An inactivated recombinant rabies CVS-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice

The rabies virus (RABV) G protein is the primary contributor to the pathogenicity and protective immunity of RABV. In this study, we generated a recombinant rCVS-11-G strain containing two copies of the G protein derived from the pathogenic wild-type (wt) CVS-11 strain and based on its infectious clone. Compared with the wtCVS-11 strain, the rCVS-11-G strain possessed a larger virion and 1.4-fold more G protein, but it exhibited a similar growth property to the rCVS-11 strain, including passaging stability in vitro. qPCR results showed that the two G genes were over-expressed in BHK-21 cells infected with the rCVS-11-G strain. However, the rCVS-11-G strain presented an 80 % lower LD₅₀ than the wtCVS-11 strain when intracranially (i.c.) inoculated in adult mice. Adult mice that were either intracranially (i.c.) or intramuscularly (i.m.) inoculated with rCVS-11-G strain developed more acute neurological symptoms and greater mortality than those inoculated with the wtCVS-11 strain. Furthermore, the rCVS-11-G strain was more easily and rapidly taken up by neuroblastoma cells. These data indicated that the rCVS-11-G strain might have increased neurotropism because of the over-expression of the pathogenic G protein. The inactivated rCVS-11-G strain induced significantly higher levels of virus neutralization antibodies and provided better protection from street rabies virus challenge in mice. Therefore, the rCVS-11-G strain may be a promising inactivated vaccine strain due to its better immunogenicity.     

Rare copy number variation in cerebral palsy

Recent studies have established the role of rare copy number variants (CNVs) in several neurological disorders but the contribution of rare CNVs to cerebral palsy (CP) is not known. Fifty Caucasian families having children with CP were studied using two microarray designs. Potentially pathogenic, rare (<1% population frequency) CNVs were identified, and their frequency determined, by comparing the CNVs found in cases with 8329 adult controls with no known neurological disorders. Ten of the 50 cases (20%) had rare CNVs of potential relevance to CP; there were a total of 14 CNVs, which were observed in <0.1% (<8/8329) of the control population. Eight inherited from an unaffected mother: a 751-kb deletion including FSCB, a 1.5-Mb duplication of 7q21.13, a 534-kb duplication of 15q11.2, a 446-kb duplication including CTNND2, a 219-kb duplication including MCPH1, a 169-kb duplication of 22q13.33, a 64-kb duplication of MC2R, and a 135-bp exonic deletion of SLC06A1. Three inherited from an unaffected father: a 386-kb deletion of 12p12.2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25.3, and a 265-kb duplication of DAAM1. This is the first systematic study of CNVs in CP, and although it did not identify de novo mutations, has shown inherited, rare CNVs involving potentially pathogenic genes and pathways requiring further investigation.     

经颅磁刺激联合ESDM对孤独症患儿的疗效分析*

目的 探讨经颅磁刺激联合早期介入丹佛康复训练模式（ESDM）对孤独症患儿的治疗效果。方法 采用巢式病例对照研究法,以确诊孤独症为研究起点,以治疗6个月为研究终点,选取2016年1月—2018年6月徐州市儿童医院确诊并治疗的孤独症患儿患者92例作为研究对象。分为常规康复组（常规康复训练治疗）和颅磁丹佛组（经颅磁刺激联合ESDM治疗）,每组46例。对比分析常规康复组和颅磁丹佛组的韦氏儿童认知功能（WISC）评分、儿童孤独症症状（CARS）评分、孤独症行为（ABC）评分及临床疗效的差异。结果 治疗后常规康复组和颅磁丹佛组的WISC和ABC评分较治疗前提高（P?<0.05）,颅磁丹佛组升幅更大（P?<0.05）;治疗后常规康复组和颅磁丹佛组的CARS评分较治疗前降低（P?<0.05）,颅磁丹佛组降幅更大（P?<0.05）;颅磁丹佛组治疗有效率（84.78%）优于常规康复组（65.22%）（P?<0.05）。结论 经颅磁刺激联合ESDM能更有效地改善孤独症症状,在小儿孤独症治疗中的临床价值确切。     

Effect of low intensity pulsed ultrasound on repairing the periodontal bone of Beagle canines

Objective:To investigate the repairing effect of low intensity pulsed ultrasound(LIPUS)on the Beagle canines periodontal bone defect.Methods:A total of 12 Beagle dogs with periodontal bone defect model were randomly divided into control group,LIPUS group,guided tissue regeneration(GTR)group and LIPUS+GTR group,with three in each.After completion of the models,no other proceeding was performed in control group;LIPUS group adopt direct exposure to radiation line LIPUS processing 1 week after modeling;GTR group adopted treatment with GTR,following the CTR standard operation reference;LIPUS+GTR group was treated with LIPUS joint GTR.Temperature change before treatment and histopathological change of periodontal tissue after repair was observed.Results:There was no significant difference in temperature changes of periodontal tissue between groups(P0.05).The amount and maturity of LIPUS+GTR group were superior to other groups;new cementum,dental periodontal bones of GTR group were superior to the control group but less than LIPUS group;new collagen and maturity of the control group is not high relatively.Conclusions:LIPUS can accelerate the calcium salt deposition and new bone maturation,thus it can serve as promoting periodontal tissue repair,and shortening the periodontal tissue repair time.     

蟾毒灵对人肝癌细胞增殖与侵袭的影响

目的:研究蟾毒灵(bufalin,Bu)对肝癌BEL-7402细胞生长、迁移侵袭的作用.方法:体外培养人肝癌BEL-7402细胞,应用CCK-8比色法、流式细胞仪、Transwell小室迁移侵袭实验观测不同浓度和作用时间Bu对肝癌细胞增殖、迁移、侵袭的影响.结果:Bu明显抑制肝癌BEL-7402细胞生长和增殖,呈浓度-时间效应关系;0.085μg/mL Bu分别作用于肝癌BEL-7402细胞48、72 h,肝癌细胞周期阻滞于G2/S期[48 h(G2:t=-6.618,P<0.01;S:t=-5.339,P<0.01),72 h(G2:t=-14.273,P<0.01;S:t=-4.812,P<0.01)];0.085μg/mL Bu作用肝癌BEL-7402细胞72 h,显著抑制肝癌细胞迁移(t=11.717,P<0.01)和侵袭(t=5.437,P<0.01).结论:Bu能抑制肝癌细胞迁移、侵袭,并且通过阻滞肝癌细胞周期于G2/S期,抑制肝癌细胞增殖,其生长抑制作用呈时间和剂量依赖效应.     

Association analysis of genes in serotonin pathway with attention and executive function in patients with bipolar affective disorder

Background

The reason why it is difficult to identify susceptibility genes attributed to bipolar disorder (BPD) is the phenotypic heterogeneity. The use of endophenotypes has been advocated as one possible strategy to discovery cause variants of BPD.

Methods

A total of 164 patients with BPD and 164 matched controls were employed in the present research. Fifty-two single nucleotide polymorphisms (SNPs) within the genes in serotonin pathway were selected for genotyping using the GoldenGate genotyping assay. All participants completed three neurocognitive tests including the tower of Hanoi (TOH), the Wisconsin card sorting test (WCST) and Trail making tests (TMTA and TMTB-M).

Results

Patients with BPD demonstrated a wide range of deficits in mental activities of attention and speed of information processing, and executive function. Significant interactions between rs2760347 in 5HTR2A gene and diagnosis were found for the executive time of TOH, with β = 11.82 and P = 0.002 (adjusted P = 0.03 after Bonferroni correction).

Conclusions

Cognitive impairments existing in BPD may be particularly notable in certain domains of attention and executive function, and 5HTR2A gene may be involved in modulating executive function of BP-I patients.     

Clinical progress and risk factors for death in severe Fever with thrombocytopenia syndrome patients

Background.?Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate of 12%. The clinical factors for death in SFTS patients remain unclear. Methods.?Clinical features and laboratory parameters were dynamically collected for 11 fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to evaluate the risk factors associated with death. Results.?Dynamic tracking of laboratory parameters revealed that during the initial fever stage, the viral load was comparable for the patients who survived as well as the ones that died. Then in the second stage when multi-organ dysfunction occurred, from 7-13 days after disease onset, the viral load decreased in survivors but it remained high in the patients that died. The key risk factors that contributed to patient death were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase fraction, as well as the appearance of CNS (central nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular coagulation, and multi-organ failure. All clinical markers reverted to normal in the convalescent stage for SFTS patients who survived. Conclusions.?We identified a period of 7-13 days after the onset of illness as the critical stage in SFTS progression. A sustained serum viral load may indicate that disease conditions will worsen and lead to death.