follicle-stimulating hormone and high-dosage human chorionic gonadotropin trigger was associated with an increase of maternal DNMs.In sum,the increased gDNMs in offspring conceived by ART were primarily originated from fathers,indicating that ART itself may not be a major reason for the accumulation of gDNMs.Our findings emphasize the importance of evaluating the germline status of the fathers in families with the use of ART. | Cheng Wang Hong Lv Xiufeng Ling Hong Li Feiyang Diao Juncheng Dai Jiangbo Du Ting Chen Qi Xi Yang Zhao Kun Zhou Bo Xu Xiumei Han Xiaoyu Liu Meijuan Peng Congcong Chen Shiyao Tao Lei Huang Cong Liu Mingyang Wen Yangqian Jiang Tao Jiang Chuncheng Lu Wei Wu Di Wu Minjian Chen Yuan Lin Xuejiang Guo Ran Huo Jiayin Liu Hongxia Ma Guangfu Jin Yankai Xia Jiahao Sha Hongbing Shen Zhibin Hu | 2021 | Cell Research2021，31，8： | 2 |
| 20 | Comparison of dimension reduction-based logistic regression models for case-control genome-wide association study:principal components analysis vs.partial least squares显示文摘With recent advances in biotechnology, genome-wide association study(GWAS) has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression(LR) based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression(PC-LR), partial least squares-based logistic regression(PLS-LR), have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor?mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism(SNP) set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis.On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data. | Honggang Yi Hongmei Wo Yang Zhao Ruyang Zhang Junchen Dai Guangfu Jin Hongxia Ma Tangchun Wu Zhibin Hu Dongxin Lin Hongbing Shen Feng Chen | 2015 | The Journal of Biomedical Research2015，29，4： | 2 |
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