Application of graph neural network and feature information enhancement in relation inference of sparse knowledge graph

At present,knowledge embedding methods are widely used in the field of knowledge graph(KG)reasoning,and have been successfully applied to those with large entities and relationships.However,in research and production environments,there are a large number of KGs with a small number of entities and relations,which are called sparse KGs.Limited by the performance of knowledge extraction methods or some other reasons(some common-sense information does not appear in the natural corpus),the relation between entities is often incomplete.To solve this problem,a method of the graph neural network and information enhancement is proposed.The improved method increases the mean reciprocal rank(MRR)and Hit@3 by 1.6%and 1.7%,respectively,when the sparsity of the FB15K-237 dataset is 10%.When the sparsity is 50%,the evaluation indexes MRR and Hit@10 are increased by 0.8%and 1.8%,respectively.

Molecular Epidemiological Analysis of Echovirus 19 Isolated From an Outbreak Associated With Hand, Foot, and Mouth Disease (HFMD) in Shandong Province of China

To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 （El9） isolates collected from an outbreak associated with hand, foot and mouth disease （HFMD） in Tai＇an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid （VP1） genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions （5′-UTR）. Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.

Elevated Plasma Tissue-type Plasminogen Activator (t-PA) and Soluble Throm-bomodulin in Patients Suffering From Severe Acute Respiratory Syndrome (SARS) as a Possible Index for Prognosis and Treatment Strategy

To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.

Regulatory effects of the combination of berberine and ginsenoside Rb1 on high-fat diet-induced nonalcoholic fatty liver disease via AMPK pathway and improved pharmacokinetics

目的：评价小檗碱（BBR）联合人参皂苷Rb1（G-Rb1）对高脂饮食（HFD）诱导的大鼠非酒精性脂肪肝病（NAFLD）的保护作用并阐明其作用机制.方法：大鼠给予高脂饮食6周,然后分别给予BBR（50mg/kg）,G-Rb1（100mg/kg）,BBR（50mg/kg）＋G-Rb1（100mg/kg）和非诺贝特（40mg/kg）治疗.通过组织学检查染色评估肝组织.在人肝癌细胞HepG2细胞系中,通过蛋白质印迹检测AMP-活化蛋白激酶（AMPK）和乙酰辅酶A羧化酶（ACC）蛋白的表达,定量PCR检测肉毒碱棕榈酰转移酶1和3-羟基-3-甲基戊二酰辅酶A还原酶mRNA的水平.药代动力学评估包括体内BBR和G-Rb1的生物利用度,以及体外肠道细菌的G-Rb1代谢.结果：根据肝脏甘油三酯含量分析和肝脏切片组织学评价,与单用组相比,BBR联合G-Rb1可显著改善HFD诱导的肥胖大鼠的肝脏脂肪堆积.在用BBR和G-Rb1处理的肝癌细胞HepG2中,肝脏AMPK的活化和ACC的磷酸化显着升高.与AMPK的活化一致,肉毒碱棕榈酰转移酶1的mRNA表达被刺激,而3-羟基-3-甲基戊二酰辅酶A还原酶的转录被抑制.药代动力学分析显示BBR增加了SD大鼠G-Rb1的生物利用度.此外,BBR在体外防止粪便溶液中G-Rb1的降解.结论：BBR联合G-Rb1通过作用于AMPK信号通路改善NAFLD,BBR可通过促进G-Rb1在肠道吸收来增强G-Rb1生物利用度,小檗碱联用人参皂苷Rb1可能是治疗NAFLD的有效药物.

Genetic Characterization of Fusion Protein of Human Respiratory Syncytial Virus: Beijing

Objective Fusion protein is a subunit of the human respiratory syncytial virus(HRSV)and a potential vaccine candidate.Thus,a study on the genetic characteristics of F protein was considered important for further investigations in this field.The aim of this study was to determine the prevalence and genetic diversity of the F gene of HRSV infections in hospitalized pediatric patients in Beijing with acute lower respiratory tract infections and to compare the circulating genotypes that are currently found worldwide.Methods HRSV particles were amplified by RT-PCR and the PCR products were purified for sequencing.Further analysis was carried out by Bioedit and MEGA 3.0 biological software programs.Results Seventy-six samples(23.1%)were positive for HRSV.The percentage of cases in patients younger than 1year was 84.21%.Among the six Beijing isolates,four belonged to subgroup A,whose respective F genes shared97.0%-97.4%nucleotide sequence identity and 92.1%-93.0%amino acid sequence identity.The other two isolates belonged to subgroup B.Here,97.3%and 98.2%sequence identity were found at nucleotide and amino acid levels,respectively.Conclusions Phylogenetic analysis of nucleotide sequences revealed that those four isolates within subgroup A were monophyletic and closely related to each other,but those two within subgroup B distributed in two distinct clusters.Subgroup A and B strains co-circulated,indicating that two different transmission chains occurred in Beijing from 2003-2004.

Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition)

Background Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treat-ments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. Methods National Health Commission of China assembled an expert committee for a revision of the guidelines. The com-mittee included 33 members who are specialized in diagnosis and treatment of HFMD. Results Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia;(2) involvement of nervous system;(3) worsening respiratory rate and rhythm;(4) circulatory dysfunction;(5) elevated peripheral WBC count;(6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. Conclusion The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

HIV prevalence in suspected Ebola cases during the 2014-2016 Ebola epidemic in Sierra Leone

Background:The 2014-2016 Ebola virus epidemic in West Africa was the largest outbreak of Ebola virus disease(EVD)in history.Clarifying the influence of other prevalent diseases such as human immunodeficiency virus infection and acquired immune deficiency syndrome(HIV/AIDS)will help improve treatment and supportive care of patients with EVD.Case presentation:We examined HIV and hepatitis C virus(HCV)antibody prevalence among suspected EVD cases from the Sierra Leone-China Friendship Biological Safety Laboratory during the epidemic in Sierra Leone.HIV and HCV antibodies were tested in 678 EVD-negative samples by enzyme-linked immunosorbent assay.A high HIV prevalence(17.6%)and low HCV prevalence(0.22%)were observed among the suspected cases.Notably,we found decreased HIV positive rates among the suspected cases over the course of the epidemic.This suggests a potentially beneficial effect of an improved public health system after assistance from the World Health Organization and other international aid organizations.Conclusions:This EVD epidemic had a considerable impact on the public health system and influenced the prevalence of HIV found among suspected cases in Sierra Leone,but also provided an opportunity to establish a better surveillance network for infectious diseases.

Glycopeptide ligation via direct aminolysis of selenoester

Direct aminolysis of selenoester in aqueous media was investigated as a glycopeptide ligation strategy.This strategy allows the peptide and glycopeptide ligation to proceed smoothly(even with hindered amino acids) without the need of cysteine residue, N-terminal thiol auxiliary or coupling additive, and to afford the corresponding amide products in excellent yields. No epimerization was observed during ligation reations. In this work, the selenoester of unprotected glycopeptide was readily prepared, and the direct aminolysis of glycopeptide selenoester was successfully applied to synthesize MUC1 mucin sequence efficiently.