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1肌萎缩性侧索硬化蛋白激活小胶质细胞NLRP3炎性小体显示文摘小胶质细胞NLRP3炎性小体激活正在成为神经退行性变过程中神经炎症的关键因素。诸如β-淀粉样蛋白和α-突触核蛋白之类的致病性蛋白质聚集体触发小胶质NLRP3激活,从而导致半胱天冬酶-1激活和IL-1β的分泌。在小鼠肌萎缩性侧索硬化症(ALS)的SOD1G93A模型中,半胱天冬酶-1和IL-1β均促进疾病进展,提示小胶质NLRP3在该进程中发挥作用。然而先前的研究表明,SOD1G93A小鼠小胶质细胞不表达NLRP3,SOD1G93A蛋白在小胶质细胞中产生独立于NLRP3的IL-1β。本研究论证了使用Nlrp3-GFP基因敲入小鼠,在SOD1G93A小鼠中小胶质细胞表达NLRP3。本研究显示聚集和可溶性SOD1G93A均可激活小鼠原代小胶质细胞中的炎性小体,导致半胱天冬酶-1和IL-1β裂解,ASC斑点形成以及呈剂量和时间依赖性的IL-1β分泌。重要的是,SOD1G93A无法从缺乏Nlrp3的小胶质细胞或者用特异性NLRP3抑制剂MCC950预处理的小胶质细胞中诱导IL-1β分泌,从而证实NLRP3是介导SOD1诱导的小胶质细胞IL-1β分泌的关键炎症小体复合物。在TDP-43Q331K ALS小鼠模型中也观察到小胶质NLRP3上调,TDP-43野生型和突变蛋白亦可以NLRP3依赖性的方式激活小胶质炎性小体。从机制上讲,本研究确定了活性氧簇和ATP的生成是SOD1G93A介导的NLRP3激活所需的关键事件。总之,本研究的数据表明ALS小胶质细胞表达NLRP3,而病理ALS蛋白激活小胶质NLRP3炎性小体。因此,NLRP3抑制可能是阻止小胶质细胞神经炎症和ALS疾病进展的潜在治疗方法。Vandana Deora John D Lee Eduardo AAlbornoz Luke McAlary Cyril J Jagaraj Avril A B Robertson Julie D Atkin Matthew A Cooper Kate Schroder Justin J Yerbury Richard Gordon Trent MWoodruff 杜一星(编译) 2020神经损伤与功能重建2020,15,9:13
2Establishing proof of concept:Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus显示文摘Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative(microfracture) or replacement(autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration,with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma(PRP) and bone marrow aspirate concentrate(BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.Niall A Smyth Christopher D Murawski Amgad M Haleem Charles P Hannon Ian Savage-Elliott John G Kennedy 2012World Journal of Orthopedics2012,3,7:8
3The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating human sperm-egg recognition显示文摘在人的不孕病人的精子在场的最普通的损害之一是精子鸡蛋识别的自发的失败。尽管这个唯一的细胞的相互作用现在能被象 intracytoplasmic 精子注射(ICSI ) 那样的帮助繁殖策略乐意地绕过,最近的大规模流行病学的研究鼓励了这种技术的小心的使用并且为对为有缺点的精子鸡蛋识别负责的机制的进一步的研究加亮需要。这个领域里的以前的工作证实了为卵母细胞相互作用负责的精子领域在动态地在女繁殖的道在 epididymal 成熟和 capacitation 期间被修改以前在精子发生期间被形成。当为这些顺序的 maturational 事件的规定负责的因素无疑是复杂的时,新兴的研究识别了分子的女伴,加热吃惊蛋白质 A2 (HSPA2 ) ,,在人的精子的这些事件的一个关键管理者。HSPA2 是支持合拢,运输,和集会蛋白质建筑群的 70 kDa 热吃惊蛋白质家庭的一个充实睾丸的成员并且断然被相关与在 vitro 授精(IVF ) 成功。而且,从人的精子 proteome 减少了 HSPA2 的表示为跟随 IVF 和 ICSI 的积云矩阵疏开,精子鸡蛋识别和授精导致一个损害能力。在这评论,我们考虑在精子功能支持 HSPA2 的角色的证据并且探索它被在不肥沃的病人的精子弄空的潜在的机制。进管理精子的分子的机制的如此的信息提议小说卓见工作。Brett Nixon Elizabeth G Bromfield Matthew D Dun Kate A Redgrove Eileen A McLaughlin R John Aitken 2015Asian Journal of Andrology2015,17,4:8
4Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma显示文摘Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed.Erik W Larson Halloran E Peterson Wayne T Lamoreaux Alexander R MacKay Robert K Fairbanks Jason A Call Jonathan D Carlson Benjamin C Ling John J Demakas Barton S Cooke Christopher M Lee 2014World Journal of Clinical Oncology2014,5,2:5
5乙酰半胱氨酸在急性心肌梗塞溶栓治疗中的抗氧化作用显示文摘27例急性心肌梗塞患者用链激酶溶栓治疗,其中20例联合静脉滴注乙酰半胱氨酸(NAC)。结果显示:联合应用NAC治疗后血浆还原型谷胱甘肽(GSH)及GSH与氧化型谷胱甘肽(GSSG)之比(GSH/GSSG)显著性增高(P<0.05),伴随GSSG显著性降低(P<0.05)。NAC治疗组心指数亦明显高于对照组(P<0.01)。杨杰孚 IreneStafford Margaret A Arstall John D Horowitz 1996中华心血管病杂志1996,24,4:5
6Status review of mercury control options for coal-fired power plants显示文摘John H Pavlish Everett A Sondreal Michael D Mann Edwin S Olson Kevin C Galbreath Dennis L Laudal Steven A Benson 2003Fuel Processing Technology2003,,2:4
7Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer显示文摘Douglas K Rex John H Bond Sidney Winawer Theodore R Levin Randall W Burt David A Johnson Lynne M Kirk Scott Litlin David A Lieberman Jerome D Waye James Church John B Marshall Robert H Riddell 2002The American Journal of Gastroenterology2002,,6:3
8A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010显示文摘Stephen S Lim Theo Vos Abraham D Flaxman Goodarz Danaei Kenji Shibuya Heather Adair-Rohani Mohammad A AlMazroa Markus Amann H Ross Anderson Kathryn G Andrews Martin Aryee Charles Atkinson Loraine J Bacchus Adil N Bahalim Kalpana Balakrishnan John Balmes S 20122012 (9859)2012,,9859:3
9Malrotation: Current strategies navigating the radiologic diagnosis of a surgical emergency显示文摘The most accurate and practical imaging algorithm for the diagnosis of intestinal malrotation can be a complex and sometimes controversial topic.Since 1900,sig-nificant advances have been made in the radiographic assessment of infants and children suspected to have anomalies of intestinal rotation.We describe the cur-rent methods of abdominal imaging of malrotation along with their pros and cons.When associated with volvulus,malrotation is a true surgical emergency re-quiring rapid diagnosis and treatment.We emphasize the importance of close cooperation and communica-tion between radiology and surgery to perform an effective and efficient diagnostic evaluation allowing prompt surgical decision making.John J Tackett Eleanor D Muise Robert A Cowles 2014World Journal of Radiology2014,6,9:3
10The impact of patient age and aortic size on the results of aortobifemoral bypass grafting 1 1 Competition of interest: none. Published online Mar 6, 2003显示文摘Amy B Reed Michael S Conte Magruder C Donaldson John A Mannick Anthony D Whittemore Michael Belkin 2003Journal of Vascular Surgery2003,,:2
11Biomarkers for diet and cancer prevention research:potentials and challenges显示文摘当癌症发生被投射增加十年,对有效预防策略有需要。幸好,证据继续到改变饮食的习惯是为减少癌症风险并且为修改肿瘤的生物行为的一条有效、成本效率的途径的山。预兆,验证并且敏感简历标记,包括可靠地评估“吸入”或暴露到特定的食物或简历的那些活跃部件,估计被连接到癌症的至少一特定的生物“效果”,并且有效地作为滋养营养素的相互作用和遗传的功能预言单个“危险性”,对评估基本将从饮食的 interventions.These 简历标记有益于大多数的人,一定容易地温和,容易并且可靠地 assayed ,并且涉及 cancer.Theresponse 到食物的一个关键过程( es )预兆被简历的有效集中决定不仅到达目标织物的活跃食物部件,而且由目标 requiringmodification.Thus 的数量,对食物和他们的部件的这阀值回答将从对理解个性化的回答是更大的知识 ofnutrigenomics , proteomics 和 metabolomics 关键的单个 toindividual.The 变化。Cindy D DAVIS John A MILNER 2007Acta Pharmacologica Sinica2007,28,9:2
12Hepatitis B and C infection and liver disease trends among human immunodeficiency virus-infected individuals显示文摘AIM:To examine trends in and correlates of liver disease and viral hepatitis in an human immunodeficiency virus (HIV)-infected cohort. METHODS:The multi-site adult/adolescent spectrum of HIV-related diseases (ASD) followed 29 490 HIVinfected individuals receiving medical care in 11 U.S. metropolitan areas for an average of 2.4 years,and a total of 69 487 person-years,between 1998 and 2004. ASD collected data on the presentation,treatment,and outcomes of HIV,including liver disease,hepatitis screening,and hepatitis diagnoses. RESULTS:Incident liver disease,chronic hepatitis B virus (HBV),and hepatitis C virus (HCV) were diagnosed in 0.9,1.8,and 4.7 per 100 person-years. HBV and HCV screening increased from fewer than 20% to over 60% during this period of observation (P < 0.001). Deaths occurred in 57% of those diagnosed with liver disease relative to 15% overall (P < 0.001). Overall 10% of deaths occurred among individuals with a diagnosis of liver disease. Despite care guidelines promoting screening and vaccination for HBV and screening for HCV,screening and vaccination were not universally conducted or,if conducted,not documented. CONCLUSION:Due to high rates of incident liver disease,viral hepatitis screening,vaccination,and treatment among HIV-infected individuals should be a priority.Susan E Buskin Elizabeth A Barash John D Scott David M Aboulafia Robert W Wood 2011World Journal of Gastroenterology2011,17,14:2
13Advances in cellulose ester performance and application显示文摘Kevin J Edgar Charles M Buchanan John S Debenham Paul A Rundquist Brian D Seiler Michael C Shelton Debra Tindall 2001Progress in Polymer Science2001,,9:2
14Percutaneous transluminal angioplasty balloons for endoscopic ultrasound-guided pancreatic duct interventions显示文摘BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angioplasty balloon(PTAB),originally developed for vascular interventions,can be used to facilitate transmural(e.g.,transgastric)PD access and to dilate high-grade pancreatic strictures.AIM To describe the technique,efficacy,and safety of PTABs for EUS-guided PD interventions.METHODS Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database.PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire.The primary outcome was technical success.Secondary outcomes included incidence of adverse events(AEs)and need for early reintervention.RESULTS A total of 23 patients were identified(48%female,mean age 55.8 years).Chronic pancreatitis was the underlying etiology in 13(56.5%)patients,surgically altered anatomy(SAA)with stricture in 7(30.4%),and SAA with post-operative leak in 3(13.0%).Technical success was achieved in 20(87%)cases.Overall AE rate was 26%(n=6).All AEs were mild and included 1 pancreatic duct leak,2 cases of post-procedure pancreatitis,and 3 admissions for post-procedural pain.No patients required early re-intervention.CONCLUSION EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails.Jad P AbiMansour Barham K Abu Dayyeh Michael J Levy Andrew C Storm John A Martin Bret T Petersen Ryan J Law Mark D Topazian Vinay Chandrasekhara 2022World Journal of Gastrointestinal Endoscopy2022,14,8:2
15Trabecular Bone Score: A Noninvasive Analytical Method Based Upon the DXA Image显示文摘Barbara C Silva William D Leslie Heinrich Resch Olivier Lamy Olga Lesnyak Neil Binkley Eugene V McCloskey John A Kanis John P Bilezikian 2014J Bone Miner Res2014,,3:2
16End-stage renal disease is associated with increased post endoscopic retrograde cholangiopancreatography adverse events in hospitalized patients显示文摘AIM To determine if end-stage renal disease (ESRD) is a risk factor for post endoscopic retrograde cholangio-pancreatography (ERCP) adverse events (AEs). METHODS We performed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) 2011-2013. We identified adult patients who underwent ERCP using the International Classification of Diseases 9^(th) Revision (ICD-9-CM). Included patients were divided into three groups: ESRD, chronic kidney disease (CKD), and control. The primary outcome was post-ERCP AEs including pancreatitis, bleeding, and perforation determined based on specific ICD-9-CM codes. Secondary outcomes were length of hospital stay, in-hospital mortality, and admission cost. AEs and mortality were compared using multivariate logistic regression analysis.RESULTS There were 492175 discharges that underwent ERCP during the 3 years. The ESRD and CKD groups contained 7347 and 39403 hospitalizations respectively, whereas the control group had 445424 hospitalizations. Post-ERCP pancreatitis (PEP) was significantly higher in the ESRD group (8.3%) compared to the control group (4.6%) with adjusted odd ratio (aOR) = 1.7 (95% CI: 1.4-2.1, ~aP < 0.001). ESRD was associated with significantly higher ERCP-related bleeding (5.1%) compared to the control group 1.5% (aOR = 1.86, 95%CI: 1.4-2.4, ~aP < 0.001). ESRD had increased hospital mortality 7.1% vs 1.15% in the control OR = 6.6 (95%CI: 5.3-8.2, ~aP < 0.001), longer hospital stay with adjusted mean difference (aMD) = 5.9 d (95% CI: 5.0-6.7 d, ~aP < 0.001) and higher hospitalization charges aMD = $+82064 (95%CI: $68221-$95906, ~aP < 0.001). CONCLUSION ESRD is a risk factor for post-ERCP AEs and is associated with higher hospital mortality. Careful selection and close monitoring is warranted to improve outcomes.Tarek Sawas Fateh Bazerbachi Samir Haffar Won K Cho Michael J Levy John A Martin Bret T Petersen Mark D Topazian Vinay Chandrasekhara Barham K Abu Dayyeh 2018World Journal of Gastroenterology2018,24,41:2
17Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry显示文摘AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.Scott V Adams Dennis J Ahnen John A Baron Peter T Campbell Steven Gallinger William M Grady Loic LeMarchand Noralane M Lindor John D Potter Polly A Newcomb 2013World Journal of Gastroenterology2013,19,21:2
18A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010显示文摘Stephen S Lim Theo Vos Abraham D Flaxman Goodarz Danaei Kenji Shibuya Heather Adair-Rohani Mohammad A AlMazroa Markus Amann H Ross Anderson Kathryn G Andrews Martin Aryee Charles Atkinson Loraine J Bacchus Adil N Bahalim Kalpana Balakrishnan John Balmes S 2012The Lancet2012,,9859:2
19Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias显示文摘Steven L Higgins John D Hummel Imran K Niazi Michael C Giudici Seth J Worley Leslie A Saxon John P Boehmer Michael B Higginbotham Teresa De Marco Elyse Foster Patrick G Yong 2003Journal of the American College of Cardiology2003,,8:2
20Contractual Relations,Control,and Quality in the Hog Sector显示文摘 John D Lawrence 1999Review of Agricultural Economics1999,2,1:1
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