手足口病患儿外周血单核细胞亚群的研究

目的：探讨未经治疗和随访1、3、5 d手足口患儿外周血单核细胞亚群的变化。方法流式细胞仪检测104例未经治疗手足口患儿（包括阴性患儿62例,EV71阳性患儿37例,CVA16阳性患儿5例）和随访1、3、5 d的患儿外周血单核细胞CD14highCD16-亚群、CD14highCD16＋亚群和CD14lowCD16＋亚群。结果与健康儿童组相比,手足口患儿CD14highCD16＋单核细胞亚群所占总单核细胞比例明显升高（t =4.092,P ＜0.001）;CD14highCD16-亚群比例明显降低。阴性、EV71型、CVA16型患儿之间CD14highCD16-亚群、CD14highCD16＋亚群和CD14lowCD16＋亚群差异均无统计学意义。结论未经治疗的手足口患儿外周血单核细胞亚群的变化可能与EV71及CVA16病毒的持续感染有关,与病毒种类相关性不明显。     

Tinnitus behavior and hearing function correlate with the reciprocal expression patterns of BDNF and Arg3.1/arc in auditory neurons following acoustic trauma

The molecular changes following sensory trauma and the subsequent response of the CNS are poorly understood. We focused on finding a molecular tool for monitoring the features of excitability which occur following acoustic trauma to the auditory system. Of particular interest are genes that alter their expression pattern during activity-induced changes in synaptic efficacy and plasticity. The expression of brain-derived neurotrophic factor (BDNF), the activity-dependent cytoskeletal protein (Arg3.1/arc), and the immediate early gene c-Fos were monitored in the peripheral and central auditory system hours and days following a traumatic acoustic stimulus that induced not only hearing loss but also phantom auditory perception (tinnitus), as shown in rodent animal behavior models. A reciprocal responsiveness of activity-dependent genes became evident between the periphery and the primary auditory cortex (AI): as c-Fos and BDNF exon IV expression was increased in spiral ganglion neurons, Arg3.1/arc and (later on) BDNF exon IV expression was reduced in AI. In line with studies indicating increased spontaneous spike activity at the level of the inferior colliculus (IC), an increase in BDNF and GABA-positive neurons was seen in the IC. The data clearly indicate the usefulness of Arg3.1/arc and BDNF for monitoring trauma-induced activity changes and the associated putative plasticity responses in the auditory system.     

Proteasome-dependent, ubiquitin-independent degradation of Daxx by the viral pp71 protein in human cytomegalovirus-infected cells

The cellular Daxx protein represses human cytomegalovirus (HCMV) gene expression from the major immediate early promoter. HCMV prevents Daxx-mediated silencing during lytic infection by delivering the viral pp71 tegument protein to the nucleus, where pp71 binds to and induces the proteasomal degradation of Daxx. In this study, we show that a functional ubiquitin pathway is not required for the proteasomal degradation of the endogenous Daxx protein by tegument-delivered pp71 in HCMV-infected cells, demonstrating that the pp71-mediated degradation of Daxx occurs through a proteasome-dependent, ubiquitin-independent pathway.     

EV71手足口病患儿CD8~+T、NK细胞穿孔素和颗粒酶B的变化

目的探讨肠道病毒7l型(EV71)手足口病患儿CD8~+T、NK细胞穿孔素(PRF)和颗粒酶B(Grz B)的变化。方法选取某儿童医院2017年5—7月普通型、重型手足口病患儿(普通型组、重型组),健康儿童志愿者(正常对照组)各30例,采用流式细胞术测定外周血CD8~+T、NK细胞PRF和Grz B的表达水平,比较各组差异。结果与正常对照组相比,普通型组和重型组EV71手足口病患儿急性期两种细胞中PRF和Grz B的表达水平均升高,差异有统计学意义(均P 0. 05)。普通型组和重型组EV71手足口病恢复期患儿CD8~+T细胞PRF、Grz B的表达水平较急性期明显下降,但仍高于正常对照组(均P 0. 05)。NK细胞PRF、Grz B的表达水平:普通型组和重型组急性期比较,差异均无统计学意义(均P 0. 05);普通型组EV71手足口病恢复期患儿较急性期虽稍升高,但差异仍无统计学意义(均P 0. 05);重型组EV71手足口病恢复期患儿较急性期明显升高(均P 0. 05)。结论 CD8~+T、NK细胞PRF和Crz B在EV71手足口病发病中起着一定作用。     

Plasmid-mediated doxycycline resistance in a Yersinia pestis strain isolated from a rat

The emergence of antibiotic-resistant Yersinia pestis strains represents a public health concern. Two antibiotic-resistant Y. pestis strains isolated from Madagascar have been previously identified and characterised. Both strains carried conjugative plasmids that conferred resistance to streptomycin or to multiple antibacterial drugs, respectively. Here we characterised a novel Y. pestis strain (IP2180H) that exhibited resistance to doxycycline. This strain was isolated from a rat in Antananarivo (Madagascar) in 1998. Resistance was carried by a conjugative plasmid (pIP2180H) homologous to pB71 from Salmonella enterica. The plasmid of the previously identified streptomycin-resistant Y. pestis strain was also sequenced and it was found that the three antibiotic resistance Y. pestis plasmids sequenced until now are genetically unrelated and are also unrelated to multidrug resistance plasmids from the phylogenetically close bacterial species Yersinia pseudotuberculosis. The fact that the three antibiotic-resistant Malagasy Y. pestis strains were isolated from different hosts, at different times, from distant locations, and carried unrelated plasmids indicates independent horizontal acquisition of genetic material and further demonstrates the capacity of Y. pestis to acquire antibiotic resistance plasmids under natural conditions. Since these resistance plasmids can frequently carry or easily trap antibiotic resistance cassettes, the emergence of new multidrug-resistant Y. pestis strains may be expected and would represent a major health threat.     

Association between X-ray repair cross-complementing group 1 Arg399Gln polymorphism and male infertility: An update meta-analysis

Numerous studies concentrate on the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphism and male infertility; however, the results remain inconclusive and inconsistent. Hence, this meta-analysis was conducted to get a precise estimation of the correlation. PubMed, Web of Science, Embase, Scopus and China National Knowledge Infrastructure (CNKI) databases were searched to identify the all relevant studies before 3 May 2020. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of the association. Finally, six studies with 1,886 cases and 1,212 controls were included in our study. The result indicated that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility under allelic model (A-allele vs. G-allele: OR = 1.183, p = .003), heterozygote genetic model (AA vs. GA: OR = 1.256, p = .027), recessive genetic model (AA vs. GG + GA: OR = 1.279, p = .012) and dominant genetic model (AA + GA vs. GG: OR = 1.218, p = .026). In addition, in Asian subgroup, statistic correlation remained significant in allelic model (A-allele vs. G-allele: OR = 1.145, p = .025) with rare heterogeneity (I² = 0%). In summary, our meta-analysis suggested that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility and the A-allele might be a risk factor for this disease, especially in Asians.     

Glutaminase1 heterozygous mice show enhanced trace fear conditioning and Arc/Arg3.1 expression in hippocampus and cingulate cortex

Mice heterozygous for a mutation in the glutaminase (GLS1) gene (GLS1 HZ mice), with reduced glutamate recycling and release, display reduced hippocampal function as well as memory of contextual cues in a delay fear conditioning (FC) paradigm. Here, we asked whether this deficit reflects an inability to process contextual information or a selective alteration in salience attribution. In addition, we asked whether baseline and activity-induced hippocampal activity were diminished in GLS1 HZ mice. For this purpose, we manipulated the relative salience of the conditioned stimulus (CS) and contextual cues in FC tasks, and examined gene expression of the immediate early gene Arc (Arc/Arg3.1) in hippocampus and anterior cingulate cortex (ACC) following trace FC (tFC). The results indicate that GLS1 HZ mice succeed in processing contextual information when the salient CS is absent or less predictive. In addition, in the hippocampus-dependent tFC paradigm GLS1 HZ mice display enhanced CS learning. Furthermore, while baseline arc activation was reduced in GLS1 HZ mice in the hippocampus, in line with previous fMRI findings, it was enhanced in the hippocampus and anterior cingulate cortex following tFC. These findings suggest that GLS1 HZ mice have a pro-cognitive profile in the tFC paradigm, and this phenotype involves activation of both hippocampus and ACC.Taken together with previous work on the GLS1 HZ mouse, this study sheds light on the importance of glutamate transmission to memory processes that require the allocation of attentional resources, and extends our understanding of the underpinnings of attention deficits in SZ.     

Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.     

山东省首例手足口病死亡病例调查与确认报告

手足口病是5岁以下幼儿的常见病,一般预后较好,但如果救治不及时易发展为重症,甚至死亡。2014年7月1日,菏泽市报告了一例手足口病死亡病例,该病例亦为山东省首例死亡病例。为了确认该病例的感染病原体和死亡原因,通过流行病学调查方法、询问患者家属及医务人员、查阅病例等方法了解到该病例先后在两家村级卫生室就诊,后转到市传染病医院,虽经极力抢救,仍因手足口病合并病毒性脑炎和神经源性肺水肿,呼吸、循环衰竭而死。经肛拭子标本实时定量PCR检测,该病例检测结果为EV71感染。应进一步加强手足口病的防控措施,重点关注对农村地区的病例指导时就医,降低手足口病的重症率和死亡率。