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.     

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.     

Successful reproduction of adenoviral gizzard erosion in 20-week-old SPF layer-type chickens and efficacious prophylaxis due to live vaccination with an apathogenic fowl adenovirus serotype 1 strain (CELO)

Recently, outbreaks of adenoviral gizzard erosion (AGE) have been documented in pullets and layers housed free range and in enriched cage systems characterized by increased mortality and a negative impact on egg production. In the present study the pathogenicity of a fowl adenovirus serotype 1 (FAdV-1) field strain as well as the aetiological role of a FAdV-8a strain, both isolated from AGE affected pullets, were investigated in vivo in 20-week-old specific-pathogen-free (SPF) layer-type chickens. Furthermore, the efficacy of a single (week 17) and double (week 14 and 17) application of a live vaccine consisting of an apathogenic FAdV-1 (CELO strain) against challenge with virulent FAdV-1 was investigated.For the first time, AGE was successfully reproduced in adult birds after oral infection of 20-week-old SPF birds with a virulent FAdV-1 field isolate, characterized by pathological changes of the gizzard from 7 days post challenge onwards. In addition, a negative impact of the FAdV-1 infection on the development of the reproductive tract was observed. Thus, confirming the pathogenicity and aetiological role of FAdV-1 in the development of AGE and economic losses due to AGE in layers. In contrast, no pathological changes were observed in birds infected with FAdV-8a.Independent of a single or double application of the live FAdV-1 vaccine strain CELO, no gross pathological changes were observed in gizzards post challenge with the virulent FAdV-1, indicating that complete protection of layers against horizontal induction of AGE was achieved. Nonetheless, virulent FAdV-1 was detected in cloacal swabs and gizzards in both vaccinated groups post challenge determined by the application of an amplification refractory mutation system quantitative PCR used to differentiate between vaccine and challenge strains.     

BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity

We examined the impact of pre-existing SARS-CoV-2-specific cellular immunity on BNT162b2 mRNA COVID-19 vaccine reactogenicity. Of 96 healthcare workers (HCWs), 76% reported any vaccine reaction (first dose: 70%, second dose: 67%), none of which was severe. Following first dose, systemic reactions were significantly more frequent among HCWs with past infection than in infection-naïve individuals, and among HCWs with pre-existing cellular immunity than in those without it. The rate of systemic reactions after second dose was 1.7 and 2.0-times higher than after first dose among infection-naïve HCWs and those without pre-existing cellular immunity, respectively. Levels of SARS-CoV-2-specific T-cells before vaccination were higher in HCWs with systemic reactions after the first dose than in those without them. BNT162b2 vaccine reactogenicity after first dose is attributable to pre-existing cellular immunity elicited by prior COVID-19 or cross-reactivity. Reactogenicity following second dose suggests an immunity-boosting effect. Overall, these data may reduce negative attitudes towards COVID-19 vaccines.Study Registration.The study was registered on clinicaltrials.gov, NCT04402827.     

卫生应急服务覆盖程度及其效果：基于辽宁吉林两省的实证分析

目的分析辽宁吉林两省卫生应急服务覆盖程度及其工作效果，为辽宁吉林两省进一步完善突发公共卫生事件应急处置体系提供理论依据。 方法为了保持量化的原则，选取功能服务与公众需要的匹配程度这一具体指标来反映卫生应急服务覆盖程度，系统收集2000至2017年辽宁吉林两省卫生应急服务相关的文件和文献数据，摘录文件中所涉及的卫生应急服务三级预防功能服务的表述；摘录文献中涉及的卫生应急服务工作效果的表述，采用"五分度评分法"判定工作效果；采用Speraman相关、单因素回归方法分析辽宁吉林两省卫生应急服务覆盖范围与辽宁吉林两省工作效果的关系。 结果2017年，辽宁省卫生应急服务覆盖程度达到56.5%，吉林省达到64.7%。辽宁吉林两省卫生应急服务覆盖程度与卫生应急工作效果都呈正相关关系(P均<0.05)，并且吉林省的显著性更强。 结论吉林省在卫生应急服务覆盖程度表现更佳。同时也验证了卫生应急服务覆盖程度量化方法和工作效果评价方法是可行的，可应用于公共卫生的其他领域。     

3种中和剂对常用消毒剂在Vero细胞上的中和效果

 目的  研究0.5%硫代硫酸钠、10%胰蛋白胨大豆肉汤（tryptic soy broth， TSB）培养基、10%Letheen肉汤培养基对实验室常用的4种消毒剂的中和效果，为疫苗生产和检定中科学选择中和剂提供依据。 方法  取生长良好的Vero细胞接种于96孔培养板，每组8个复孔，置于37 ℃、5% CO2培养过夜。将3种中和剂分别与杀孢子剂、0.5%“84”消毒液、酸性苯酸盐、碱性苯酚盐4种消毒剂中和后，接种于单层生长的Vero细胞，显微镜下观察细胞生长情况。结果  0.5%硫代硫酸钠分别与杀孢子剂、0.5%“84”消毒液中和后接种细胞，8孔细胞全部存活；而0.5%硫代硫酸钠分别与酸性苯酚盐和碱性苯酚盐的中和产物接种细胞后，细胞全部死亡。10% TSB培养基分别与酸性苯酚盐、碱性苯酚盐中和后接种细胞，8孔细胞全部存活；而10% TSB培养基分别与杀孢子剂和0.5%“84”消毒液的中和产物接种细胞后，细胞全部死亡。10%Letheen肉汤培养基接种细胞后，8个孔细胞全部死亡。结论  0.5%硫代硫酸钠可中和杀孢子剂和0.5%“84”消毒液的消毒作用，10%TSB培养基可中和酸性苯酚盐和碱性苯酚盐的消毒作用。10%Letheen肉汤培养对Vero细胞有毒性作用。     

Hydroxyurea-induced genital ulcers and erosions: Two case reports

Hydroxyurea is a chemotherapeutic agent used for myeloproliferative disorders and sickle cell anemia that is well known to cause painful mucocutaneous ulcers, typically involving the legs or mouth. However, genital ulcerations due to hydroxyurea therapy are a rare, and likely underrecognized, adverse effect with only a few cases reported in the literature to date. Ulcers of the lower legs caused by hydroxyurea are associated with a diagnostic delay, and this is likely exacerbated in cases of genital ulceration due to a lack of awareness. Herein we present two cases of painful genital ulceration in patients on hydroxyurea therapy. In the first Case, an 87 year-old male with polycythemia vera developed an ulcer on the scrotum, which was assessed initially through virtual visits during the COVID-19 pandemic, and was refractory to topical and oral antibiotic treatments. The second case was a 79 year-old male with essential thrombocythemia and a history of persistent leg ulcers who developed erosions of the glans penis. Both patients experienced complete resolution within weeks of discontinuing hydroxyurea therapy. In conclusion, genital ulcers and erosions induced by hydroxyrea may be underrecognized in clinical practice, but if identified, withdrawal of hydroxyurea leads to quick resolution of these lesions and the associated pain.