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Fibromodulin reduces scar formation in adult cutaneouswounds by eliciting a fetal-like phenotype

Signal Transduction and Targeted Therapy 2017年第1期2卷 73-84页

作者： Zhong Zheng Aaron W James Chenshuang Li Wenlu Jiang Joyce Z Wang Grace X Chang Kevin S Lee Feng Chen Emily A Berthiaume Yao Chen Hsin Chuan Pan Eric C Chen Weiming Li Zhihe Zhao Xinli Zhang Kang Ting chia soo Division of Growth and Development School of DentistryUniversity of CaliforniaLos AngelesLos AngelesCA 90095USA UCLA Division of Plastic and Reconstructive Surgery Department of Orthopaedic SurgeryThe Orthopaedic Hospital Research CenterUniversity of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21287USA State Key Laboratory of Oral Diseases Department of OrthodonticsWest China School of StomatologySichuan UniversityChengduSichuan 610041China Department of Emergency Medicine Highland General HospitalOaklandCA 94602USA David Geffen School of Medicine University of CaliforniaLos AngelesLos AngelesCA 90095USA Central Laboratory School of StomatologyPeking UniversityBeijing 100081China Department of Orthopaedics the First Clinical Hospital of Harbin Medical UniversityHarbinHeilongjiang 150081China

Blocking transforming growth factor(TGF)β1 signal transduction has been a central strategy for scar reduction;however,this approach appears to be minimally ***,we show that fibromodulin(FMOD),a 59-kD small leucine-rich proteoglycan critical for normal collagen fibrillogenesis,significantly reduces scar formation while simultaneously increasing scar strength in both adult rodent models and porcine wounds,which simulate human cutaneous scar ***,FMOD uncouples promigration/contraction cellular signals from pro-fibrotic signaling by selectively enhancing SMAD3-mediated signal transduction,while reducing AP-1-mediated TGFβ1 auto-induction and fibrotic extracellular matrix ***,FMOD accelerates TGFβ1-responsive adult fibroblast migration,myofibroblast conversion,and ***,our findings strongly indicate that,by delicately orchestrating TGFβ1 activities rather than indiscriminately blocking TGFβ1,FMOD elicits fetal-like cellular and molecular phenotypes in adult dermal fibroblasts in vitro and adult cutaneous wounds in vivo,which is a unique response of living system undescribed *** together,this study illuminates the signal modulating activities of FMOD beyond its structural support functions,and highlights the potential for FMOD-based therapies to be used in cutaneous wound repair.

关键词： fetal scar cutaneous

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由慢病毒编码β-catenin shRNA产生的Wnt信号通路对鼠颅骨愈合的影响

由慢病毒编码β-catenin shRNA产生的Wnt信号通路对鼠颅骨愈合的...

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第十四次中国口腔颌面外科学术会议

作者：张蕾 Xu,Jiajia Meyers,Carolyn Yan,Noah Zou,Erin Ding,Catherine Ting,Kang soo,chia Pang,Shen James,Aaron Chang,Leslie 中国医科大学附属口腔医院口腔颌面外科 Johns Hopkins University Pathology University of California Los Angeles David Geffen School of Medicine UCLA Bioengineering UCLA Orthopaedic Surgery University of California Los AngelesOrthopaedic Hospital Reseach Center University of California San Diego School of Medicine

研究目的:从胚胎时期的骨骼类型,到胎儿骨的发育和骨修复,Wnt/β-catenin信号通路在成骨中都扮演了十分重要的作用[1]。体内拮抗Wnt信号通路的方法包括系统性拮抗或暂时性拮抗,包括基因途径[2],应用小分子抑制剂[3],或中和抗体[4]。我... 详细信息

研究目的:从胚胎时期的骨骼类型,到胎儿骨的发育和骨修复,Wnt/β-catenin信号通路在成骨中都扮演了十分重要的作用[1]。体内拮抗Wnt信号通路的方法包括系统性拮抗或暂时性拮抗,包括基因途径[2],应用小分子抑制剂[3],或中和抗体[4]。我们设计了一个能够在骨组织中局部应用并暂时可控的Wnt/β-catenin信号抑制剂。研究方法:首先在体内验证了β-catenin抑制能够影响颅骨愈合。然后将β-catenin shRNA编码的慢病毒或有GFP标记的随机序列sh RNA分别皮下注射到18周的NOD-SCID鼠的颅骨中线。在7天后,在NOD-SCID鼠的额骨或顶骨上分别做1.8mm的缺损。4周后,通过microCT,组织学分析,免疫组化等对结果进行分析。研究结果:慢病毒介导β-Catenin shRNA在体外抑制了73%鼠的骨髓间充质干细胞,在体内抑制了59%的骨愈合(图1)。在用慢病毒编码的β-catenin shRNA处理过的鼠中,从microCT重建中能看到额骨缺损愈合受到明显抑制(图2),定量骨愈合分析得到同样的结果(图3)。HE染色和组织学切片验证了同样的结果(图4)。免疫组化也验证了同样的结果(图5)。研究结论:慢病毒编码的β-Catenin shRNA对于抑制成骨有效,相比于顶骨,对于额骨的抑制作用更加明显。

关键词： Wnt信号通路骨愈合骨修复成骨颅骨 Beta-catenin shRNA 颅骨缺损膜内成骨

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Wnt1表达细胞系Nell-1缺失导致颅面部骨发育不足及出生后脑积水

Wnt1表达细胞系Nell-1缺失导致颅面部骨发育不足及出生后脑积水

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2020年中华口腔医学会口腔生物医学专业委员会第十次全...

作者：陈小燕王慧明俞孟流 Jong Kil Kim 齐慧川 Pin Ha Wenlu Jiang Eric Chen Xiangyou Luo Ryan Brent Needle Lloyd Baik Cathryn Yang 施洁珺 Jin Hee Kwak Kang Ting Xinli Zhang chia soo 浙江大学医学院附属口腔医院中日友好医院种植科 School of Dentistry University of California 吉林大学口腔医院正畸科四川大学华西口腔医院 UCLA Division of Plastic and Reconstructive Surgery and Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center University of California

目的:Nell-1蛋白表达增加与人类颅缝早闭(Craniosynostosis,CS)有关,此结果已在Nell-1过表达的转基因小鼠模型中得到验证。N-乙基-N-亚硝基脲(ENU)诱变的全身Nell-1敲除小鼠出生死亡率增加,并通常伴有骨骼异常,其中包括颅骨锁骨闭合发...

目的:Nell-1蛋白表达增加与人类颅缝早闭(Craniosynostosis,CS)有关,此结果已在Nell-1过表达的转基因小鼠模型中得到验证。N-乙基-N-亚硝基脲(ENU)诱变的全身Nell-1敲除小鼠出生死亡率增加,并通常伴有骨骼异常,其中包括颅骨锁骨闭合发育不良(CCD)样颅骨骨缺损。由于颅神经嵴细胞(CNCCs)在颅面组织发育过程中发挥着重要作用,本研究拟通过通过利用Nell-1在Wnt1表达细胞系中的特异性敲除转基因小鼠,进一步明确了Nell-1在颅面骨骼形成中的作用。

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The impact of urological resection and reconstruction on patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

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Asian Journal of Urology 2018年第3期5卷 194-198页

作者： Grace Hwei Ching Tan Nicholas B.Shannon Claramae Shulyn chia Lui Shiong Lee Khee Chee soo Melissa Ching Ching Teo Division of Surgical Oncology National Cancer Centre SingaporeSingapore Duke-NUS Medical School Singapore Department of Urology Singapore General HospitalSingapore

Objective:Cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)are increasingly being used to treat peritoneal *** resections and reconstruction(URR)are occasionally performed during the *** aim to evaluate the impact of these procedures on peri-operative outcomes of CRS and HIPEC ***:A retrospective review of a prospectively maintained database of all patients who underwent CRS-HIPEC from April 2001 to February 2016 was *** between patients who had surgery involving,and not involving URR were *** outcomes were the rate of major complications and the duration of stay in the intensive care unit(ICU)and *** outcomes were that of overall survival(OS)and prognostic factors that would indicate a need for ***:A total of 214 CRS-HIPEC were performed,21 of which involved a *** clinical characteristics did not vary between the groups(URR *** URR).Urological resections comprised of 52%bladder resections,24%ureteric resections,and 24%involving both bladder and ureteric *** bladder defects were closed primarily while ureteric reconstructions consisted of two end-to-end anastomoses,one ureto-uretostomy,five direct implantations into the bladder and three boari *** were more frequently required in patients with colorectal peritoneal disease(p Z 0.029),but was not associated with previous pelvic surgery(76%vs.54%,p Z 0.065).Patients with URR did not suffer more serious complications(14%vs.24%,p Z 0.42).ICU(2.2 days vs.1.4 days,p Z 0.51)and hospital stays(18 days vs.25 days,p Z 0.094)were not significantly *** a URR did not affect OS(p Z 0.99),but was associated with increased operation time(570 min vs.490 min,p Z 0.046).Conclusion:While concomitant URR were associated with an increase in operation time,there were no significant differences in postoperative complications or *** with colorectal peritoneal metastases a

关键词： Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Peritoneal carcinomatosis Urological procedures Urological reconstruction

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Gastric peritoneal carcinomatosis-a retrospective review

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World Journal of Gastrointestinal Oncology 2017年第3期9卷 121-128页

作者： Hwee Leong Tan Claramae Shulyn chia Grace Hwei Ching Tan Su Pin Choo David Wai-Meng Tai Clarinda Wei Ling Chua Matthew Chau Hsien Ng Khee Chee soo Melissa Ching Ching Teo Division of Surgical Oncology National Cancer Centre Singapore Dvision of Medical Oncology National Cancer Centre Singapore

AIM To characterize patients with gastric peritoneal carcinomatosis(PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of *** We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral *** We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority(n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175(64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. Thesepatients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114(66.7%), while cessation of chemotherapy occurred in 157(91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not(10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not(8.7 mo vs 14.6 mo, P < 0.001).CONCLUSION Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their

关键词： Peritoneal carcinomatosis Gastric cancer

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冠状动脉口部病变介入治疗中Szabo技术应用的安全性和可行性

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中华老年心脑血管病杂志 2011年第10期13卷 867-869页

作者：杨胜利刘惠亮 Aaron Wong Jack Tan 刘英张蛟 LIM soo Teik Paul chiam Stanley chia 武警总医院心内科北京100039 新加坡国家心脏中心心内科

目的分析冠状动脉口部病变PCI中造影和血管内超声(intra vascular ultrasonography,IVUS)结果 ,评价Szabo技术的成功率、安全性和可行性。方法回顾性分析Szabo技术治疗冠状动脉口部病变患者39例PCI结果。结果经桡动脉途径31例(79.5%),... 详细信息

目的分析冠状动脉口部病变PCI中造影和血管内超声(intra vascular ultrasonography,IVUS)结果 ,评价Szabo技术的成功率、安全性和可行性。方法回顾性分析Szabo技术治疗冠状动脉口部病变患者39例PCI结果。结果经桡动脉途径31例(79.5%),经股动脉途径8例(20.5%)。罪犯血管为左前降支26例(66.7%),右冠状动脉5例(12.8%),左回旋支及钝缘支3例(7.7%),后降支5例(12.8%)。支架置入后,对30例(76.9%)罪犯血管和9例(23.1%)边支血管进行了IVUS检查。手术成功36例(92.3%)。所有患者造影成功率为100%。IVUS检测罪犯血管准确支架置入到口部患者29例(96.7%)和支架近端轻度凸出患者1例(3.3%)。结论 Szabo技术用于冠状动脉口部病变PCI中是安全可行的,而且具有极高的造影成功率。经过IVUS检查证实大部分支架在冠状动脉口部病变处能准确置入。

关键词：冠状动脉疾病支架超声检查介入性冠状血管造影术

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Szabo技术在口部病变经皮冠状动脉介入治疗中应用的安全性和可行性(英文)

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心血管康复医学杂志 2011年第1期20卷 54-58页

作者：杨胜利刘惠亮 Aaron Wong Jack Tan 刘英张蛟 LIM soo Teik Paul chiam Stanley chia Koh Tian Hai Philip Wong 中国武警总医院心内科北京市100039 新加坡国家心脏中心心内科

背景和目的:冠状动脉口部病变的经皮冠状动脉介入(PCI)治疗手术操作难度大,易有并发症,既要支架准确植入口部病变,又要边支不受压。本研究探讨解决这一难题的Szabo技术的成功率、安全性和可行性。方法:Szabo技术是利用边支导丝(抛锚导丝... 详细信息

背景和目的:冠状动脉口部病变的经皮冠状动脉介入(PCI)治疗手术操作难度大,易有并发症,既要支架准确植入口部病变,又要边支不受压。本研究探讨解决这一难题的Szabo技术的成功率、安全性和可行性。方法:Szabo技术是利用边支导丝(抛锚导丝)穿过支架最靠近边支的支架网眼,防止支架前进时停止在口部病变外,保证主支导丝穿过支架腔。作者回顾性分析利用Szabo技术治疗39例病人冠状动脉口部病变的结果。手术操作成功定义:支架没有脱落,边支导丝没有退出。造影成功定义:支架准确植入到口部,而边支没有受压。血管内超声定义成功:支架准确植入到口部,近段没有突出,支架完全覆盖病变。39例病人中,男性28例,女性11例,年龄43～79,平均(65±12)岁。6F和7F指引导管分别用于35例(89.7%)和4(10.3%)例病人。经桡动脉途径31(79.5%)例和经股动脉途径8(20.5%)例。病变相关血管:前降支(LAD)26(66.7%)例,右冠(RCA)5(12.8%)例,旋支及钝缘支(LCX-OM)3(7.7%)例,后降支(PDA)5(12.8%)例。支架植入后30(76.9%)例病变相关血管和9(23.1%)例边支血管经过了血管内超声(IVUS)检查。结果:手术操作成功:36例(92.3%),这36例造影均成功(100%)。IVUS检测:支架准确植入口部者96.7%(29例/30例),支架近段轻度凸出的只有1例(3.3%)。没有发生严重并发症。结论:结果说明Szabo技术用于冠状动脉口部病变PCI成功率很高,是安全和可行的,值得推广。

关键词：血管成形术,经腔,经皮冠状动脉 Szabo技术冠状动脉疾病

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迂回隧道开挖对导坑隧道之影响探讨

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隧道建设 2007年第S2期27卷 150-154页

作者：陈志南贾儒龙赖正树柯志青台湾科技大学营建系平卡迪贸易有限公司

对于长大隧道而言,全断面隧道钻掘机(TBM)钻掘如施工顺利,可有效缩短工期,惟当遇及特殊地质状况时,亦可能导致TBM受困停工,此时采用迂回隧道绕至TBM机头前方解困是常用之解困方式之一,但迂回隧道挖掘对导坑隧道之影响机制不明,值得探讨... 详细信息

对于长大隧道而言,全断面隧道钻掘机(TBM)钻掘如施工顺利,可有效缩短工期,惟当遇及特殊地质状况时,亦可能导致TBM受困停工,此时采用迂回隧道绕至TBM机头前方解困是常用之解困方式之一,但迂回隧道挖掘对导坑隧道之影响机制不明,值得探讨。故本研究以雪山隧道导坑第十次TBM被埋受困之情况为仿真对象,将导坑视为本研究交叉区段之导坑隧道,利用三维程序FLAC3D探讨迂回隧道施作对导坑隧道之影响。导坑隧道为圆形断面(直径D=5m)、迂回隧道为方形断面(B×B=2m×2m)开挖。依本研究范围内所得之结论如下:由导坑隧道向外垂直破孔处左右两侧区域呈现应力增加趋势,其加压幅度可达初始应力10%~22%。45°破孔进入导坑隧道之锐角侧壁处在破孔后σ1、σ2、σ3分别增加47%、40%、-33.5%,与90°直交侧壁处之调整为20%、18%、6%要高出不少。另外钝角侧壁处其支撑承受之岩压在破孔后σ1、σ2、σ3分别增加21%、11%、-45%。

关键词： TBM 迂回隧道应力集中

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Prevalence,awareness and control of hypertension in Malaysia from 1980-2018:A systematic review and meta-analysis

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World Journal of Meta-Analysis 2020年第4期8卷 320-344页

作者： Man Jun soo Zhen Yee Chow Siew Mooi Ching Chun Han Tan Kai Wei Lee Navin Kumar Devaraj Hani Syahida Salim Vasudevan Ramachandran Poh Ying Lim Dhashani Sivaratnam Fan Kee Hoo Ai Theng Cheong Yook Chin chia Department of Family Medicine Universiti Putra MalaysiaSerdang 43400Malaysia Hospital Seberang Jaya Perai 13700Malaysia Malaysian Research Institute on Ageing Universiti Putra MalaysiaSerdang 43400Malaysia Department of Community Health Universiti Putra MalaysiaSerdang 43400Malaysia Department of Surgery Universiti Putra MalaysiaSerdang 43400Malaysia Department of Medicine Universiti Putra MalaysiaSerdang 43400Malaysia Department of Medical Sciences Sunway UniversityBandar Sunway 47500Malaysia

BACKGROUND Hypertension is a common public health problem worldwide and is a well-known risk factor for increased risk of cardiovascular diseases,contributing to high morbidity and ***,there has been no systematic review and meta-analysis of a multiethnic population such as that of *** To determine the trend in prevalence,awareness and control rate of hypertension in *** Systematic searches were conducted in six databases(PubMed,Scopus,Ovid,CINAHL,Malaysian Medical Repository and Malaysia Citation Index)for articles published between 1980 and *** authors reviewed the studies and performed quality assessment and data extraction *** estimates of hypertension prevalence,awareness and control rate were calculated using the DerSimonian-Laird random-effects *** and sensitivity analyses were *** We included 56 studies involving a total of 241796 *** overall pooled prevalence of hypertension aged≥18 years was 29.7%.The prevalence of hypertension was the lowest in the 1980s(16.2%,95%confidence interval(CI):13.4,19.0),increasing up to 36.8%(95%CI:6.1,67.5)in the 1990s,then decreasing to 28.7%(95%CI:21.7,35.8)in the 2000s and 26.8%(95%CI:21.3,32.3)in the *** prevalence of awareness was 51.4%(95%CI:46.6,56.3),while 33.3%(95%CI:28.4,38.2)of those on treatment had achieved control of their blood *** In Malaysia,three in ten adults aged≥18 years have hypertension,while four in ten adults aged≥30 years have *** out of ten people are aware of their hypertension status and only one-third of those under treatment achieved control of their *** efforts by policymakers and healthcare professionals to improve awareness and control of hypertension should be of high priority.

关键词： Prevalence Awareness Control Hypertension Blood pressure Malaysia Systematic review Meta-analysis

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