乙二胺为核心的PAMAM树枝状聚合物(5.0代)纳米材料溶液的遗传毒性研究

目的:研究乙二胺为核心的PAMAM树枝状聚合物(5.0代)纳米材料溶液的遗传毒性。方法:采用Ames试验平板掺入法,设3 985、797、139.4、31.88和6.376 μg/皿的5个乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液浓度组,在加与不加S9混合液的条件下观察回变菌落数。同时采用L5178Y细胞胞质分裂阻滞微核细胞组学试验,给予受试细胞终浓度分别为0.625、1.25、2.5、5、10 μg/mL的受试物,观察其微核组效应、剂量-效应和时间-效应关系。结果:受试物溶液各剂量组均未引起测试菌株回变菌落数明显增加,Ames试验结果为阴性。胞质分裂阻滞微核细胞组学试验中,与阴性对照组比较,1.25 μg/mL的受试物即可诱导受试细胞出现核芽(P<0.01);2.5 μg/mL及以上剂量可进一步诱使细胞出现总微核、Ⅰ型微核、Ⅱ型微核和核质桥效应(P<0.01),且存在明显的剂量-效应关系(除核质桥外,r值均>0.5,P均<0.05)。与阴性对照组比较,在5 μg/mL剂量下,乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液在9 h时即可诱导受试细胞的总微核、Ⅰ型微核、Ⅱ型微核和核芽增加(P<0.01);在18 h时出现核质桥数增加(P<0.01),各项指标在27 h达到峰值。结论:乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液对鼠伤寒沙门氏菌无致基因突变作用;对L5178Y细胞可诱导4类微核组效应,并有明显的剂量-效应和时间-效应关系;从剂量和时间来看,以核芽效应最为敏感。     

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited.Design, setting, participants, & measurement: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180.Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were ≤300 pg/ml (weeks 16 through 180) and median Ca×P values were ≤55 mg²/dl² (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events.Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk.Secondary hyperparathyroidism (SHPT) occurs often in chronic kidney disease (CKD). It is characterized by increases in the synthesis and secretion of parathyroid hormone (PTH) and by disturbances in calcium (Ca), phosphorus (P), and vitamin D metabolism (1). SHPT is a progressive disorder among those undergoing dialysis in whom PTH levels increase by an average of 6% per year (2). Elevated PTH, Ca, P, and Ca×P levels and alterations in vitamin D metabolism are associated with important adverse outcomes, including cardiovascular disease, in such patients (3–6).The long-term efficacy and safety of traditional therapies for SHPT have not been critically examined. Despite many years of clinical use, results from prospective clinical trials describing therapeutic responses to any vitamin D sterol among dialysis patients with SHPT lasting more than 13 mo are available from only six patients after 2 yr of follow-up (20). Sustained treatment with vitamin D alone often proves inadequate for dialysis patients with SHPT (7–9). Disturbances in calcium and phosphorus metabolism frequently disrupt therapy (10), rendering consistent biochemical control of the disorder difficult (8).Treatment with cinacalcet hydrochloride (cinacalcet) often concurrently lowers PTH, Ca, P, and Ca×P levels among dialysis patients with SHPT (11–14). Its use can provide sustained control of key biochemical parameters in those receiving traditional treatments for SHPT as judged by the achievement of values within the target ranges recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI^TM) (15). Unfortunately, a relatively small number of patients (n = 59) have been evaluated thus far, and efficacy results are available in only 16 subjects after 3 yr of follow-up (15). Confirmation of these preliminary findings is required.To further assess the long-term therapeutic efficacy of cinacalcet for managing SHPT among patients receiving dialysis, we measured the adequacy of control of biochemical outcomes for SHPT as judged by the achievement of recommended values (16) after 180 wk of cinacalcet therapy.     

Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway

Introduction  

The pineal gland hormone, melatonin, has been shown by numerous studies to inhibit the proliferation of estrogen receptor α (ERα)-positive breast cancer cell lines. Here, we investigated the role of melatonin in the regulation of breast cancer cell invasion.     

肠道微生态与酒精性肝病

<正>酒精性肝病(ALD)的发病机制目前仍不清楚,酒精的脂溶性及毒性可直接破坏肠黏膜屏障,导致宿主肠道通透性增加,失调的肠源性微生物群及其代谢产物通过被破坏的细胞间连接直接进入门脉系统,可能是发生ALD的基础和重要原因~([1,2])。肝病程度越重(如肝硬化)患者比健康人血液有更高水平的细菌数量及其代谢产物,高水平的细菌移位引起的感染极大地增加了酒精性肝硬化(alcoholic     

自制金属圆棒与双极电凝治疗鼻中隔偏曲矫正术中腭大动脉出血的疗效比较

目的 探讨自制金属圆棒与双极电凝在鼻中隔矫正术中腭大动脉出血止血的疗效。 方法 选取2013年5月至2016年8月住院行鼻中隔矫正手术的患者60例,符合入选标准的患者按照入院顺序,采用随机数字表法分为两组,A组(30例)采用圆棒砸平上颌骨棘突腭大动脉处,B组(30例)采用双极电凝止血上颌骨棘突腭大动脉处。比较两组腭大动脉出血量、止血时间及两组因腭大动脉出血形成血肿的例数。 结果 A组患者止血时间为(1.93±0.94)min;B组止血时间为(5.96±1.62)min。A组出血量为(25.5±10.5)mL, B组为(72.0±17.6)mL。 A组未出现血肿,B组血肿3例。 结论 自制金属圆棒砸平鼻中隔上颌骨鼻棘腭大动脉处止血时间较双极电凝组少,出血量少,术后腭大动脉继发性出血少,经济性高,值得在临床上推广应用。     

Volumetric cone-beam computed tomography evaluation and risk factor analysis of external apical root resorption with clear aligner therapy

ObjectivesTo investigate the prevalence and severity of external apical root resorption (EARR) volumetrically with clear aligner therapy using cone-beam computed tomography (CBCT) as well as determine the possible risk factors and develop a prediction model for EARR.Materials and MethodsIn this retrospective study, 320 incisors from 40 Class II patients treated with aligners (Invisalign) were included in this study. CBCT images were obtained at pretreatment (T0) and posttreatment (T1). Root volume was calculated by three-dimensional reconstruction of CBCT images, and apical tooth movement was measured from superimposed CBCT images. Changes in root volume were compared using paired t-tests, and the relationship between root volume loss and potential risk factors was analyzed by multiple linear regression.ResultsAll of the measured incisors showed root volume loss, with an average of 11.48 ± 6.70 mm³, and the prevalence of severe resorption was 0.625%. The prediction model for EARR included variables of posttreatment sagittal root position (SRP), extraction, tooth type, and apical intrusion and extrusion displacements, with an R² of 0.51. Age, sex, duration, pretreatment SRP, attachment, advancement, and retraction movements were excluded from the model.ConclusionsMost incisors showed mild to moderate resorption during aligner treatment; only a minimal percentage showed severe resorption. Posttreatment SRP (which showed the highest association with EARR), extraction, tooth type, and apical intrusion and extrusion displacements were risk factors for EARR.     

群体反应性抗体与器官移植

群体反应性抗体(PRA)是移植中最重要的免疫因素。研究证明移植排斥是由体液免疫介导的,PRA分析能反映受者人类白细胞抗原(HLA)的致敏状态,在移植前预测排斥反应的发生和移植后预警移植物丧失,使器官移植后各种排斥反应的发生率显著降低。目前PRA尤其是特异性抗供者抗体(DSA)在肾、心脏、肺等实体器官移植中的作用及其前瞻性应用研究成为热点。本文就PRA与器官移植的研究进展进行综述。     

Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia

A new family of Ig domain receptors referred to as the immune receptor translocation-associated (IRTA) proteins, FcR homologs (FcRHs) or FcR-like that are expressed in lymphoid cells has been recently described. RNA expression analysis suggests that FcRH1-5/IRTA1-5 are expressed exclusively in subsets of the B-cell compartment. We generated mAbs to FcRH1-5/IRTA1-5 and examined their protein expression pattern in normal tissue and in chronic lymphocytic leukemia (CLL) cells. Our data indicated that FcRH1-5/IRTA1-5 were expressed in B-cell sub-populations; however, in some cases, the protein was not expressed in the same B-cell populations as suggested by the RNA expression analysis. FcRH1/IRTA5 was expressed throughout the B-cell lineage starting at the pro-B-cell stage but was down-regulated in plasma cells. FcRH2/IRTA4 was expressed preferentially in memory B cells. FcRH3/IRTA3 was expressed at low levels in naive, germinal center (GC) and memory B cells but was also expressed in NK cells. FcRH4/IRTA1 was expressed in a sub-population of memory B cells associated with mucosal tissue. FcRH5/IRTA2 was expressed in mature B cells and memory B cells and down-regulated in GC cells and, unlike all other B-cell-specific markers, maintained its expression in plasma cells from tonsil, spleen and bone marrow. We examined the expression of FcRH1-5/IRTA1-5 on the surface of CLL cells and found a similar pattern of expression on CLL cells as in the normal mature B cells, except for FcRH3/IRTA3 which was up-regulated in CLL.     

耳塞和眼罩对重症监护室患者谵妄和睡眠质量影响的Meta分析

背景　睡眠问题已成为危重患者普遍存在的问题。低质量的睡眠不仅会增加危重患者的焦虑,还可能导致谵妄等认知功能障碍。药物治疗虽能促进患者睡眠,但也产生一系列的不良反应。因此,采用非药物干预刺激感官知觉和产生放松效果缓解疾病越来越重要。耳塞和眼罩能否改善危重患者的睡眠质量、减少谵妄尚无充足证据支持。目的　评价耳塞和眼罩对重症监护室（ICU）患者谵妄和睡眠质量的影响。方法　计算机检索PubMed、Medline、CINAHL、Cochrane Library、中国知网、万方数据知识服务平台、中国生物医学文献服务系统中ICU患者睡眠相关的文献,试验组给予耳塞和/或眼罩,对照组为空白对照或仅给予常规护理,检索时间为建库至2018年3月。对纳入文献进行质量评价和数据提取,采用RevMan 5.3软件进行Meta分析。结果　共纳入20篇文献,包括1 364例患者。Meta分析结果显示,试验组谵妄发生率低于对照组〔相对危险度（RR）=0.52,95%CI（0.41,0.66）,P<0.000 01〕。试验组匹兹堡睡眠质量量表（PSQI）评分低于对照组〔均数差（MD）=-4.63,95%CI（-6.82,-2.43）,P<0.000 1〕。试验组睡眠有效性评分高于对照组〔标准化均数差（SMD）=1.54,95%CI（0.48,2.61）,P=0.005〕;试验组睡眠障碍评分高于对照组〔SMD=1.36,95%CI（0.55,2.17）,P=0.001〕;两组睡眠补充评分比较,差异无统计学意义〔SMD=1.25,95%CI（-0.34,2.83）,P=0.12〕;两组睡眠时长比较,差异无统计学意义〔SMD=1.11,95%CI（-0.43,2.65）,P=0.16〕;两组睡眠时长的分布比较,差异无统计学意义〔RR=1.00,95%CI（0.76,1.31）,P=1.00〕。结论　耳塞和眼罩可减少ICU患者谵妄发生,并改善其睡眠质量,但对睡眠时长的效果尚不明确。