An Environmental Scan of the National and Provincial Diagnostic Reference Levels in Canada for Common Adult Computed Tomography Scans

Several regulatory bodies have agreed that low-dose radiation used in medical imaging is a weak carcinogen that follows a linear, non-threshold model of cancer risk. While avoiding radiation is the best course of action to mitigate risk, computed tomography (CT) scans are often critical for diagnosis. In addition to the as low as reasonably achievable principle, a more concrete method of dose reduction for common CT imaging exams is the use of a diagnostic reference level (DRL). This paper examines Canada's national DRL values from the recent CT survey and compares it to published provincial DRLs as well as the DRLs in the United Kingdom and the United States of America for the 3 most common CT exams: head, chest, and abdomen/pelvis. Canada compares well on the international scale, but it should consider using more electronic dose monitoring solutions to create a culture of dose optimization.     

灯盏乙素介入IP3R-Ca2+途径抑制β淀粉样蛋白诱导的神经细胞凋亡

目的：观察灯盏乙素（Scu）对β淀粉样蛋白（Aβ）诱导的细胞模型中1，4，5-三磷酸肌醇受体（IP₃R）-Ca²⁺途径的影响，探讨其在阿尔茨海默病（AD）病程中可能发挥的积极作用。方法：选用神经母细胞瘤细胞分为对照组、Scu处理组、Aβ处理组、Aβ+Scu （高、中、低）处理组及Aβ+IP₃R拮抗剂组，用CCK-8法筛选药物浓度并检测各组细胞生存率；用酶联免疫吸附法检测各组细胞中1，4，5-三磷酸肌醇（IP₃）的含量；用蛋白印迹和实时荧光定量聚合酶链反应方法检测各组细胞IP₃R和凋亡相关因子Caspase-3、Bcl-2、Bax的蛋白及mRNA的表达水平；用激光共聚焦显微镜观察各组细胞内Ca²⁺浓度的变化；用AnnexinV/PI双染法测定各组细胞的凋亡率。结果：与对照组和Scu处理组相比，Aβ处理组细胞存活率下降，IP₃含量升高，IP₃R、Bax和Caspase-3的蛋白及mRNA表达上调，Bcl-2蛋白及mRNA的表达下调，细胞胞浆内Ca²⁺浓度及细胞凋亡率升高；Aβ+Scu处理组细胞中各检测指标的变化与Aβ处理组的结果正好相反，IP₃R通道下游指标的变化与Aβ+IP₃R拮抗剂组基本一致。结论：Scu能够下调通路蛋白IP₃、IP₃R的表达，抑制Aβ介导的Ca²⁺内流所致的细胞凋亡，可能通过对IP₃R-Ca²⁺途径的调控来影响AD病程。     

丹蛭降糖胶囊通过mTOR/S6K1信号通路对糖尿病肾病大鼠的干预作用研究

目的研究丹蛭降糖胶囊对糖尿病肾病大鼠的肾脏病理改变和足细胞自噬水平的影响,初步探讨其相应的作用机制。方法选取GK大鼠40只,采用醋酸脱氧皮质酮-盐皮下注射联合高脂饲料喂养诱导糖尿病肾病模型。造模成功后随机分为模型组、丹蛭降糖胶囊低剂量组[0.54 g/(kg·d)]、高剂量组[1.08 g/(kg·d)]、缬沙坦组[10 mg/(kg·d)],每组10只。另选取10只同周龄正常Wistar大鼠作为正常组。模型组和正常组给予等容积生理盐水。连续灌胃10周后检测空腹血糖(FBG)、血肌酐(SCr)、尿素氮(BUN)和尿微量蛋白(U-mAlb)。Western Blot检测肾小球p-mTOR、p-S6K1、Beclin-1、LC3和Nephrin蛋白的表达,HE染色和PAS染色后于光镜下观察肾脏病理变化,电镜下观察各组亚细胞形态结构变化。结果与正常组比较,模型组FBG、SCr、BUN、U-mAlb水平升高(P<0.01);与模型组比较,丹蛭降糖胶囊低、高剂量组和缬沙坦组U-mAlb水平降低(P<0.01)。模型组可见肾小球基底膜增厚,系膜基质沉积,足细胞损伤,各用药组均有不同程度改善,丹蛭降糖胶囊高剂量组足细胞内有较多自噬体形成。与正常组比较,模型组p-mTOR、p-S6K1的表达增高,Nephrin、Beclin-1和LC3的表达水平降低(P<0.01);与模型组比较,各用药组p-mTOR、p-S6K1的表达下降,Nephrin、Beclin-1和LC3的表达增高(P<0.01)。丹蛭降糖胶囊高剂量组和缬沙坦组Beclin1、LC3Ⅱ/LC3Ⅰ水平较丹蛭降糖胶囊低剂量组升高(P<0.05)。结论丹蛭降糖胶囊具有减轻糖尿病肾病大鼠U-mAIb、足细胞损伤及相关肾脏病理改变的作用,其机制可能与抑制mTOR/S6K1信号通路进而提高足细胞的自噬活性有关。     

Serum retinol-binding protein 4 is associated with insulin resistance in patients with early and untreated rheumatoid arthritis

ObjectiveRetinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA.MethodsIn this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40.ResultsIn those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36–52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05–1.11, P < 0.001) and 5% (1.05; 1.02–1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02).ConclusionElevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients     

Isolation and characterization of new human carrier peptides from two important vaccine immunogens

In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM₁₉₇ and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design.     

Mildly decreased preoperative bilirubin levels are associated with infections after shoulder and knee arthroplasty

Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls.     

地黄饮子加减方对血管性痴呆模型大鼠学习记忆能力及海马CA1区神经元损伤的影响

目的:观察地黄饮子加减方对血管性痴呆模型大鼠学习记忆能力及海马CA1区神经元的影响。方法:将84只SD雄性大鼠,按随机原则选出12只大鼠作为假手术组,其余72只大鼠采用两血管阻断法制备血管性痴呆模型,筛选60只模型大鼠,每组12只,随机分为模型组,尼莫地平组(0. 011 g·kg~(-1)),地黄饮子加减方高、中、低(4. 54,2. 27,1. 14 g·kg~(-1))剂量组。连续灌胃30 d后,Morris水迷宫检测大鼠学习记忆能力,苏木素-伊红(HE)观察海马CA1区神经元形态结构改变,透射电镜观察海马CA1区神经元超微结构变化,原位细胞凋亡检测法(TUNEL)检测海马CA1区细胞凋亡水平,免疫组化(IHC)检测海马CA1区组织磷脂酰肌醇3-激酶(PI3K),蛋白激酶B(Akt),半胱氨酸蛋白酶-3(Caspase-3)表达水平。结果:与假手术组比较,模型组大鼠逃避潜伏期显著延长,穿越原平台次数显著减少(P 0. 01),海马CA1区神经元形态均有不同程度地损伤,凋亡率显著增加(P 0. 01),PI3K,Akt的积分吸光度和平均积分吸光度明显降低(P 0. 01),Caspase-3的积分吸光度和平均积分吸光度显著增高(P 0. 01);与模型组比较,各给药组大鼠逃避潜伏期缩短(P 0. 05,P 0. 01),穿越原平台次数增加(P 0. 05,P 0. 01),PI3K,Akt的积分吸光度和平均积分吸光度值显著增高(P 0. 01),Caspase-3的积分光密度和平均积分吸光度不同程度降低(P 0. 05,P 0. 01)。结论:地黄饮子加减方可改善血管性痴呆模型大鼠学习记忆能力和海马CA1区神经元损伤,潜在机制可能与PI3K/Akt信号转导途径的激活,抑制大鼠海马CA1区神经细胞的凋亡有关。     

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.