造血干细胞移植病人极期阴囊处皮肤损伤的护理

白细胞是人体防御细菌入侵的重要防线,中性粒细胞占白细胞总数50%～70%,机体抵御病原体,特别是处于化脓性细菌入侵的第一线,是一道天然免疫屏障。病人极期白细胞及中性粒细胞计数持续下降,一般有头晕、乏力、四肢酸软、食欲减退、低热、失眠或极度衰弱等非特异性症状[1,2]。尤其是病人虚弱多汗,阴囊处皮肤的特性及经钴60全身照射对皮肤的特异性损害,导致阴囊处发生皮肤损伤的几率增加。此期病人易发生     

Characterization of clear cell renal cell carcinoma with diffusion kurtosis imaging: correlation between diffusion kurtosis parameters and tumor cellularity

The aim of this study was to evaluate the role of diffusion kurtosis imaging (DKI) in the characterization of clear cell renal cell carcinoma (ccRCC) and to correlate DKI parameters with tumor cellularity. Fifty‐nine patients with pathologically diagnosed ccRCCs were evaluated by DKI on a 3‐T scanner. Regions of interest were drawn on the maps of the mean diffusion coefficient (MD) and mean diffusion kurtosis (MK). All ccRCCs were histologically graded according to the Fuhrman classification system. Tumor cellularity was measured by the nuclear‐to‐cytoplasm (N/C) ratio and the number of tumor cell nuclei (NTCN). ccRCCs were classified as grade 1 (n = 23), grade 2 (n = 24), grade 3 (n = 10) and grade 4 (n = 3). Both MD and MK could readily discriminate between normal renal parenchyma and ccRCCs (p < 0.001), and receiver operating characteristic (ROC) curve analysis showed that MK exhibited a better performance with an area under the ROC curve of 0.874 and sensitivity/specificity of 68.33%/100% (p < 0.001). Further, MD and MK were significantly different between grade 1 and grades 3 and 4 (p = 0.01, p < 0.001) and between grade 2 and grades 3 and 4 (p = 0.015, p < 0.005), respectively. However, no significant difference was found between grade 1 and grade 2 (p > 0.05) for both MD and MK. With regard to NTCN, no significant difference was found between any two grades (p > 0.05), and the N/C ratio changed significantly with grade (p < 0.01, between any two grades). Negative correlations were found between MK and MD (r = –0.56, p < 0.001), and between MD and N/C ratio (r = –0.36, p < 0.005), whereas MK and the N/C ratio were positively correlated (r = 0.45, p = 0.003). DKI could quantitatively characterize ccRCC with different grades by probing non‐Gaussian diffusion properties related to changes in the tumor microenvironment or tissue complexities in the tumor. Copyright © 2016 John Wiley & Sons, Ltd.     

Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease

There is no effective drug to treat Alzheimer’s disease (AD), a neurodegenerative disease affecting an estimated 30 million people around the world. Strongly supported by preclinical and clinical studies, amyloid-beta (Aβ) may be a target for developing drugs against AD. Meanwhile, the fact that localized neuronal death/loss and synaptic impairment occur in AD should also be considered. Neuronal regeneration, which does not occur normally in the mammalian central nervous system, can be promoted by neurotrophic factors (NTFs). Evidence from clinical trials has shown that both Aβ clearance and NTFs are potentially effective in treating AD, thus a new approach combining Aβ clearance and administration of NTFs may be an effective therapeutic strategy.     

Retention and HIV seroconversion among drug users on methadone maintenance treatment in Yunnan,China

Setting: Thirteen methadone maintenance treatment (MMT) clinics across Yunnan, the province with the highest human immunodeficiency virus (HIV) burden in China.Objectives: To determine, among HIV-negative participants on MMT, the proportion lost to follow-up (defined as those who missed the 6-monthly follow-up examination), factors associated with loss to follow-up (LFU), HIV seroconversion rate and factors associated with seroconversion.Design: Prospective cohort study from October 2008 to April 2011. All participants were administered a pre-tested structured questionnaire to capture associated factors and offered HIV testing every 6 months. χ² test and log-binomial regression were used for data analysis.Results: Of 1146 participants, 541 (47%) were lost to follow-up in 2.5 years. Factors associated with higher LFU proportion include <6 months of previous MMT, inconvenient location of the MMT clinic and average methadone dose ⩽60 mg/day, with adjusted relative risks (RRs) of respectively 1.4 (95%CI 1.2–1.5), 1.2 (95%CI 1.0–1.4) and 1.1 (95%CI 1.0–1.3). The overall HIV seroconversion rate was 6.6 (95%CI 3.7–11.0) per 1000 person-years. Not living with a partner contributed to higher HIV rates, with an adjusted RR of 3.6 (95%CI 1.0–12.8).Conclusion: The retention rate of MMT participants in Yunnan was not satisfactory. Decentralising service delivery in the community and making directly observed treatment more convenient has the potential to improve retention.     

UPLC-MS结合网络药理学及实验验证罗欧咳祖帕对哮喘气道重塑的作用

目的 基于超高效液相色谱-质谱联用（UPLC-MS）、网络药理学及实验验证探讨罗欧咳祖帕干预哮喘气道重塑的作用研究。方法 基于UPLC-MS指认罗欧咳祖帕中化学成分信息；借助中药系统药理学数据库和分析平台（TCMSP）的口服利用度（OB）和类药性（DL）、SwissADEM的Lipinski五规则及查阅文献筛选罗欧咳祖帕潜在有效成分；通过SwissTargetPrediction数据库筛选罗欧咳祖帕的成分靶点；利用在线人类孟德尔遗传目录（OMIM）、GeneCards、DrugBank及DisGeNET数据库获取哮喘气道重塑的相关靶点；利用STRING数据库对主要靶点进行蛋白质-蛋白质相互作用（PPI）分析，通过DAVID数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析；最后构建卵蛋白（OVA）诱导小鼠建立哮喘气道重塑模型，采用苏木素-伊红（HE）染色、过碘酸雪夫染色（PAS）染色、马松（Masson）染色观察肺组织病理情况，检测小鼠肺泡灌洗液（BALF）中炎症细胞，并用蛋白免疫印迹法（Western blot）检测小鼠肺组织中蛋白的表达水平，进一步验证关键的信号通路。结果 UPLC-MS检测负离子模式下82个成分，正离子模式下74个成分；通过网络药理学研究共得到罗欧咳祖帕36个候选成分和578个预测靶点，并得到与哮喘气道重塑共同靶点173个，包括癸二酸、柳穿鱼黄素、柚皮素、芹菜素等关键化合物和蛋白激酶B1（Akt1）、低氧诱导因子1α重组蛋白（HIF1A）等潜在的作用靶点；KEGG富集分析预测罗欧咳祖帕主要通过磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）、HIF-1α、丝裂原活化蛋白激酶（MAPK）等信号通路发挥抗哮喘气道重塑作用；动物实验表明，复方可减少哮喘小鼠气道杯状细胞增生，改善气道上皮下胶原沉积情况，降低小鼠因OVA致敏激发而上调的磷酸化（p）-Akt/Akt、HIF-1α的相对表达水平（P<0.05，P<0.01），与网络药理学结果相符。结论 采用UPLC-MS结合网络药理学的方法，初步明确了罗欧咳祖帕的化学组成及其干预哮喘气道重塑的潜在作用机制，罗欧咳祖帕可能通过以Akt1、HIF-1α为代表的核心靶点及以PI3K/Akt、HIF-1α通路为代表的多通路，起到协同干预哮喘气道重塑的作用，为罗欧咳祖帕后续进一步研究提供思路。     

白细胞过滤时机对于血小板输注效果影响的Meta分析

目的 系统评价WBC过滤时机对于血小板(PLT)输注效果的影响.方法 计算机检索Pubmed,EMBASE,Cochrane图书馆和中国生物医学文献数据库,检索年限从建库至2011年12月.纳入比较保存前与保存后过滤WBC的PLT输注效果的临床试验相关文献.采用RevMan 5.0软件进行Meta分析.结果 共纳入4篇相关研究的文献.Meta分析结果显示:与输注保存前过滤WBC的PLT相比,输注保存后过滤WBC的PLT的24 h血小板计数增加校正值(CCI)比较,差异无统计学意义[MD=-0.58,95％CI(-1.75,0.58),P=0.33],不良反应发生率比较,差异无统计学意义[RR=0.76,95％CI (0.56,1.03),P=0.07].结论 WBC过滤时机对于PLT输注后24 h CCI值和不良反应发生率无影响.     

Optimization of voriconazole dosage regimen to improve the efficacy in patients with invasive fungal disease by pharmacokinetic/pharmacodynamic analysis

Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in hospitalized patients. To maximize the efficacy of voriconazole treatment, the study established the relationship between voriconazole pharmacokinetic/pharmacodynamic (PK/PD) and probability of response and optimized voriconazole dosage regimen in patients with IFD based on Monte Carlo simulation. Forty‐four patients proven with IFD were involved in this study. Among them, the overall cure rate was 75% (33/44) and there was a significant difference between C_min/MIC values in patients with lack of response (n = 11) and those with successful response (n = 33) (mean value: 1.91 vs. 11.33; P < 0.05). Logistic regression model showed a high correlation between voriconazole C_min/MIC ratio and clinical response (P = 0.044, OR = 1.349). According to Monte Carlo simulation results under different voriconazole dosing regimens, we could draw a conclusion that 200 mg voriconazole administered intravenously or orally twice daily for Candida infections and 300 mg administered orally or with 200 mg administered intravenously twice daily for Aspergillus infections were rational, which could achieve a value of the cumulative fraction of response >90%. This study built the relationship between voriconazole PK/PD and clinical response and obtained the reasonable empirical dosage regimen, which can be used to customize individual dosage regimen and improve the efficacy of voriconazole treatment.