ONRAB® oral rabies vaccine is shed from,but does not persist in,captive mammals

ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.     

Genomic targeting by recombinase‐mediated cassette exchange in the spotted wing drosophila,Drosophila suzukii

Drosophila suzukii is a significant pest of stone and small fruits. The genome of this species has been sequenced and manipulated by transposon‐mediated transformation and CRISPR/Cas9 gene editing. These technologies open a variety of possibilities for functional genomics and genetic modifications that might improve biologically based population control strategies. Both of these approaches, however, would benefit from genome targeting that would avoid position effects and insertional mutations associated with random transposon vector insertions, and the limited DNA fragment insertion size allowed by gene editing. Here, we describe an efficient recombinase‐mediated cassette exchange (RMCE) system for D. suzukii in which heterospecific lox recombination sites were integrated into the genome by transposon‐mediated transformation and subsequently targeted for double recombination by a donor vector in the presence of Cre recombinase. Three loxN/lox2272 landing site lines have previously been created in D. suzukii, and quantitative PCR determined that polyubiquitin‐regulated enhanced green fluorescent protein expression is least susceptible to position effect suppression in the 443_M26m1 line. We presume that RMCE target sites may also be inserted more specifically into the genome by homology‐directed repair gene editing, thereby avoiding position effects and mutations, while eliminating restrictions on the size of donor constructs for subsequent insertion.     

Identification of microbes in wounds using near-infrared spectroscopy

BackgroundRapid diagnosis of microbes in the burn wound is a big challenge in the medical field. Traditional biochemical detection techniques take hours or days to identify the species of contaminating and drug-resistant microbes. Near-infrared spectroscopy (NIRS) is evaluated to address the need for a fast and sensitive method for the detection of bacterial contamination in liquids.MethodsHerin, we developed a novel technique which by using NIRS together with supporting vector machine (SVM), to identify the microbial species and drug-resistant microbes in LB medium, and to diagnose the wound colonization and wound infection models of pigs.ResultsThe device could recognize 100% of seven kinds of microbes and 99.47% of the multi-drug resistant Staphylococcus aureus (S. aureus), with a concentration of 10⁹ cfu ml^?1 in LB medium. The accuracy of the microbial identification in colonized and infected wounds in-situ was 100%. The detection limit of NIRS with SVM for the detection of S. aureus and Escherichia coli (E. coli) was 10¹ cfu ml^?1 in LB medium. Identification time was less than 5 s.ConclusionOur findings validate for the first time a novel technique aimed at the rapid, noncontacted, highly sensitive, and specific recognition of several microbial species including drug-resistant ones. This technique could represent a promising approach to identify diverse microbial species and a potential bedside device to rapidly diagnose infected wounds.     

口语化疾病名称向国际规范疾病术语集的映射研究

目的：研究患者口语化疾病名称到术语疾病名称的映射，解决在线口语化疾病名称难以有效利用的问题。方法：抓取“微医网”上患者口语中的疾病名，将PubMed摘要、百度搜索页摘要与百科内容作为语料，训练词向量，用余弦距离计算相似度，由2名具有临床知识和从业经验的编码人员对结果的准确性进行检验。结果：将最相似词条的参数TopN设置为>= 30的时候效果比较好，映射到大类和细类的准确性分别稳定在60%和70%左右。结论：利用词向量将口语化疾病名称映射到国际疾病术语集，具有较强的通用性和可行性，对于在线问诊、智能分诊甚至自动化编码具有明显的参考借鉴价值。     

HSP90β干扰和过表达慢病毒载体的构建及其在骨肉瘤细胞Saos-2中的表达

目的:获得热休克蛋白90β(HSP90β)基因干扰和过表达慢病毒表达系统，并检测其在人骨肉瘤细胞株Saos-2中的表达水平。方法:设计合成shRNA，以慢病毒表达质粒构建HSP90β干扰和过表达载体，酶切电泳、测序技术鉴定载体构建是否成功。重组病毒转染H1299细胞，以嘌呤霉素筛选稳定转染的Saos-2细胞，通过荧光显微镜观察计数获得转染效率。将感染好的细胞分为干扰NC组（NEG-shRNA）、干扰组（shRNA-HSP90β）、过表达NC对照组（NEG-pEZ）及过表达组（pEZ-HSP90β）。通过qRT-PCR 与Western blotting 分别从mRNA 和蛋白表达水平验证目的基因的干扰和过表达水平。结果:插入慢病毒表达载体的基因片段与目的基因的碱基序列完全一致。病毒包装成功后，嘌呤霉素最小致死浓度1 μg/ml，感染复数200，感染人Saos-2的感染效率达80%，其中shRNA-HSP90β组干扰效率为86.35%，pEZ-HSP90β组的mRNA相对表达量增加2.8倍。进一步研究发现，shRNA-HSP90β组较NEG-shRNA组中HSP90β蛋白表达明显降低，pEZ-HSP90β组较NEG-pEZ组HSP90β蛋白表达增加。结论:HSP90β基因干扰和过表达慢病毒载体构建成功，并能够在Saos-2中稳定表达。     

机器学习算法在麻醉领域的应用

人工智能在医疗领域的应用逐步推动医疗变革,机器学习算法融入麻醉领域对于进一步提升麻醉发展意义重大。为了解机器学习算法在麻醉领域的应用现况及推动相关研究进展,本文总结了机器学习在围手术期麻醉管理和预测术后并发症方面的应用、基本概念和研究现状,指出了目前机器学习算法在医疗领域的不足之处。     

Reduced regional homogeneity and neurocognitive impairment in patients with moderate-to-severe obstructive sleep apnea

BackgroundNeurocognitive dysfunction and abnormal regional homogeneity (ReHo) have been reported in patients with obstructive sleep apnea (OSA). However, little is known about whether brain functional alteration could be used to differentiate from healthy controls (HCs) and its correlation with neurocognitive impairment.MethodsThirty-three treatment-naive patients with moderate-to-severe OSA and 22 HCs with matched age, sex and education underwent the evaluation of Epworth sleepiness scale, neurocognitive function, full night polysomnography and resting-state functional magnetic resonance imaging scan. ReHo, support vector machine, and correlation with neurocognitive function were administrated to analyze the data.ResultsCompared with HCs, patients with OSA showed decreased ReHo in the bilateral superior frontal gyrus (FG), bilateral superior medial prefrontal cortex (PFC)/right supplementary motor area (SMA), left middle FG, and right precentral/postcentral gyrus. Negative correlations were observed between the ReHo values in the left superior FG/middle FG and apnea hypopnea index, oxygen desaturation index in the OSA group. The scores of Stroop word test, Stroop color-word test, symbol coding test were all negatively correlated with the ReHo values in the right precentral gyrus/postcentral gyrus in patients. Scores of the animal naming fluency test were positively correlated with the ReHo values in the left superior FG/middle FG in patients. Moreover, support vector machine analysis showed the ReHo values in the left superior FG/middle FG or bilateral superior medial PFC/right SMA both could discriminate patients from HCs with good accuracies, sensitivities, and specificities (85.45%, 87.88%, 81.82% and 81.82%, 84.85%, 77.27%, respectively).ConclusionDysfunction in the frontal lobe is a potentially pivotal neuro-pathophysiological mechanism of neurocognitive impairment in patients with moderate-to-severe OSA. And significantly lower ReHo values in the left superior FG/middle FG and/or superior medial PFC/SMA are promising imaging biomarkers to discriminate moderate-to-severe patients with OSA from HCs.     

生物电阻抗矢量法评估血液透析合并高血压患者的容量负荷

目的应用生物电阻抗矢量法评估血液透析合并高血压患者的容量负荷,探讨高容量负荷状态对高血压患者预后的影响。方法研究对象来自南京医科大学附属明基医院透析前收缩压(6次透析治疗前平均收缩压值)>160 mmHg的血液透析患者。用生物电阻抗矢量法评估患者容量状态,并根据患者容量状态分为容量增加组和非容量增加组(包括容量正常和容量下降的患者)。比较两组患者临床资料、实验室指标、细胞内液比例(ICW)、细胞外液比例(ECW)、体细胞质量、瘦体重、干瘦体重及其占总体重的百分比、脂肪含量占总体重的百分比、阻抗/身高、容抗/身高、相位角、疾病指数的差异。采用Kaplan⁃Meier生存曲线比较两组患者生存率的差异。结果共51例血液透析合并高血压患者入选本研究,容量增加组19例,非容量增加组32例(容量正常27例,容量下降5例)。容量增加组患者的血白蛋白、前白蛋白、血红蛋白、血细胞比容、血磷较非容量增加组显著下降,淋巴细胞比例明显升高,组间比较差异均有统计学意义(均P<0.05)。容量增加组的细胞外液比例、疾病指数显著高于非容量增加组(均P<0.01);相位角、阻抗/身高、容抗/身高显著低于非容量增加组(均P<0.01)。临床追踪20个月,容量增加组患者血压达标率(透析前收缩压<160 mmHg)低于非容量增加组(26.3%比43.8%),但差异无统计学意义。容量增加组患者全因死亡率高于非容量增加组(26.3%比15.6%),Kaplan⁃Meier生存曲线分析提示两组生存率的差异尚无统计学意义。结论容量负荷增加的血液透析合并高血压患者细胞外液增加明显,营养状态评估指标较非容量增加的高血压患者明显下降,而淋巴细胞比例升高,可能与患者微炎症状态有关。容量负荷增加的高血压患者血压更加难以控制,临床预后可能不及非容量增加的患者。