• 【≥ 80  岁COVID-19患者的临床特征及预后因素。】 复制标题 收藏 收藏
    DOI:10.1111/ggi.13960 复制DOI
    作者列表:Covino M,De Matteis G,Santoro M,Sabia L,Simeoni B,Candelli M,Ojetti V,Franceschi F
    BACKGROUND & AIMS: AIM:The aim of the present study was to describe the clinical presentation of patients aged ≥80 years with coronavirus disease 2019 (COVID-19), and provide insights regarding the prognostic factors and the risk stratification in this population. METHODS:This was a single-center, retrospective, observational study, carried out in a referral center for COVID-19 in central Italy. We reviewed the clinical records of patients consecutively admitted for confirmed COVID-19 over a 1-month period (1-31 March 2020). We excluded asymptomatic discharged patients. We identified risk factors for death, by a uni- and multivariate Cox regression analysis. To improve model fitting and hazard estimation, continuous parameters where dichotomized by using Youden's index. RESULTS:Overall, 69 patients, aged 80-98 years, met the inclusion criteria and were included in the study cohort. The median age was 84 years (82-89 years is interquartile range); 37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a severe and 25 (36.2%) a critical COVID-19 disease. A total of 23 (33.3%) patients had died at 30 days' follow up. Multivariate Cox regression analysis showed that severe dementia, pO2 ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for death. CONCLUSIONS:The present data suggest that risk of death could be not age dependent in patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this population. Severe COVID-19, as expressed by elevated lactate dehydrogenase and low oxygen saturation at emergency department admission, is associated with a rapid progression to death in these patients. Geriatr Gerontol Int 2020; ••: ••-••.
    背景与目标:
  • 【移植诱导的缺血再灌注损伤通过IL-1R8调节调节供体肾CD11c + F4/80 + 巨噬细胞的抗原呈递。】 复制标题 收藏 收藏
    DOI:10.1681/ASN.2019080778 复制DOI
    作者列表:Aiello S,Podestà MA,Rodriguez-Ordonez PY,Pezzuto F,Azzollini N,Solini S,Carrara C,Todeschini M,Casiraghi F,Noris M,Remuzzi G,Benigni A
    BACKGROUND & AIMS: BACKGROUND:In donor kidneys subjected to ischemia-reperfusion injury during kidney transplant, phagocytes coexpressing the F4/80 and CD11c molecules mediate proinflammatory responses and trigger adaptive immunity in transplantation through antigen presentation. After injury, however, resident renal macrophages coexpressing these surface markers acquire a proreparative phenotype, which is pivotal in controlling inflammation and fibrosis. No data are currently available regarding the effects of transplant-induced ischemia-reperfusion injury on the ability of donor-derived resident renal macrophages to act as professional antigen-presenting cells. METHODS:We evaluated the phenotype and function of intragraft CD11c+F4/80+ renal macrophages after cold ischemia. We also assessed the modifications of donor renal macrophages after reversible ischemia-reperfusion injury in a mouse model of congeneic renal transplantation. To investigate the role played by IL-1R8, we conducted in vitro and in vivo studies comparing cells and grafts from wild-type and IL-R8-deficient donors. RESULTS:Cold ischemia and reversible ischemia-reperfusion injury dampened antigen presentation by renal macrophages, skewed their polarization toward the M2 phenotype, and increased surface expression of IL-1R8, diminishing activation mediated by toll-like receptor 4. Ischemic IL-1R8-deficient donor renal macrophages acquired an M1 phenotype, effectively induced IFNγ and IL-17 responses, and failed to orchestrate tissue repair, resulting in severe graft fibrosis and aberrant humoral immune responses. CONCLUSIONS:IL-1R8 is a key regulator of donor renal macrophage functions after ischemia-reperfusion injury, crucial to guiding the phenotype and antigen-presenting role of these cells. It may therefore represent an intriguing pathway to explore with respect to modulating responses against autoantigens and alloantigens after kidney transplant.
    背景与目标:
  • 【活体肝脏供体的CT评估: 100-kVp加迭代重建方案能否为肝移植提供准确的肝脏体积和血管解剖结构,并减少辐射和造影剂剂量?】 复制标题 收藏 收藏
    DOI:10.1097/MD.0000000000006973 复制DOI
    作者列表:Yoshida M,Utsunomiya D,Kidoh M,Yuki H,Oda S,Shiraishi S,Yamamoto H,Inomata Y,Yamashita Y
    BACKGROUND & AIMS: :We evaluated whether donor computed tomography (CT) with a combined technique of lower tube voltage and iterative reconstruction (IR) can provide sufficient preoperative information for liver transplantation.We retrospectively reviewed CT of 113 liver donor candidates. Dynamic contrast-enhanced CT of the liver was performed on the following protocol: protocol A (n = 70), 120-kVp with filtered back projection (FBP); protocol B (n = 43), 100-kVp with IR. To equalize the background covariates, one-to-one propensity-matched analysis was used. We visually compared the score of the hepatic artery (A-score), portal vein (P-score), and hepatic vein (V-score) of the 2 protocols and quantitatively correlated the graft volume obtained by CT volumetry (graft-CTv) under the 2 protocols with the actual graft weight.In total, 39 protocol-A and protocol-B candidates showed comparable preoperative clinical characteristics with propensity matching. For protocols A and B, the A-score was 3.87 ± 0.73 and 4.51 ± 0.56 (P < .01), the P-score was 4.92 ± 0.27 and 5.0 ± 0.0 (P = .07), and the V-score was 4.23 ± 0.78 and 4.82 ± 0.39 (P < .01), respectively. Correlations between the actual graft weight and graft-CTv of protocols A and B were 0.97 and 0.96, respectively.Liver-donor CT imaging under 100-kVp plus IR protocol provides better visualization for vascular structures than that under 120-kVp plus FBP protocol with comparable accuracy for graft-CTv, while lowering radiation exposure by more than 40% and reducing contrast-medium dose by 20%.
    背景与目标: : 我们评估了供体计算机断层扫描 (CT) 与较低管电压和迭代重建 (IR) 相结合的技术是否能为肝移植提供足够的术前信息。我们回顾性回顾了113个供体候选者的CT。在以下方案下进行肝脏动态对比增强CT: 方案A (n   =   70),120-kVp与滤波反投影 (FBP); 方案B (n   =   43),100-kVp与IR。为了使背景协变量相等,使用了一对一的倾向匹配分析。我们目视比较了肝动脉 (A-score) 、门静脉 (P-score) 、和2种方案的肝静脉 (V-score),并将2种方案下CT体积 (移植物-CTv) 获得的移植物体积与实际移植物重量定量相关。总共有39种方案-A和方案-B候选方案显示出具有可比性的术前临床特征和倾向匹配。方案A和方案B的A-得分为3.87   ±   0.73和4.51   ±   0.56 (P  < .01),P-得分为4.92   ±   0.27和5.0   ±   0.0 (P   =  .07),V-评分分别为4.23   ±   0.78和4.82   ±   0.39 (p  < .01)。方案A和B的实际移植物重量与移植物CTv之间的相关性分别为0.97和0.96。100-kVp + IR方案下的肝供体CT成像比120-kVp + FBP方案下的血管结构提供了更好的可视化,对移植物CTv具有相当的准确性,同时将辐射暴露降低40% 以上,并将造影剂剂量降低20%。
  • 【在每周工作80小时的情况下,腹腔镜胆囊切除术期间胆管损伤率降低。】 复制标题 收藏 收藏
    DOI:10.1001/archsurg.143.9.847 复制DOI
    作者列表:Yaghoubian A,Saltmarsh G,Rosing DK,Lewis RJ,Stabile BE,de Virgilio C
    BACKGROUND & AIMS: BACKGROUND:Considerable concern has been raised about the effects of restricted duty hours on surgical training. However, to our knowledge, the effect of the 80-hour resident workweek on operative outcomes after laparoscopic cholecystectomy has not been well studied. OBJECTIVE:To compare the rates of bile duct injury and overall complications after laparoscopic cholecystectomy before and after the institution of the duty-hour restriction. DESIGN:Retrospective review of patient medical records to determine morbidity and mortality before (January 1, 2000, to June 30, 2003; period 1) and after (July 1, 2003, to June 30, 2006; period 2) implementation of duty hour limitations. SETTING:Major public teaching hospital. PATIENTS:A total of 2470 patients who had undergone laparoscopic cholecystectomy. MAIN OUTCOME MEASURES:Bile duct injury and overall complication rates as determined using multivariate analysis. RESULTS:Overall, 2470 laparoscopic cholecystectomy procedures were performed, including 1353 in period 1 and 1117 in period 2. In period 2, more patients had acute cholecystitis as the indication for surgery (49% vs 35% in period 1, P < .001), and a higher percentage of patients were male (22% vs 18%, P = .01). The incidence of bile duct injury and total complications decreased in period 2 from 1% to 0.4%(P = .04) and from 5% to 2% (P < .001), respectively. Mortality was unchanged. Multivariate analysis revealed that period 2 was protective for bile duct injury (odds ratio, 0.31; 95% confidence interval, 0.1-0.96; P = .04). For complications, both female sex (odds ratio, 0.62; 95% confidence interval, 0.38-0.9) and surgery during period 2 (odds ratio, 0.46; 95% confidence interval, 0.28-0.75) were protective, whereas older age (odds ratio, 1.03; 95% confidence interval, 1.02-1.05) was associated with complications. CONCLUSION:At a major public teaching hospital, the bile duct injury rate and the overall complication rate decreased after implementation of the 80-hour workweek.
    背景与目标:
  • 【血红蛋白F维多利亚禧年 (α2 A γ 2 80 Asp-Try)。】 复制标题 收藏 收藏
    DOI:10.1016/0005-2795(75)90230-5 复制DOI
    作者列表:Ahern E,Holder W,Ahern V,Serjeant GR,Serjeant BE,Forbes M,Brimhall B,Jones RT
    BACKGROUND & AIMS: :A new A gamma chain haemoglobin variant, haemoglobin F Victoria Jubilee, with an electrophoretic mobility slightly anodal to haemoglobin F Port Royal, was found in a Jamaican infant. The amino acid residue substitution of 80 Aspartic Acid leads to Tyrosine was associated with alanine in position 136. Haemoglobin F Victoria Jubilee constituted about 7.0 percent of the total haemoglobin F.
    背景与目标: : 在牙买加婴儿中发现了一种新的A γ 链血红蛋白变体,血红蛋白F维多利亚禧年,其电泳活动性与皇家港口的血红蛋白略有阳极。80天冬氨酸的氨基酸残基取代导致酪氨酸在136位与丙氨酸有关。血红蛋白F维多利亚禧年约占总血红蛋白F的7.0%。
  • 【下颌小梁骨作为80岁男女骨折的指标。】 复制标题 收藏 收藏
    DOI:10.1111/eos.12087 复制DOI
    作者列表:Hassani-Nejad A,Ahlqwist M,Hakeberg M,Jonasson G
    BACKGROUND & AIMS: :The objective of the present study was to compare assessments of the mandibular bone as fracture risk indicators for 277 men and women. The mandibular trabecular bone was evaluated in periapical radiographs, using a visual index, as dense, mixed dense and sparse, or sparse. Bone texture was analysed using a computer-based method in which the number of transitions from trabeculae to intertrabecular spaces was calculated. The sum of the sizes and intensities of the spaces between the trabeculae was calculated using Jaw-X software. Women had a statistically significantly greater number of fractures and a higher frequency of sparse mandibular bone. The OR for having suffered a fracture with visually sparse trabecular bone was highest for the male group (OR = 5.55) and lowest for the female group (OR = 3.35). For bone texture as an indicator of previous fracture, the OR was significant for the female group (OR = 2.61) but not for the male group, whereas the Jaw-X calculations did not differentiate between fractured and non-fractured groups. In conclusion, all bone-quality assessments showed that women had a higher incidence of sparse trabecular bone than did men. Only the methods of visual assessment and trabecular texture were significantly correlated with previous bone fractures.
    背景与目标: : 本研究的目的是比较下颌骨作为277男性和女性骨折风险指标的评估。在根尖周x线片中评估下颌小梁骨,使用视觉指数为致密,混合致密和稀疏或稀疏。使用基于计算机的方法分析了骨骼纹理,其中计算了从小梁到小梁间空间的过渡次数。使用Jaw-X软件计算小梁之间空间的大小和强度之和。女性的骨折数量在统计学上显着增加,下颌骨稀疏的频率更高。患有视觉稀疏骨小梁骨折的OR在男性组中最高 (OR = 5.55),在女性组中最低 (OR = 3.35)。对于骨质地作为先前骨折的指标,OR对女性组 (OR = 2.61) 很重要,但对男性组则不重要,而Jaw-X计算并未区分骨折组和非骨折组。总之,所有骨质量评估表明,女性的稀疏骨小梁发生率高于男性。只有视觉评估和小梁纹理的方法与先前的骨折显着相关。
  • 【80岁及以上患者的肺癌。】 复制标题 收藏 收藏
    DOI:10.1016/j.lungcan.2008.10.020 复制DOI
    作者列表:Satoh H,Kurishima K,Nakamura R,Ishikawa H,Kagohashi K,Ohara G,Ishikawa S,Ohtsuka M,Sekizawa K,Hizawa N
    BACKGROUND & AIMS: OBJECTIVES:The purpose of this study is to examine clinical and pathological features, treatment modality approaches in the elderly, especially in patients aged 80 years and older. METHODS:From the databases at two educational hospitals during the period from January 1978 and December 2007, medical records of lung cancer patients were retrospectively reviewed. The patient population was divided into three age groups: less than 70 years (the <70 age group), 70-79 years (the 70-79 age group), and 80 years or older (the > or =80 age group). Time trends were also studied in two-time intervals: first study period up to 1997, which represents past practice standards, the second study period up to 2007, which represents contemporary practice. RESULTS:Patients aged 80 years and older comprised 7.5% of 2775 consecutive patients with lung cancer, and there was a rapid increase in the proportion of patients aged 80 years or older from the earlier to the later time period. The > or =80 age group had higher proportion of poor performance status (PS) and comorbid disease than the <70 age group and the 70-79 age group. Unchanged proportion of patients with poor PS and advanced disease at presentation were observed in the > or =80 age group. The > or =80 age group was less likely to be subjected to surgery or chemotherapy, and had inferior outcomes when compared with the 70-79 age group and the <70 age group. Survival improvement was not observed in the > or =80 age group. Multivariate analysis showed good PS, early clinical stage and surgery were favorable prognostic factors in the > or =80 age group. CONCLUSION:In order to improve the outcome, detection of early stage lung cancer in patients with good PS and thorough pretreatment evaluation for appropriate treatment are indeed essential even for the > or =80 age group of patients.
    背景与目标:
  • 【来自Madin-Darby犬肾细胞的顶端分泌的80 kDa糖蛋白的翻译后修饰和结合特性: 与基底分泌的纤连蛋白的C末端部分相似。】 复制标题 收藏 收藏
    DOI:10.1016/0003-9861(91)90049-o 复制DOI
    作者列表:Han JR,Suiko M,Liu CC,Liu MC
    BACKGROUND & AIMS: :Apically secreted 80-kDa glycoprotein (gp 80) from Madin-Darby canine kidney cells was found to be immunoprecipitated by the polyclonal antiserum against fibronectin or a monoclonal antibody specific for the fibronectin C-terminal fibrin binding domain. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), gp 80 migrated as a doublet band under nonreducing conditions. Under reducing conditions, gp 80 was resolved into three distinct bands, respectively of 45-, 40-, and 35-kDa molecular mass. Analysis by two-dimensional SDS-PAGE revealed that gp 80 exists in two molecular forms: one consisting of a 45-kDa subunit and a 40-kDa subunit, and one consisting of a 45-kDa subunit and a 35-kDa subunit. V-8 protease mapping indicated the 40 and 35-kDa subunits as being of the same homologous group and also as bearing partial homology to the 45-kDa subunit. Radioactive labeling revealed that labeled gp 80 was subjected to covalent modifications by sulfation and phosphorylation. Sulfate analysis showed that [35S]sulfate-labeled gp 80 contained ca. 2.45 +/- 0.07% tyrosine-bound [35S]sulfate with the rest being presumably carbohydrate-bound. [32P]-Phosphate-labeled gp 80, on the other hand, was found to contain serine-O-phosphate as the predominant phosphorylated amino acid residue. Employing the affinity gel fractionation technique, it was shown that gp 80 exhibited binding affinities toward heparin and fibrin. Binding of gp 80 to heparin-agarose or fibrin-Sepharose, however, was inhibited in the presence of added fibronectin or the monoclonal antibody. Tryptic peptide mapping revealed common peptide spots between fibronectin and the three subunits of gp 80. Furthermore, Western blot analysis showed that fibronectin could be recognized and bound by anti-gp 80 antibodies. These results indicate that gp 80 bears both structural and functional similarities to the C-terminal portion of the fibronectin molecule.
    背景与目标: : 发现从Madin-Darby犬肾细胞中分泌的80 kDa糖蛋白 (gp 80) 被针对纤连蛋白的多克隆抗血清或对纤连蛋白C末端纤维蛋白结合域具有特异性的单克隆抗体免疫沉淀。在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳 (sds-page) 下,gp 80在非还原条件下以双峰带的形式迁移。在还原条件下,gp 80分解为三个不同的带,分别为45,40和35 kDa分子量。通过二维sds-page进行的分析表明,gp 80以两种分子形式存在: 一种由45 kDa亚基和40 kDa亚基组成,另一种由45 kDa亚基和35 kDa亚基组成。V-8蛋白酶作图表明40和35 kDa亚基属于同一同源组,并且与45 kDa亚基具有部分同源性。放射性标记显示,标记的gp 80通过硫酸化和磷酸化进行共价修饰。硫酸盐分析表明,[35S] 硫酸盐标记的gp 80含有约2.45 +/- 0.07% 酪氨酸结合的 [35S] 硫酸盐,其余的大概是碳水化合物结合的。[32P]-磷酸盐标记的gp 80,另一方面,发现含有丝氨酸-O-磷酸作为主要的磷酸化氨基酸残基。使用亲和凝胶分级技术,表明gp 80表现出与肝素和纤维蛋白的结合亲和力。gp 80与肝素-琼脂糖或纤维蛋白-琼脂糖的结合,在添加纤连蛋白或单克隆抗体的情况下被抑制。胰蛋白酶肽作图显示纤连蛋白与gp 80的三个亚基之间的共同肽点。此外,蛋白质印迹分析表明,纤连蛋白可以被抗gp 80抗体识别和结合。这些结果表明,gp 80与纤连蛋白分子的C端部分具有结构和功能相似性。
  • 【有证据支持在用250 kVp x射线或中子照射后,V79-4的放射敏感性突变体中存在有效的DNA双链断裂重联。】 复制标题 收藏 收藏
    DOI:10.1016/0921-8777(90)90056-b 复制DOI
    作者列表:Fox JC
    BACKGROUND & AIMS: :The repair of ionising-radiation-induced DNA double-strand break type damage was measured by Kohn neutral elution in an X-ray-sensitive mutant of V79-4, irs1. This was done in order to investigate further the likelihood that irs1 carries a defect which leads to error-prone repair of DNA damage, and not simply a reduced ability to rejoin DNA double-strand breaks. The mutant displayed an equal increase in sensitivity to the lethal effects of neutrons, as compared to X-rays. Both irs1 and V79-4 showed an increased sensitivity to the killing effects of neutrons of around 2 at 10% survival. irs1 also showed an exponential survival after either X-rays or neutrons. The induction of DNA double-strand breaks was measured in both cell lines over a dose range of 10-40 Gy using Kohn neutral filter elution. Induction of breaks by X-rays in irs1 seemed to increase slightly with dose, relative to induction in V79-4, so that at 40 Gy 1.5 times more DNA double-strand breaks were measured in irs1 cells than in V79-4. Neutron irradiation resulted in a more similar level of induction in either strain after 10-40 Gy. This difference in induction of damage may be due to a different cell-cycle composition in either cell line. The rejoining of X-ray induced double-strand breaks showed a very similar pattern (on a percentage rejoined basis) in both cell lines, although from the induction data at 40 Gy, the dose at which rejoining was measured, fewer breaks were rejoined in V79-4 but also fewer breaks remained unsealed. Neutron-induced breaks, however, were rejoined more efficiently in irs1 again on a percentage basis, but also in absolute terms since similar induction was seen after 40 Gy. This data, together with the differences seen in the rejoining of X-ray compared to neutron induced breaks, may indirectly support the proposal that irs1 is a misrepair mutant.
    背景与目标: : 电离辐射诱导的DNA双链断裂型损伤的修复是通过Kohn中性洗脱在V79-4的x射线敏感突变体irs1中进行的。这样做是为了进一步研究irs1携带缺陷的可能性,该缺陷导致容易出错的DNA损伤修复,而不仅仅是降低重新连接DNA双链断裂的能力。与x射线相比,该突变体对中子致死效应的敏感性相同。irs1和V79-4在10% 存活时对中子的杀伤作用均显示出增加的敏感性,约为2。irs1在x射线或中子后也显示出指数生存。使用Kohn中性滤镜洗脱在10-40 Gy的剂量范围内测量了两种细胞系中DNA双链断裂的诱导。相对于V79-4中的诱导,irs1中x射线对断裂的诱导似乎随剂量略有增加,因此在40 Gy时,irs1细胞中测得的DNA双链断裂比V79-4中多1.5倍。10-40 Gy后,中子辐照在任一菌株中的诱导水平均更为相似。损伤诱导的这种差异可能是由于两种细胞系中的细胞周期组成不同所致。X射线诱导的双链断裂的重新结合在两种细胞系中显示出非常相似的模式 (以百分比重新结合为基础),尽管从40 gy的诱导数据 (测量重新结合的剂量) 来看,在V79-4中重新结合的断裂更少,但仍保持未密封的断裂更少。然而,中子诱导的断裂在irs1中再次以百分比为基础更有效地重新结合,但也以绝对值重新结合,因为在40 Gy之后看到了类似的诱导。该数据以及与中子诱导的断裂相比,x射线重新结合所看到的差异,可能间接支持irs1是误修突变体的提议。
  • 【Αa66-80肽与可溶性 α-晶体蛋白相互作用并诱导其聚集和沉淀: 与年龄相关的白内障形成的贡献。】 复制标题 收藏 收藏
    DOI:10.1021/bi301662w 复制DOI
    作者列表:Kannan R,Santhoshkumar P,Mooney BP,Sharma KK
    BACKGROUND & AIMS: :Formation of protein aggregates in the aging eye lens has been shown to correlate with progressive accumulation of specific low-molecular weight (LMW) peptides derived from crystallins. Prominent among the LMW fragments is αA66-80, a peptide derived from αA-crystallin and present at higher concentrations in the water-insoluble nuclear fractions of the aging lens. The αA66-80 peptide has amyloid-like properties and preferentially insolubilizes α-crystallin from soluble lens fractions. However, the specific interactions and mechanisms by which the peptide induces α-crystallin aggregation have not been delineated. To gain insight into the mechanisms of peptide-induced aggregation, we investigated the interactions of the peptide with α-crystallin by various biochemical approaches. The peptide weakens α-crystallin chaperone ability and drastically promotes α-crystallin aggregation via the formation of insoluble peptide-protein complexes through transient intermediates. 4,4'-Dianilino-1,1'-binaphthyl-5,5'-disulfonic acid studies suggest that the peptide induces changes in the hydrophobicity of α-crystallin that could trigger the formation and growth of aggregates. The peptide-α-crystallin aggregates were found to be resistant to dissociation by high ionic strengths, whereas guanidinium hydrochloride and urea were effective dissociating agents. We conclude that the αA66-80 peptide forms a hydrophobically driven, stable complex with α-crystallin and reduces its solubility. Using isotope-labeled chemical cross-linking and mass spectrometry, we show that the peptide binds to multiple sites, including the chaperone site, the C-terminal extension, and subunit interaction sites in αB-crystallin, which may explain the antichaperone property of the peptide and the consequential age-related accumulation of aggregated proteins. Thus, the α-crystallin-derived peptide could play a role in the pathogenesis of cataract formation in the aging lens.
    背景与目标: : 已显示老化眼晶状体中蛋白质聚集体的形成与衍生自晶体蛋白的特定低分子量 (LMW) 肽的逐渐积累相关。LMW片段中最突出的是 αA66-80,这是一种衍生自 α a-晶体蛋白的肽,以较高浓度存在于老化晶状体的水不溶性核部分中。Αa66-80肽具有类似淀粉样蛋白的特性,并且优先使可溶性晶状体部分中的 α-晶体蛋白不溶解。然而,尚未描述肽诱导 α-晶体蛋白聚集的特定相互作用和机制。为了深入了解肽诱导聚集的机制,我们通过各种生化方法研究了肽与 α-晶体蛋白的相互作用。该肽通过瞬时中间体形成不溶性肽-蛋白质复合物,削弱 α-晶体蛋白伴侣的能力,并极大地促进 α-晶体蛋白聚集。4,4 '-Dianilino-1,1'-binaphthyl-5,5 '-二磺酸研究表明,该肽诱导 α-晶体蛋白疏水性的变化,这可能触发聚集体的形成和生长。发现肽-α-晶体蛋白聚集体可耐因高离子强度而解离,而盐酸胍和尿素是有效的解离剂。我们得出的结论是,αA66-80肽与 α-晶体蛋白形成疏水驱动的稳定复合物,并降低其溶解度。使用同位素标记的化学交联和质谱,我们显示该肽与多个位点结合,包括伴侣位点,C末端延伸和 α b-晶体蛋白中的亚基相互作用位点,这可以解释肽的抗伴侣特性以及随之而来的与年龄相关的聚集蛋白的积累。因此,α-晶状体蛋白衍生肽可能在衰老晶状体中白内障形成的发病机理中起作用。
  • 【回复: Yano Masashi Yano,Imamoto Takashi,Hiroyoshi Suzuki等。治疗前血清睾酮水平提高前列腺癌筛查效率的临床潜力。Eur urol 2007;51:375-80。】 复制标题 收藏 收藏
    DOI:10.1016/j.eururo.2007.03.045 复制DOI
    作者列表:Morgentaler A
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【年龄在80至94岁之间的年龄最大的田径运动员的成绩下降加速。】 复制标题 收藏 收藏
    DOI:10.1089/rej.2020.2337 复制DOI
    作者列表:Ganse B,Drey M,Hildebrand F,Knobe M,Degens H
    BACKGROUND & AIMS: :Physical performance declines with age, even in exercising, healthy individuals without major illnesses or orthopedic issues. The rate of performance decline is often reported to accelerate after the age of 70 years, but almost no data are available on performance in the fittest oldest-old. To assess their rate of decline in performance, the biggest data set of track and field athletes aged ≥80 years (1567 results) ever published was generated for different disciplines from German Athletics Federations including 1997-2019. Performance at age 80 years of athletes still participating at age 85 years was compared with those who discontinued. Only 1 of every 22 athletes competing at age 80 years still competed at age 90 years. The performance decline was more than three times as steep in athletes aged ≥80 years (on average 1.62%/year, men: 100 m, R = 0.31, p < 0.001; 200 m, R = 0.17, p = 0.037; long jump, R = -0.37, p < 0.001; shot put, R = -0.32, p < 0.001; discus, R = -0.34, p < 0.001; javelin, R = -0.43, p < 0.001; women: shot put, R = -0.24, p = 0.017; discus, R = -0.33, p = 0.010) compared with athletes aged 30-69 years (0.46%/year) and accelerated at an average of 67 years. This accelerated decline was most pronounced in the sprint disciplines and lowest in the throws. Performance at age 80 years was similar in athletes still participating at age 85 years to those who discontinued, and the variability in results was decreased after age 90 years. In conclusion, physical performance declines more than three times as fast after around the age of 67 years compared with before. This was particularly the case for sprinting but was not a result of dropout of poorer performing athletes.
    背景与目标: : 身体表现随着年龄的增长而下降,即使在运动中,健康的人没有重大疾病或骨科问题。据报道,性能下降的速度通常会在70岁以后加速,但是几乎没有关于适龄最老的性能的数据。为了评估他们的表现下降速度,德国田径联合会 (包括1997-2019) 针对不同学科生成了有史以来最大的年龄 ≥ 80岁的田径运动员数据集 (1567结果)。将仍在85岁时参加比赛的80岁运动员的表现与停赛者进行了比较。在80岁时参加比赛的22名运动员中,只有1名仍在90岁时参加比赛。年龄 ≥ 80岁的运动员成绩下降幅度超过3倍 (平均1.62%/年,男性: 100  m,r   =   0.31,p  <  0.001; 200  m,r   =   0.17,p   =   0.037; 跳远,r   =  -0.37,P  <  0.001; 铅球,r   =  -0.32,p  <  0.001; 铁饼,r   =  -0.34,p  <  0.001; 标枪,r   =  -0.43,p  <  0.001; 女子: 铅球,r   =  -0.24,P   =   0.017; discus,r   =  -0.33,p   =   0.010) 与30-69岁 (0.46%/年) 的运动员相比,平均加速67岁。这种加速下降在冲刺学科中最为明显,在投掷中最低。仍在85岁时参加比赛的运动员在80岁时的表现与停课运动员相似,并且在90岁时成绩的变异性降低了。总之,在67岁左右的年龄之后,身体机能下降的速度是以前的三倍以上。短跑尤其如此,但这并不是表现较差的运动员辍学的结果。
  • 【通过微观和纳米剂量计算评估用40 kVp,220 kVp和4 MV x射线照射的内皮细胞中放射性损伤。】 复制标题 收藏 收藏
    DOI:10.3390/ijms20246204 复制DOI
    作者列表:Tang N,Bueno M,Meylan S,Perrot Y,Tran HN,Freneau A,Dos Santos M,Vaurijoux A,Gruel G,Bernal MA,Bordage MC,Emfietzoglou D,Francis Z,Guatelli S,Ivanchenko V,Karamitros M,Kyriakou I,Shin WG,Incerti S,Villagrasa C
    BACKGROUND & AIMS: :The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV.
    背景与目标: : 这项工作的目的是通过使用机械方法研究不同x射线能量之间可能存在的早期生物学效应的差异。为此,进行了放射生物学实验,将细胞单层暴露于三个x射线能量,以评估早期DNA损伤的产量,特别是双链断裂 (dsb) 的产量。设置这些照射的模拟是为了了解获得的实验结果的差异。因此,分析了根据微剂量学光谱和早期DSB诱导的模拟结果,并将其与实验数据进行了比较。用40、220 kVp和4 MV x射线照射人脐静脉内皮细胞 (huvec)。使用Geant4蒙特卡洛模拟工具包及其扩展Geant4-DNA进行模拟。针对那些光子光谱,在代表细胞单层的10,000内皮细胞核上进行了旨在确定辐照细胞群吸收的能量变异性的微剂量计算。还使用计算链进行了纳米剂量模拟,该计算链允许在包括异染色质和常染色质的单个现实内皮细胞核模型上模拟物理,物理化学和化学阶段。根据每灰色 (Gy) 和每giga (109) 碱基对 (Gbp) 的快速DSB的产量对DNA损伤进行评分,并得出DSB的复杂性,以便与表示为每个细胞的组蛋白变体H2AX (γ-H2AX) 灶数的实验数据进行比较。当在40和220 kVp x射线之间进行比较时,所计算的在被照射的细胞群中的微剂量分布是相似的,而当与4 MV x射线相比时,所计算的微剂量分布是更高的。发现诱导的DSB/Gy/Gbp的模拟产量等于40和220 kVp的模拟产量,但大于4 MV的模拟产量,导致相对生物有效性 (RBE) 为1.3。此外,所考虑的光子光谱之间的DSB复杂度相似。模拟结果与IRSN (放射防护和放射生物研究所) 获得的实验数据非常吻合。尽管光子能量存在差异,但在微剂量和纳米剂量计算中比较40和220 kVp x射线时观察到的差异很少。然而,当比较40/220 kVp和4 mv x射线时观察到变化。由于模拟结果,这些变化可以通过能量低于10 keV的二次电子产生的差异来解释。
  • 【80  岁及以上骨质减少患者预防跌倒及抗骨质疏松的随机对照研究.】 复制标题 收藏 收藏
    DOI:10.1111/os.12701 复制DOI
    作者列表:Zhou J,Liu B,Qin MZ,Liu JP
    BACKGROUND & AIMS: :To evaluate the effects of two fall-prevention and anti-osteoporotic protocols in elderly patients with osteopenia (OPA). METHODS:The present randomized controlled study included patients with OPA (n =123). The age of these patients was ≥80 years old, with the mean age of 83.54 ± 2.99 years, and the male-to-female ratio was 2.97:1.00. Fall-prevention guidance was given to all patients. Patients in the experiment group (n = 62) orally received 600 mg/d of calcium carbonate, 0.5 μg/d of alfacalcidol, and 70 mg/week of alendronate, while patients in the control group (n = 61) orally received 600 mg/d of calcium carbonate and 0.5 μg/d of alfacalcidol for 18 months. The grip strength, gait speed, bone turnover markers, serum calcium, serum phosphorus, parathyroid hormone (PTH), and bone mineral density were measured, and the Timed Up and Go (TUG) test and the chair rising test (CRT) were performed. Falls, fragility fractures, medication compliance, and side effects of the drugs were recorded. RESULTS:The serum levels of bone turnover markers (type I procollagen amino-terminal peptide [P1NP], type I collagen carboxyl terminal peptide [β-CTx], and osteocalcin [OC]) decreased, while the bone mineral density of the lumbar spine and bilateral femoral neck increased after treatment in the experiment group (P < 0.05, P < 0.01). The rate of change in bone mineral density of the bilateral femoral neck was higher in the experiment group than the control group (3.43% vs 0.03%, P < 0.05; 2.86% vs -0.02%, P < 0.01). After treatment, the proportion of patients with increased hip T scores in the experiment group (66.1%, 41/62) was significantly higher than the proportion (35.0%, 21/60) in the control group (P = 0.001). The incidence of fall decreased in both groups after treatment compared to that before treatment (54.8% vs 33.9% and 54.1% vs 36.7%, respectively; P < 0.05). The incidence of fragility fractures was lower in the experiment group than the control group (8.1% vs 20.0%, P = 0.057). During the intervention period, the incidence of fragility fractures in patients who did not fall (3.8%, 3/79) was significantly lower than that in patients who fell (32.6%, 14/43) (P = 0.000). The risk of fragility fractures was significantly lower in patients who did not fall compared to patients who fell (relative risk: 0.117, 95% confidence interval: 0.035-0.384). CONCLUSION:The combination of alendronate sodium with alfacalcidol and calcium can significantly improve the bone mineral density of the lumbar spine and femoral neck. For older patients with OPA, subjectively paying attention to avoiding falls can significantly reduce the risk of fragility fractures.
    背景与目标:
  • 【对于年龄在80岁以下并接受根治性放射治疗的前列腺癌的男性,非前列腺癌的中位生存期超过10年。】 复制标题 收藏 收藏
    DOI:10.1186/1748-717X-2-17 复制DOI
    作者列表:Blood PA,Pickles T
    BACKGROUND & AIMS: :Treatment guidelines recommend that curative radiation treatment of prostate cancer be offered only to men whose life expectancy is greater than 10 years. The average life expectancy of North American males is less than 10 years after age 75, yet many men older than 75 years receive curative radiation treatment for prostate cancer. This study used the provincial cancer registry in British Columbia, Canada, to determine median non-prostate cancer survival for men who were aged 75 to 82 years at start of radiation treatment. Median survival was found to be greater than 10 years in men aged up to 80 years at the start of their radiation treatment. This finding suggests that radiation oncologists are able to appropriately select elderly men with greater than average life expectancy to receive curative radiation treatment.
    背景与目标: : 治疗指南建议仅对预期寿命超过10年的男性提供前列腺癌的根治性放射治疗。北美男性的平均预期寿命在75岁后不到10岁,但许多75岁以上的男性接受了前列腺癌的根治性放射治疗。这项研究使用了加拿大不列颠哥伦比亚省的省级癌症登记处,以确定放射治疗开始时年龄在75至82岁之间的男性的非前列腺癌中位生存期。在放射治疗开始时,年龄在80岁以下的男性的中位生存期已超过10年。这一发现表明,放射肿瘤学家能够适当选择寿命超过平均预期寿命的老年男性接受治愈性放射治疗。

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