不同剂量普奈洛尔治疗婴儿血管瘤的疗效评价

目的：探讨不同剂量普奈洛尔治疗婴儿混合型和深层血管瘤的临床效果，为血管瘤的治疗提供理论和实验依据。方法：将入选的62例混合型和深层血管瘤患儿随机分为普奈洛尔低剂量组和高剂量组，每组31例，分别采用1.5和3.0 mg.kg-1?d-1普奈洛尔口服，每日3次，疗程6个月，动态观察血管瘤的体积变化及不良事件发生率。结果：根据Achauer 疗效判定标准进行疗效比较，普奈洛尔低剂量组患儿总有效率为80.65%（其中Ⅰ级 6例，Ⅱ级 9例，Ⅲ级 11例，Ⅳ级5例)，普奈洛尔高剂量组患儿总有效率为93.55%(其中Ⅰ级 2例，Ⅱ级4例，Ⅲ级 10例，Ⅳ级15例)，普奈洛尔高剂量组疗效优于低剂量组(P<0.01)。不同部位和不同类型血管瘤疗效比较差异均无统计学意义(P>0.05)。2组患儿不良事件发生率比较差异无统计学意义(P>0.05)。 结论：普奈洛尔3.0 mg?kg-1?d-1口服治疗婴儿混合型和深层血管瘤疗效明显增加，但不良反应未见增加。建议临床治疗婴儿血管瘤时，可提高普奈洛尔的剂量，以提高治疗效果。     

生物过滤除臭法在渗沥液处理工程中的应用

介绍了生物过滤除臭法的优点和原理、生物滤池除臭系统及其工艺流程。以郑州市垃圾综合处理厂渗沥液处理扩建工程为例,阐述了工程中选用生物过滤除臭法的原因,并对除臭设备进行选型计算,分析了除臭设备的运行效果。     

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.     

腹腔镜下与开腹子宫肌瘤剔除术的临床效果与并发症对比分析

目的:通过对比分析的方法探讨腹腔镜与开腹手术在子宫肌瘤剔除术中的临床效果与并发症情况。方法:选取2013年3月至2014年6月子宫肌瘤患者共156例,随机分为对照组和研究组,每组各78例。其中对照组采用传统开腹手术进行治疗,研究组采用腹腔镜手术的治疗方法,对比两组患者的临床治疗效果和并发症情况。结果:两组患者的手术时间无显著差异(P0.05),术中出血量、住院时间及术后排气时间情况研究组均明显优于对照组(P0.05);研究组患者的并发症发生率明显低于对照组(P0.05)。结论:腹腔镜用于治疗子宫肌瘤具有良好的临床治疗效果,能够减少治疗对患者造成的创伤,提高患者治疗体验并能有效降低并发症发病率,值得在临床上进行推广。     

Molecular xenomonitoring and host identification of Leishmania sand fly vectors in a Mediterranean periurban wildlife park

The epidemiological cycle of zoonotic phlebotomine‐borne Leishmania infantum is a complex system in which domestic animals and wildlife interact and participate in its maintenance and transmission. In this study, we combined entomological surveillance, xenomonitoring of L. infantum and identification of host feeding sources of engorged females to investigate the potential contribution of a periurban wildlife park to leishmaniosis in neighbouring residential areas. Overall, 7,309 sand flies were collected in 111 trap‐days during the summers of 2016–2018 in an endemic area in south‐east Spain. Five different sand fly species were captured, with Phlebotomus perniciosus, the main L. infantum vector in this region, representing the most common species. Sand fly distribution was spatially heterogeneous in terms of species, sexes and female physiological stage (unfed, gravid and engorged females) and related to host distribution and management, and environmental features. None of the 602 sand flies analysed for L. infantum infection by kinetoplast real‐time PCR were positive. We used molecular tools to identify the vertebrate hosts of sand flies and identified 17 host species, mainly mammals. Human DNA was not identified in engorged sand flies. This study provides evidence that wildlife parks in south‐east Spain are ideal grounds for sand fly vectors but do not necessarily increase L. infantum infection risk to humans and dogs living in surrounding residential areas. This is probably because vectors feed mostly on non‐L. infantum competent hosts and this should be investigated for a better understanding of the contribution of wildlife parks to the local epidemiology of L. infantum.     

浙江省德清县县域医共体改革措施与效果分析

目的：分析浙江省德清县县域医共体改革措施及阶段性成效。方法：定性访谈了解医共体整合措施，定量分析医共体建设前后（2016-2018年）各级医疗机构医疗服务利用数据及医共体部分绩效考核数据。结果：医共体在组织、管理、功能、服务方面进行整合，并取得阶段成效：医保基金在县域内支出率有所增加；乡镇卫生院卫生人员数量、医疗收入有所提高，乡镇卫生院住院病人人均医药费有所降低。结论：医共体取得初期成效，应开展以患者健康结局指标为主的长期追踪调查，全面系统评估医共体；保留基层医疗机构地位、功能定位不变；探索实行医共体"总额预付、结余奖励"制度，将医共体发展成以患者健康为中心、基于利益共享机制、分工合作的责任利益共同体。     

Nicotine does not affect stem cell properties requisite for suicide gene therapy against glioma

ABSTRACT

Objective: 

Glioblastoma is one of the most lethal tumors in adult central nervous system with a median survival of a year and half and effective therapeutic strategy is urgently needed. For that reason, stem cell-based suicide gene therapies have attracted much interest because of potent tumor tropism of stem cells and bystander effect. In this current clinical situation, stem cells are promising delivery tool of suicide genes for glioma therapy. Since habitual cigarette smoking still prevails worldwide, we investigated the effect of nicotine on stem cell tropism toward glioma and gap junctional intercellular communication (GJIC) function between glioma and stem cells, both of which are important for suicide gene therapies. Methods: Mouse induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) and human dental pulp mesenchymal stem cells (DPSCs) were used. The effect of nicotine on tumor tropism to glioma-conditioned medium (CM) at a non-cytotoxic concentration was assessed with Matrigel invasion assay. Nicotine effect on GJIC was assessed with the scrape loading/dye transfer (SL/DT) assay for co-culture of glioma and stem cells and the parachute assay among glioma cells using high-content analysis. Results: Tumor tropism of iPS-NSCs toward GL261-CM and DPSCs toward U251-CM was not affected by nicotine (0.1 and 1 µM). Nicotine at the concentrations equivalent to habitual smoking (1 µM) did not affect GJIC of iPS-NSC/GL261 and DPSC/U251 and GJIC among each glioma cells. Conclusions: The study demonstrated that non-cytotoxic concentrations of nicotine did not significantly change the stem cell properties requisite for stem cell-based suicide gene therapy.     

The link between language and action in aging

ObjectiveMany studies have demonstrated the existence of a link between action verb processing and action. However, little is known about the changes in this relationship with aging.MethodTo assess this point, we compare the performances of younger and older people during a priming task consisting of judging whether an image contains a human after listening to an action verb.ResultsIn accordance with previous literature, the results showed that younger people were faster to detect the presence of a human in the image in congruent conditions, namely, when the action verb and the image refer to the same action. However, this effect was not present in older adults’ participants.ConclusionThese findings suggest that the link between action and language decreases with age. We discuss these findings in the context of the embodied view of cognition.     

整脊推拿结合化痰祛瘀方治疗颈源性眩晕伴颈动脉斑块43例

目的:观察整脊推拿结合中药化痰祛瘀方治疗颈源性眩晕伴颈动脉斑块的的效果及安全性。方法:伴有颈动脉斑块的颈源性眩晕患者按随机数字表法分为两组,对照组45例采用基础治疗联合中药化痰祛瘀方,观察组43例在对照组基础上结合整脊推拿干预,治疗后统计比较两组眩晕指征和血脂改善情况。结果:治疗后两组患者眩晕、耳鸣、恶心欲呕、头痛、视力障碍、猝倒发作、颈项不适、反应迟钝等症状的恢复率比较,差异有统计学意义(P<0.01);治疗结束后观察组的总有效率为95.35%,明显优于对照组的77.78%,差异有统计学意义(P<0.05);疗程结束后两组患者血脂均较治疗前有所改善(P<0.05),观察组中的总胆固醇(TC)、低密度脂蛋白(LDL)明显低于对照组,高密度脂蛋白(HDL)明显高于对照组,差异均有统计学意义(P<0.05),但三酰甘油(TG)和对照组比较差异无统计学意义(P> 0.05)。结论:整脊推拿结合化痰祛瘀方治疗颈源性眩晕伴颈动脉斑块,在改善眩晕相关指征和血脂方面疗效较好。