Aztreonam/Clavulanic Acid in the Treatment of Serious Infections Caused by Stenotrophomonas maltophilia in Neutropenic Patients: Case Reports

Abstract

Two seriously neutropenic patients (a 23-year-old man with a promyelocytic acute myeloid leukemia [AML-M3] and a 77-year old male with an immature acute myeloid leukemia [AML-M1] diagnosis) with severe infections caused by Stenotrophomonas maltophilia were treated with aztreonam/clavulanic acid (2:1) combination. In the first patient the infection was caused by a multiresistant strain and in the second, by a strain with poor response to trimethoprim-sulfamethoxazole and other antimicrobial agents. After treatment with aztreonam/clavulanic acid both patients evolved favorably.     

贵州农村新生儿溶血症群体技术干预效果示范研究

目的:探索贵州农村新生儿溶血症群体干预的有效策略和方法。方法:采用人群预防实验研究方法,在干预县建立示范区,引入新生儿溶血症干预技术进行一年的现场干预。通过对实验区和对照区地区间及干预前后的结果比较,了解新生儿溶血症干预的实施效果。结果:研究共纳入15 795名计划怀孕或已孕妇女作为研究对象,开展新生儿溶血症干预研究,其中干预组8 216人,对照组7 579人;开展血型筛查7 762人,筛查率94.47%;发现高危夫妇659对,其中怀孕615人;开展高危对象孕期B超监测603人,监测率98.05%;高危孕妇血清IgG抗A(B)效价92例;产后访视高危对象615名,访视率100.00%;干预组未发生因新生儿溶血症和母子血型不合高胆红素血症死亡病例,对照组因新生儿溶血症死亡2例,母子血型不合高胆红素血症死亡1例。结论:群体干预技术能够明显降低新生儿溶血症发病率。     

胃癌全胃切除术后肠内营养支持的护理效果分析

目的探讨分析胃癌全胃切除术后肠内营养支持的护理效果。方法选取2013年3月~2014年3月到我院进行胃癌全胃切除术患者共60例,按照随机方法分成观察组和对照组,每组30例。观察组实施肠内营养,对照组患者实施肠外营养,观察患者血总蛋白、白蛋白及血红蛋白三个营养指标的变化。结果两组患者在治疗前TP、Alb、Hb水平差异无统计学意义(P0.05),治疗一周后,两组患者的TP、Alb、Hb水平均明显高于治疗前,且观察组的上升幅度显著高于对照组,差异均有统计学意义(P0.05)。结论胃癌全胃切除术后肠内营养支持不仅可以给患者提供营养,还可以促进肠道功能的快速恢复,降低并发症发生率,有利于患者的早日康复。     

医用化学教学改革探索

根据医用化学授课的多年经验,结合在医用化学教学改革中的一些尝试,提出了着重从激发学生的学习兴趣、精心准备多媒体教学、尝试开展双语授课、积极上好讨论课等四个方面来提高医用化学的教学效果,收效显著。     

我国9城市10386例健康成人肺功能影响因素的相关性分析

目的 调查我国健康成人肺功能的影响因素.方法 采用随机、分层和整群抽样方法,于2008至2011年间对沈阳市、北京市、朝阳市、抚顺市、鞍山市、本溪市、成都市、广州市、上海市9城市18个社区10 386人进行统一的问卷调查、体格检查,并进行肺功能检查.不同性别、年龄、身高、体质量、吸烟情况、被动吸烟情况的比较采用双向相关分析.结果 男性FEV1及FVC明显高于女性(r值分别为0.497、-0.261;P＜ 0.05),但FEV 1/FVC低于女性(r=0.037;P＜0.05);随年龄增大,FEV1、FVC、FEV1/FVC逐渐下降(r值分别为-0.463、-0.426、-0.047;P＜ 0.05);身高增加则FEV1、FVC、FEV1/FVC增大(r值分别为0.320、0.298、0.036;P＜ 0.05);吸烟量(包/年)越大,FEV1、FVC值越大(r值分别为0.021、0.034;P＜0.05),FEV1/FVC越小(r=-0.024;P＜ 0.05).体质量及被动吸烟情况与FEV1、FVC、FEV1/FVC无明显相关性(P＞0.05).吸烟对肺功能的影响上,56～60岁、81～85岁时吸烟与FEV1/FVC呈负相关(r分别为-0.062、-0.200,P＜ 0.05);71～75岁吸烟与FEV1呈负相关(r=-0.076,P=0.022).结论 健康成人肺功能水平受吸烟影响,应避免长期大量吸烟.     

Cross-neutralization between vaccine and circulating wild-type mumps viruses in Korea

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12–15 months and 4–6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1–2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4–5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.     

带中心孔植入式透镜（V4c-ICL）矫正高度近视的视觉质量研究

目的　观察高度近视患者植入带中心孔植入式透镜（implantable collamer lens，ICL）后的临床疗效和视觉相关的生活质量。方法　前瞻性病例研究。选取我院诊断为高度近视，并植入V4c-ICL患者25例（50眼）为研究对象。术前及术后1个月、3个月、6个月分别检查患者屈光状态，裸眼远、中、近视力，最佳矫正远视力，远视力矫正下中、近视力，双眼视力，眼压，角膜内皮细胞密度（corneal endothelial cell density，ECD），并进行国家眼科研究所视功能问卷-25（national eye institute-visual function questionnaire，NEI-VFQ-25）调查及评分。结果　高度近视患者植入V4c-ICL后不同时间球镜、柱镜、等效球镜（spherical equivalent，SE）度较术前均明显降低（F=884.35、17.15、810.25，均为P＜0.05）；术后不同时间裸眼远、中、近视力，最佳矫正远视力，远视力矫正下中、近视力和双眼视力较术前均明显改善（F=604.47、878.13、713.92、22.25、5.33、6.90、16.51，均为P＜0.05）。术前及术后随访期间眼压、ECD无明显变化（F=0.07、1.53，均为P＞0.05）；术后NEI-VFQ-25评分较术前明显提高（F=21.76，P＜0.05）。结论　高度近视患者植入V4c-ICL后屈光不正得到矫正、短期内屈光稳定，随访期间远、中、近视力明显提高，视觉相关的生活质量明显改善。V4c-ICL植入术治疗高度近视安全、有效。     

胶类中药的特点及现代研究分析

动物胶类药物在很多疾病的治疗和保健中发挥重要作用。许多古籍中均有以胶类入方治疗疾病的记载。近年来，胶类药物的相关研究逐渐增多，应用领域也在不断扩大。笔者通过对常用胶类药物的发展变化、药性归经、现代药理作用、临床应用、胶类新药开发前景、质量控制方法等方面的分析总结，整理出胶类中药的发展变迁及现代研究进展，为今后胶类药物的开发利用提供参考。     

抗血小板聚集治疗在大面积脑梗塞中的应用分析

目的探讨抗血小板聚集对大面积脑梗塞进行治疗的临床效果。方法选取100例大面积脑梗塞患者作为研究对象,并将其随机列入观察组和对照组,各50例。观察组应用抗血小板聚集进行治疗,对照组行常规治疗。对比分析两组的疗效。结果观察组的总有效率、神经功能的缺损积分以及日常生活能力的恢复情况均显著优于对照组(P0.05)。结论应用抗血小板聚集对大面积脑梗塞患者进行治疗,疗效确切,安全性强。     

Genome-wide shifts in climate-related variation underpin responses to selective breeding in a widespread conifer

Locally adapted temperate tree populations exhibit genetic trade-offs among climate-related traits that can be exacerbated by selective breeding and are challenging to manage under climate change. To inform climatically adaptive forest management, we investigated the genetic architecture and impacts of selective breeding on four climate-related traits in 105 natural and 20 selectively bred lodgepole pine populations from western Canada. Growth, cold injury, growth initiation, and growth cessation phenotypes were tested for associations with 18,600 single-nucleotide polymorphisms (SNPs) in natural populations to identify “positive effect alleles” (PEAs). The effects of artificial selection for faster growth on the frequency of PEAs associated with each trait were quantified in breeding populations from different climates. Substantial shifts in PEA proportions and frequencies were observed across many loci after two generations of selective breeding for height, and responses of phenology-associated PEAs differed strongly among climatic regions. Extensive genetic overlap was evident among traits. Alleles most strongly associated with greater height were often associated with greater cold injury and delayed phenology, although it is unclear whether potential trade-offs arose directly from pleiotropy or indirectly via genetic linkage. Modest variation in multilocus PEA frequencies among populations was associated with large phenotypic differences and strong climatic gradients, providing support for assisted gene flow polices. Relationships among genotypes, phenotypes, and climate in natural populations were maintained or strengthened by selective breeding. However, future adaptive phenotypes and assisted gene flow may be compromised if selective breeding further increases the PEA frequencies of SNPs involved in adaptive trade-offs among climate-related traits.

Local adaptation of climate-related traits in widespread temperate conifers has been demonstrated for centuries using extensive long-term common garden experiments (1, 2). As early as the 17th century, foresters were instructed to recognize variation in desirable traits and select seed from trees with favorable phenotypes (3). Modern tree improvement programs systematically select upon genetic variation, primarily to achieve growth gains and meet economic objectives. Estimates of genetic variation and gains from selection made using quantitative genetic models assume many anonymous loci of small effect underlie both variation in continuously distributed phenotypes and their responses to selective breeding. However, the type, quantity, effect size, distribution, and dynamics of genes underlying locally adaptive phenotypic variation and responses to selective breeding in forest trees are still poorly understood (4).Directional selection over hundreds or thousands of generations has led to genomic features of domestication in agricultural crops including simplified genetic architectures underlying many traits, reduced genome-wide diversity, and numerous selective sweeps (5–7). Beyond high-gain, short-rotation clonal forestry [e.g., Eucalyptus spp. (8)], we know little about the effects of artificial selection on adaptive genetic variation in forest trees, yet many tree species undergo some degree of selective breeding. Two or three generations of conifer breeding is not expected to have the same magnitude of genetic effects seen in domesticated crops, but if artificial selection for increased productivity is detectable in conifer genomes, it may expose genetic relationships and potential sources of trade-offs between growth and climatically adaptive phenotypes.Climate-related adaptive traits are often intercorrelated due to pleiotropy, natural selection, or linkage disequilibrium (LD), so that strong directional selection on one trait can cause correlated responses in others. Pleiotropic allelic variants associated with phenotypes do not function in isolation. Antagonistic pleiotropic effects among traits can generate adaptive trade-offs among traits within populations, and limit gains from selection on a focal trait (9). Trait–trait correlations can also arise through strong selection acting in parallel on unlinked loci or from LD mediated by physical linkage of loci on chromosomes. Average genome-wide LD estimates in conifers appear to be low (10, 11) but may be greater (r² of 0.2–0.4) within genes under strong selection (12).Conifer studies have identified putatively adaptive phenotype-associated alleles on a locus-by-locus basis using quantitative trait loci (QTL) mapping or genotype–phenotype associations (GPAs) (also known as genome-wide association studies [GWAS]) (13). Genotype–environment association analyses in conifers have identified putatively adaptive environmentally associated loci (e.g., 14, 15), but loci are usually anonymous relative to adaptive phenotypes. All of these approaches are biased toward detecting loci with large phenotypic effects, but expectations that genome scans will discover individual adaptive loci with large effects or frequency differences among populations may be biologically and statistically unrealistic (16, 17). Conifer GPA studies typically detect relatively few statistically significant loci, and locus-by-locus analyses are insufficient to characterize adaptive genome-wide variation associated with adaptive traits and signatures of selective breeding. Multilocus tests for adaptive polygenic signatures of selection have been developed (e.g., refs. 18 and 19), but significant limitations remain (reviewed in refs. 20 and 21).Uncertainty about the effects of selective breeding on adaptive genetic variation is layered upon expectations that forest trees will become maladapted as climates shift (22). Efforts are being made to estimate maladaptation using genome-wide variation associated with adaptive traits and climate (23, 24), because conserving, managing, and efficiently redeploying genetic variation associated with adaptive phenotypes will be a necessary element of strategies to mitigate the effects of shifting climates on forest resources (25). Assisted gene flow strategies in temperate and subboreal forests generally aim to move trees to cooler climates in anticipation of future warming, but trees must then contend with the increased short- to medium-term risk of maladaptation to damaging frost. This means cold tolerance is, perhaps surprisingly, an important trait when planning for warming climates.Genetic approaches have the potential to efficiently and accurately characterize local adaptation to climate. Understanding whether this potential can be realized in a technically robust and operationally feasible way, and whether selection for faster growth compromises genetic variation associated with phenotypic adaptation to climate, has far-reaching implications for developing effective assisted gene flow strategies that mitigate negative climate change impacts on forest health and timber production (26, 27). In this context, our research objectives are to 1) identify the genetic architecture of climate-related adaptive traits in interior lodgepole pine (Pinus contorta Dougl. ex Loud. var. latifolia Engelm.); 2) identify genome-wide effects of artificial selection for increased productivity on climate-related traits; and 3) assess the implications of genetic responses to selection for assisted gene flow strategies.Our study combines climatic data, genotype data from ∼50,000 lodgepole pine single-nucleotide polymorphisms (SNPs), and seedling phenotypic data for height, cold injury, growth initiation, and growth cessation traits. These data were collected from a seedling common garden that sampled reforestation seed lots from 105 natural populations and 20 breeding populations from across the species’ range in Alberta (AB) and British Columbia (BC), Canada (Fig. 1 and SI Appendix, Table S1). For each of the four traits, we identify range-wide GPAs using 929 seedlings from all 105 natural populations. Then for the 1% most strongly phenotype-associated SNPs, we examine how artificial selection within breeding populations has changed allele frequencies at individual SNP loci, within individual seedlings, populations (breeding zones), and three climatic regions (Fig. 1). Using elements from the approach of Turchin et al. (18), we study changes in frequency of the alleles that have a positive effect on adaptive traits (positive effect alleles [PEAs]). At each SNP locus, a PEA is the allele associated with increasing numeric values of the respective phenotype, determined in this case through GPA analyses in the natural seedling populations. PEAs reported here are associated with greater seedling height, greater cold injury, delayed growth initiation, and delayed growth cessation. To parse physical genetic linkage from allelic associations due to other causes, we compare LD estimated from our natural seedlings with estimates of recombination among haploid megagametophytes from a single maternal parent, where physical linkage is the only cause of LD. Integrating genetic, climatic, and phenotypic data gives us a robust basis to detect the effects of artificial selection on climate-related genotypes that are relevant to breeding and assisted gene flow strategies.Open in a separate windowFig. 1.Geographic origins of the natural and selected seedling populations sampled from across the range of lodgepole pine in Alberta (AB) and British Columbia (BC). Natural populations are represented by filled circles; selected seedling breeding zones are represented by filled polygons. The three climatic regions we used were AB, BC-Central, and BC-South. AB breeding zones are formally identified as A, B1, B2, C, J, and K1. BC-Central breeding zone abbreviations are as follows: BV, Bulkley Valley; CP, Central Plateau; and PG, Prince George. BC-South breeding zone abbreviations are as follows: EK, East Kootenay; NE, Nelson; and TO, Thompson–Okanagan. Reprinted from ref. 35, with permission from Elsevier.