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| 1 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 2 | Is endoscopic ultrasound examination necessary in the management of esophageal cancer?显示文摘Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented. | Tomas DaVee Jaffer A Ajani Jeffrey H Lee | 2017 | World Journal of Gastroenterology2017，23，5： | 11 |
| 3 | Mechanosignaling activation of TGFβmaintains intervertebral disc homeostasis显示文摘Intervertebral disc(IVD) degeneration is the leading cause of disability with no disease-modifying treatment.IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal(NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin α_vβ_6-mediated activation of transforming growth factor beta(TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease(DDD). Knockout of TGFβ type II receptor(TβRII) or integrin α_v in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading.Administration of RGD peptide, TGFβ, and α_vβ_6-neutralizing antibodies attenuated IVD degeneration. Thus,integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD. | Qin Bian Lei Ma Amit Jain Janet L Crane Khaled Kebaish Mei Wan Zhengdong Zhang X Edward Guo Paul D Sponseller Cheryle A Seguin Lee H Riley Yongjun Wang Xu Cao | 2017 | Bone Research2017，5，1： | 9 |
| 4 | Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart显示文摘出生后的心通过 hypertrophic 生长适应应力和超载,可能病理学或有益的一个过程(生理的肥大) 。生理的肥大改进心脏的性能在健康并且 diseased 个人,然而,宣传这有利改编的机制仍然保持糟糕定义。我们识别 cytokine cardiotrophin (CT1 ) 1 作为能够包括导致的导出 cardiomyocyte 的 angiogenic 信号的心肌层,和刺激的短暂、可逆的肥大概括心的生理的生长的特色的一个因素增加了由脉管形成。CT1 的能力从 caspase 激活的调停 CK2 的制止发源导致生理的肥大,阻止到无限制的病理学的生长的转变。外长的 CT1 蛋白质交货稀释了病理并且在正确的心失败的一个严格的模型恢复了可收缩的功能,建议为这难处理的心脏病的一种新奇处理选择。 | Mohammad Abdul-Ghani Colin Suen Baohua Jiang Yupu Deng Jonathan J Weldrick Charis Putinski Steve Brunette Pasan Femando Tom T Lee Peter Flynn Frans H H Leenen Patrick G Burgon Duncan J Stewar Lynn A Megeney | 2017 | Cell Research2017，27，10： | 8 |
| 5 | Endoscopic management of esophageal cancer显示文摘Esophageal cancer(EC)generally consists of squamous cell carcinoma(which arise from squamous epithelium)and adenocarcinoma(which arise from columnar epithelium).Due to the increased recognition of risk factors associated with EC and the development of screening programs,there has been an increase in the diagnosis of early EC.Early EC is amenable to curative therapy by endoscopy,which can be performed by either endoscopic resection or endoscopic ablation.Endoscopic resection consists of either endoscopic mucosal resection(preferred in cases of adenocarcinoma)or endoscopic submucosal dissection(preferred in cases of squamous cell carcinoma).Endoscopic ablation can be performed by either radiofrequency ablation,cryotherapy,argon plasma coagulation or photodynamic therapy,amongst others.Endoscopy can also assist in the management of complications post-esophageal surgery,such as anastomotic leaks and perforations.Finally,there is a growing role for endoscopy to manage end-of-life palliative symptoms,especially dysphagia.The growing use of esophageal stents,debulking therapy and dilation can assist in improving a patient’s quality of life.In this review,we examine the multiple roles of endoscopy in the management of patients with EC. | Osman Ahmed Jaffer A Ajani Jeffrey H Lee | 2019 | World Journal of Gastrointestinal Oncology2019，11，10： | 6 |
| 6 | Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up显示文摘AIM: To determine the prevalence of bipolar disorder(BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder(ADHD) through 14 years' follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type Ⅰ?and Ⅱ diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD(MTA). We used the diagnostic interview schedule for children(DISC), administered to both parents(DISC-P) and youth(DISCY). We compared the MTA study subjects with ADHD(n = 579) to a local normative comparison group(LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts(TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic(PM) and non-specific manic(NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD(1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time(df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability(BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG(χ2 = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM(df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2(A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies. | Ahmed Z Elmaadawi Peter S Jensen L Eugene Arnold Brooke SG Molina Lily Hechtman Howard B Abikoff Stephen P Hinshaw Jeffrey H Newcorn Laurence Lee Greenhill James M Swanson Cathryn A Galanter | 2015 | World Journal of Psychiatry2015，5，4： | 3 |
| 7 | Prognostic impact of the Bismuth-Corlette classification:Higher rates of local unresectability in stageⅢb hilar cholangiocarcinoma显示文摘Background:The Bismuth-Corlette(BC)classification is used to categorize hilar cholangiocarcinoma by proximal extension along the biliary tree.As the right hepatic artery crosses just behind the left bile duct,we hypothesized that BCⅢb tumors would have a higher likelihood of local unresectability due to involvement of the contralateral artery.Methods:A retrospective review of a prospectively maintained database identified patients with hilar cholangiocarcinoma taken to the operating room for intended curative resection between April 2008 and September 2016.Cases were assigned BC stages based on preoperative imaging.Results:Sixty-eight patients were included in the study.All underwent staging laparoscopy after which 16 cases were aborted for metastatic disease.Of the remaining 52 cases,14 cases were explored and aborted for locally advanced disease.Thirty-eight underwent attempt at curative resection.After exclud-ing cases aborted for metastatic disease,the chance of proceeding with resection was 55.6%for BCⅢb staged lesions compared to 80.0%of BCⅢa lesions and to 82.4%for BCⅠ-Ⅲa staged lesions(P<0.05).About 44.4%of BCⅢb lesions were aborted for locally advanced disease versus 17.6%of remaining BC stages.Conclusions:When hilar cholangiocarcinoma is preoperatively staged as BCⅢb,surgeons should antici-pate higher rates of locally unresectable disease,likely involving the right hepatic artery. | Michael J Passeri Maria R Baimas-George Jesse K Sulzer David A Iannitti John B Martinie Erin H Baker Lee M Ocuin Dionisios Vrochides | 2020 | Hepatobiliary & Pancreatic Diseases International2020，19，2： | 3 |
| 8 | Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma显示文摘BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in HCC.AIM To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to RO7070179.METHODS In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of RO7070179.RESULTS Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased toxicity.This study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes in either m RNA level or DCE-MRI within 1 cycle of therapy. | Jennifer Wu Merly Contratto Krishna P Shanbhogue Gulam A Manji Bert H O'Neil Anne Noonan Robert Tudor Ray Lee | 2019 | World Journal of Clinical Oncology2019，10，3： | 2 |
| 9 | DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice显示文摘 | Meira Lisiane B Bugni James M Green Stephanie L Lee Chung-Wei Pang Bo Borenshtein Diana Rickman Barry H Rogers Arlin B Moroski-Erkul Catherine A McFaline Jose L Schauer David B Dedon Peter C Fox James G Samson Leona D | 2008 | Journal of Clinical Investigation2008，，7： | 2 |
| 10 | 卒中介入治疗培训指南:国际多学会共识文件显示文摘1背景
缺血性卒中是全球人口死亡和残疾的首要原因。很多急性大血管闭塞(emergent large vesselocclusion,ELVO)患者都会遗留长期残疾。事实上,这些颅内大动脉闭塞经常会导致大面积脑损伤,进而造成患者死亡或严重致残。 | Lavine SD Cockroft K Hoh B Bambakidis N Khalessi AA Woo H Riina H Siddiqui A Hirsch JA Chong W Rice H Wenderoth J Mitchell P Coulthard A Signh TJ Phatorous C Khangure M Klurfan P ter Brugge K Iancu D Gunnarsson T Pongpech S Rodesch G Soderman M Taylor A Krings T Orbach D Picard L Suh DC Zheng HQ Jansen O Muto M Szikora I Pierot L Brouwer P Gralla J Renowden S Andersson T Fiehler J Turjman F White P Januel AC Spelle L Kulcsar Z Chapot R Biondi A Dima S Taschner C Szajner M Krajina A Sakai N Matsumaru Y Yoshknura S Ezura M Fujinaka T Iihara K Ishii A Higashi T Hirohata M Hyodo A Ito Y Kawanishi M Kiyosue H Kobayashi E Kobayashi S Kuwayama N Matsumoto Y Miyachi S Murayama Y Nagata I Nakahara I Nemoto S Niimi Y Oishi H Satomi J Satow T Sugiu K Tanaka M Terada T Yamagami H Diaz O Lylyk P Jayaraman MV Patsalides A Gandhi CD Lee SK Abruzzo T Albani B Ansari SA Arthur AS Baxter BW Bulsara KR Chen M Almandoz JE Fraser JF Heck DV Hetts SW Hussain MS Klucznik RP Leslie-Mawzi TM Mack WJ McTaggart RA Meyers PM Mocco J Prestigiacomo CA Pride GL Rasmussen PA Starke RM Sunenshine PJ Tarr RW Frei DF Pabo M Nogueira RG Zaidat OO Jovin T Linfante I Yavagal D Liebeskind D Novakovic R Pongpech S 许岩 孙瑞 郭芮兵 | 2017 | 国际脑血管病杂志2017，25，5： | 2 |
| 11 | Full-thickness intraperitoneal excision by transanal endoscopic microsurgery does not increase short-term complications显示文摘 | Justine A Gavagan Mark H Whiteford Lee L Swanstrom | 2004 | The American Journal of Surgery2004，，5： | 2 |
| 12 | Identification of three genetic loci controlling leaf senescence in Arabidopsis thaliana显示文摘 | OH S A PARK J H LEE G I PACK K H PARK S K NAM H G | 1997 | Plant Journal1997，12，3： | 1 |
| 13 | Adsorption and diffusion of aromatics in AIPO4-5显示文摘 | CHIANG A S T LEE C K CHANG Z H | 1991 | Zeolites1991，11，4： | 1 |
| 14 | Adaptive Hopfield neural network for economic load dispatch显示文摘 | Lee K W Y Yome A S Park J H | 1998 | IEEE Transactions on Power System1998，13，2： | 1 |
| 15 | GPS travelling wave fault locator systems:investigation into the anomalous measurements related to lightning strikes显示文摘 | LEE H MOUSA A M | 1996 | IEEE Trans on Power Delivery1996，1，3： | 1 |
| 16 | Transformation of alfalfa with a bacterial fusion gene,Mannheimia haemolytica A1 leukotoxin50-gfp:response with Agrobacterium tumefaciens strains LBA4404 and C58显示文摘 | Lee R W H Ro R Shewen P Strommer J | 2004 | Plant Cell Tissue and Organ Culture2004，79，： | 1 |
| 17 | Design issues in CMOS differential LC oscillators 显示文摘 | HAJIMIRI A LEE T H | 1999 | IEEE J Solid-State Circuits1999，34，5： | 1 |
| 18 | Mesh Saliency显示文摘 | LEE C H VARSHNEY A JACOBS D W | 2005 | ACM Transaction on Graph2005，24，3： | 1 |
| 19 | P16 Gene therapy:a potentially efficacious modality for nasopharyngeal carcinoma显示文摘 | Lee A W Li J H Shi W | 2003 | Mol Cancer Ther2003，2，： | 1 |
| 20 | Catalytic growth of macroscopic carbon nanofiber bodies with high bulk density and high mechanical strength显示文摘 | Lee M K van der Dillen A J van Geus J W Jong K P de Bitter J H | 2006 | Carbon2006，44，： | 1 |
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