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| 1 | CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys显示文摘Dear Editor,PINK1 mutations cause autosomal recessive and early-onset Parkinson’s disease(PD)with selective neurodegeneration.Unfortunately,current PINK1 knockout(KO)mouse1,2 and pig models3,4 are unable to recapitulate the selective and overt neurodegeneration seen in PD patients.Furthermore,endogenous Pink1 in the mouse brain is expressed at very low levels and can only be detected via immunoprecipitation,5 meaning that PINK1’s function in the mammalian brain needs to be assessed using larger animals that are closer to humans.We previously used CRISPR/Cas9 to target the monkey gene in one-cell stage embryos.6 Using the same approach,we designed two gRNAs to target exon 2(T1)and exon 4(T2),which encode a kinase domain in the PINK1 gene of rhesus monkeys(Fig.1a).CRISPR/Cas9 and PINK1 gRNAs were injected into one-cell stage rhesus monkey embryos.A T7E1 assay and sequencing of PCR products from the injected embryos showed high efficiency(61.5%)in targeting PINK1(Fig.1b and Supplementary information,Fig.S1).Transfer of 87 embryos to 28 surrogate rhesus monkeys resulted in 11 pregnancies(39.2%)(Fig.1b).Eleven fetuses developed to term and were born naturally.Of these live monkeys,eight carried PINK1 mutations(M),and three were wild type(WT).However,three mutant monkeys(M1,M3 and M4)were newborn triplets that struggled to survive and died 3-4 days after birth.One WT newborn monkey also died after a difficult labor.Another mutant monkey(M2)died 7 days after birth without noticeable warning signs or symptoms.The other three mutant monkeys(M6,M7 and M8)have lived for three years;M5,however,reduced its food intake and showed weakness at the age of 1.5 years,and died 30 days after anesthesia for MRI examination. | Weili Yang Yunbo Liu Zhuchi Tu Chong Xiao Sen Yan Xishan Ma Xiangyu Guo Xiusheng Chen Peng Yin Zhengyi Yang Su Yang Tianzi Jiang Shihua Li Chuan Qin Xiao-Jiang Li | 2019 | Cell Research2019，29，4： | 12 |
| 2 | Interpretation of breast cancer screening guideline for Chinese women显示文摘Breast cancer is the most common malignant tumor in Chinese women.Early screening is the best way to improve the rates of early diagnosis and survival of breast cancer patients.The peak onset age for breast cancer in Chinese women is considerably younger than those in European and American women.It is imperative to develop breast cancer screening guideline that is suitable for Chinese women.By summarizing the current evidence on breast cancer screening in Chinese women,and referring to the latest guidelines and consensus on breast cancer screening in Europe,the United States,and East Asia,the China Anti-Cancer Association and National Clinical Research Center for Cancer(Tianjin Medical University Cancer Institute and Hospital)have formulated population-based guideline for breast cancer screening in Chinese women.The guideline provides recommendations on breast cancer screening for Chinese women at average or high risk of breast cancer according to the following three aspects:age of screening,screening methods,and screening interval.This article provides more detailed information to support the recommendations in this guideline and to provide more direction for current breast cancer screening practices in China. | Yubei Huang Zhongsheng Tong Kexin Chen Ying Wang Peifang Liu Lin Gu Juntian Liu Jinpu Yu Fengju Song Wenhua Zhao Yehui Shi Hui Li Huaiyuan Xiao Xishan Hao | 2019 | Cancer Biology & Medicine2019，16，4： | 10 |
| 3 | Crystal structure of the swine-origin A (H1N1)- 2009 influenza A virus hemagglutinin (HA) reveals similar antigenicity to that of the 1918 pandemic virus显示文摘Influenza virus is the causative agent of the seasonal and occasional pandemic flu.The current H1N1 influenza pandemic,announced by the WHO in June 2009,is highly contagious and responsible for global economic losses and fatalities.Although the H1N1 gene segments have three origins in terms of host species,the virus has been named swine-origin influenza virus(S-OIV)due to a predominant swine origin.2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many aspects.Hemagglutinin is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of infection.Primary sequence analysis of the 2009 S-OIV hemagglutinin(HA)reveals its closest relationship to that of the 1918 pandemic influenza virus,however,analysis at the structural level is necessary to critically assess the functional significance.In this report,we report the crystal structure of soluble hemagglutinin H1(09H1)at 2.9Å,illustrating that the 09H1 is very similar to the 1918 pandemic HA(18H1)in overall structure and the structural modules,including the five defined antiboby(Ab)-binding epitopes.Our results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV,and people born around the 1918 are resistant to the current pandemic,yet younger generations are more susceptible to the 2009 pandemic. | Wei Zhang Jianxun Qi Yi Shi Qing Li Feng Gao Yeping Sun Xishan Lu Qiong Lu Christopher J.Vavricka Di Liu Jinghua Yan George F.Gao | 2010 | Protein & Cell2010，1，5： | 10 |
| 4 | NEW DEVELOPMENT IN DOUBLE GLOW SURFACE ALLOYING TECHNOLOGY显示文摘Several kinds of special alloys are produced on the surfaces of iron and steels by using double glow surface alloying technology. Surface Ni-Cr-Mo-Nb alloy,surface precipitation hardening high speed steel and surface precipitation hardening stainless steel are introduced. | Xu Zhong Liu Xiaoping Li Zhonghou Research Institute of Surface Engineering, Taiyuan University of Technology, Taiyuan 030024, ChinaXie Xishan Zhang Xu University of Science and Technology Beijing | 2002 | Chinese Journal of Mechanical Engineering2002，15，2： | 5 |
| 5 | Microstructure-based hot extrusion process control principles for nickel-base superalloy pipes显示文摘The properties of nickel-base superalloy pipes are determined by microstructure, and the microstructure can be tuned by hot extrusion process. There are two major questions in hot extrusion: one is how to successfully extrude pipes without apparent defects, the other is how to make the microstructure under control. However, up to now, there is no systematical report about hot extrusion process and microstructure control for nickel-base superalloys. In present study, a series of technical control principles for hot extrusion are proposed basing on practical manufacture facts, large amounts of experimental studies and finite element simulation of several typical nickel-base superalloys. The common used technical control principles can be applied for hot extrusion parameters determination to maintain safety hot extrusion and microstructure control. In the investigation of microstructure control based hot extrusion principles, the action rules of different working parameters on hot extrusion field quantities were established. The upper and lower limits of different principles were obtained in consideration of materials characteristics and extruder conditions. The limitations were overlapped on the action rules to determine the optimized hot extrusion parameters. The microstructure-based control principle proposed in present work can provide theoretical guidance for hot extrusion parameter determination and optimization. | He Jiang Linhan Li Jianxin Dong Xishan Xie | 2018 | Progress in Natural Science:Materials International2018，28，3： | 4 |
| 6 | Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients显示文摘 | Lili Yang Baozhu Ren Hui Li Jinpu Yu Shui Cao Xishan Hao Xiubao Ren | 2013 | Cancer Immunology Immunotherapy2013，，1： | 2 |
| 7 | Low-Pressure Metamorphism of Granulite Facies in an Early Proterozoic Orogenic Event in Central Inner Mongolia显示文摘According to the kinds of feldspar and rock associations in the Ai-rich gneisses, the low-pressure metamorphic crust of the Early Proterozoic granulite facies in central Inner Mongolia can be divided into southern and northern belts which are composed of six rock associations. They represent the relevant rock sequences of the layered metamorphic rock series formed under specific metamorphic temperature and pressure conditions as well as tectonic environments. Mineral inclusions and reaction texture have recorded that the medium-temperature high-pressure mineral assemblages are replaced by the high-temperature low-pressure mineral assemblages, thus, giving rise to: garnet+quartz→ hypersthene+plagioclase; kyanite→sillimanite and garnet+kyanite/sillimanite+quartz→cordierite. The deformation fabrics of the rocks, the change of mineral assemblages and the PTt path of metamorphism indicate that the contempranceous high-temperature normal-slip ductile shearing is the main cause of the formation of the low-pressure metamorphic crust of granulite facies. In the orogenic event, the co-action of thrusting and extension resulted in the change of a medium-temperature high-pressure metamorphic environment into the high-temperature low-pressure metamorphic conditions. | Liu Xishan, Jin Wei and Li Shuxun Changchun University of Earth Sciences, Changchun, Jilin Sun Sheping | 1993 | Acta Geologica Sinica(English Edition)1993，67，1： | 2 |
| 8 | Autologous cytokine-induced killer cell immunotherapy in lung cancer: a phase II clinical study显示文摘 | Runmei Li Changli Wang Liang Liu Chunjuan Du Shui Cao Jinpu Yu Shizhen Emily Wang Xishan Hao Xiubao Ren Hui Li | 2012 | Cancer Immunology Immunotherapy2012，，11： | 2 |
| 9 | Multimarker Detection of MAGE-1,MAGE-3 and AFP mRNAs by a Real-time Quantitative PCR Assay:a Possible Predictor of Hematogenous Micrometastasis of Hepatocellular Carcinoma显示文摘OBJECTIVE To explore the relationship between multimarker detection of MAGE-1,MAGE-3 and AFP mRNAs in the peripheral blood of patients with hepatocellular carcinoma and micrometastasis using a realtime quantitative-PCR(real-time Q-PCR)assay. METHODS Peripheral blood samples were obtained from control subjects and 86 patients with hepatocellular carcinoma (HCC).Real-time Q-PCR was used to detect MAGE-1,MAGE-3, and AFP mRNAs in the blood cells. RESULTS In 86 tumor specimens,the positivity for MAGE-1, MAGE-3,and AFP genes was respectively 34.9%(30/86),60.5% (52/86)and 69.8%(60/86).All specimens expressed at least one marker.MAGE-1,MAGE-3,and AFP transcripts were detected respectively in 12(14.0%),18(20.1%)and 29(33.7%)of the 86 blood specimens from hepatocellular carcinoma patients,while 45 specimens(52.3%)were positive for at least one marker.In addition,MAGE-1,MAGE-3 and AFP gene transcripts were not detected in any peripheral blood specimens from 25 chronic liver disease patients and 28 normal healthy volunteers.The positive rate correlated with the TNM clinical stages,extrahepatic metastasis and portal vein carcinothrombosis(P<0.05).No correlation was found between tumor size,tumor number, differentiation,serum a-fetoprotein(AFP)and the positive rate. CONCLUSION Our results indicate that a multimarker real- time Q-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a hepatocyte-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients with better sensitivity and specificity. | Yuqing Zhang Qiang Li Ning Liu Tianqiang Song Rende Guo Lingxin Meng Xishan Hao | 2008 | Chinese Journal of Clinical Oncology2008，5，2： | 2 |
| 10 | Analysis of nonlinear characteristics for a three-phase, five-limb transformer under DC bias 显示文摘 | LI Xiaoping WEN Xishan MARKHAM P N | 2010 | Journal2010，25，4： | 1 |
| 11 | MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7显示文摘 | Qiang Li Chaoxia Zou Chendan Zou Zhongjing Han Haifeng Xiao Huiyan Wei Wei Wang Lei Zhang Xueying Zhang Qingchao Tang Chunjing Zhang Ji Tao Xishan Wang Xu Gao | 2013 | Cancer Letters2013，，： | 1 |
| 12 | Analysis ofnonlinear characteristics for a three-phase,five-limb transform-er under DC bias显示文摘 | Li Xiaoping Wen Xishan Markham Penn N | 2010 | IEEE Transactions On Power Delivery2010，25，4： | 1 |
| 13 | The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinalfluid can be useful indicators for diagnosis of meningeal carcinomatosis oflung cancer显示文摘 | Peng Wang Yingzhe Piao Xiaohui Zhang Wenliang Li Xishan Hao | 2013 | Cancer Biomarkers2013，，2： | 1 |
| 14 | Analysis of nonlinear characteristics for a three-phase,five-limb transformer under DC bias显示文摘 | Li Xiaoping Wen Xishan Markham P N | 2010 | IEEE Trans on Power Delivery2010，25，4： | 1 |
| 15 | MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7显示文摘 | Qiang Li Chaoxia Zou Chendan Zou Zhongjing Han Haifeng Xiao Huiyan Wei Wei Wang Lei Zhang Xueying Zhang Qingchao Tang Chunjing Zhang Ji Tao Xishan Wang Xu Gao | 2013 | Cancer Letters2013，，1： | 1 |
| 16 | Imaging beyond the diagnosis: image-guided enzyme/prodrug cancer therapy显示文摘理想的治疗将指向癌症房间当时 sparing 正常织物。然而,在很常规的化疗,正常房间和导致不幸的副作用的癌症房间被损坏。位于 enzyme/prodrug 治疗下面的原则是激活 prodrug 酶被交付或在肿瘤织物列在后面表示了无毒的 prodrug 哪个全身地被管理。当酶集中被检测在肿瘤织物高时,非侵略的成像形式能在指导 prodrug 管理充满一个重要壁龛但是在正常织物低。因此,有最小化的有毒的效果的高治疗学的功效能被期望。这评论在 enzyme/prodrug 癌症治疗介绍分子的成像的最近的开发。我们在监视酶交货 / 表示包括磁性的回声成像,位置排放断层摄影术和光成像集中于成像形式的申请,指导 prodrug 管理并且评估在 vivo 的即时治疗学的反应。 | Xinyi Tong Xishan Chen Cong Li | 2011 | Acta Biochimica et Biophysica Sinica2011，43，1： | 1 |
| 17 | Analysis of Lymph Node Metastases of 1,526 Cases with Thoracic Esophageal and Cardiac Carcinomas: A Random Sampling Report froni the Fourth Hospital of Hebei Medical University from 1996 to 2004显示文摘OBJECTIVE To summarize the regular pattern and state oflymph node metastasis of patients with esophageal and cardiaccarcinomas,so as to analyze factors influencing lymph nodemetastasis.METHODS Clinical data collected from 1,526 thoracicesophageal and cardiac carcinoma patients who were admitted inthe Fourth Hospital of Hebei Medical University during a periodfrom January 1996 to December 2004,were randomly selectedand an Access Database of the patient's information was set up.Eight clinico-pathologic factors,including the patient's age,tumorlocation and size,pathological classification,the depth of tumorinvasion,vascular tumor embolus (VTE),the state of surroundingorgan encroachment and the status of tumor residues,wereidentified.A correlation between these factors and metastases wasstatistically analyzed using SPSS13.0 software.RESULTS Lymph node metastatic sites from esophagealcarcinomas included the thoracic and abdominal cavity.Lymphnode metastasis from the superior esophageal carcinomasmainly occurred in the neck and thoracic cavity.There was atwo-way lymph node metastasis in the patients with the middleesophageal carcinoma.The inferior esophageal carcinomas mainlymetastasized to the paraesophageal,paragastric cardia,and leftgastric artery lymph nodes.The rate and degree of the metastasisfrom the inferior esophageal carcinomas were significantly highercompared to those of the superior and the middle esophagealcarcinomas (P<0.0125).The degree of abdominal lymph node metastasis fromcarcinomas of the gastric cardia was significantly higher comparedwith that of esophageal carcinomas.In the group with carcinomaof the gastric cardia,the rate and degree of the lymph nodemetastases in the paragastric cardia and left gastric artery weresignificantly higher compared to the group with esophagealcarcinoma (P<0.05).Paraesophageal lymph node metastasis fromcarcinomas of the gastric cardia in the thoracic cavity frequentlyoccurred,too,and the degree of the metastasis was similar to thatof esophageal carcinoma.There was no significant difference inthe rate and degree of the paraesophageal lymph-node metastasisbetween the group with carcinoma of the gastric cardia comparedto those with esophageal carcinoma (P>0.05).Multifactoriallogistic regression analysis showed that the tumor size,depth oftumor encroachment,VTE,and tumor residues could all bringabout obvious impact on lymph-node metastases (P<0.05).CONCLUSION Lymph node metastasis from superioresophageal carcinomas mainly occurs in the neck and thoraciccavity.The middle esophageal carcinomas presented a two-waylymph-node metastasis (both the upwards and the downwards),and the lymph node metastasis from inferior esophagealcarcinomas mainly occurred in the thoracic and abdominal cavities.The metastases of carcinoma of the gastriccardia were most commonly found in the abdominalcavity,with frequent paraesophageal lymph-nodemetastasis.The sufficient attention should be paidto neck lymph node clearance in cases of esophagealcarcinoma.What is of the greatest concern is theclearance of the left gastric artery lymph nodes,andalso in cases of gastric cardia carcinoma,clearance,the paraesophageal lymph nodes.With an increasein the tumor size and depth of tumor encroachment,and occurrence of VTE and tumor residual cells,therisk of lymph node metastasis is significantly raised (P<0.05). | Wei Liu Xishan Hao Yong Chen Haixin Li Shijie Wang Peizhong Wang Hng Jin Liyun Guan Qian Fan Linan Song Yumin Ping Xianli Meng Rui Wang Junfeng Liu Xiaoling Wang | 2008 | Chinese Journal of Clinical Oncology2008，5，6： | 1 |
| 18 | Long noncoding RNA HOTAIR involvement in cancer显示文摘 | Yansheng Wu Li Zhang Yang Wang Hui Li Xiubao Ren Feng Wei Wenwen Yu Xudong Wang Lun Zhang Jinpu Yu Xishan Hao | 2014 | Tumor Biology2014，，10： | 1 |
| 19 | Analysis of nonlinear characteristics for a three-phase, five-limb transformer under dc bias显示文摘 | Li Xiaoping Wen Xishan Markham PN | 2010 | IEEE Trans on Power Delivery2010，25，4： | 1 |
| 20 | Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients显示文摘 | Lili Yang Baozhu Ren Hui Li Jinpu Yu Shui Cao Xishan Hao Xiubao Ren | 2013 | Cancer Immunology, Immunotherapy2013，，1： | 1 |
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