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    Current Advance of Basic and Clinical Medical Virology
    Research progress on factors influencing the protective effects of influenza vaccines
    Yuelong SHU,Simin WEN
    Journal of Shandong University (Health Sciences). 2021, 59(5):  1-7.  doi:10.6040/j.issn.1671-7554.0.2021.0319
    Abstract ( 1063 )   HTML ( 33 )   PDF (1140KB) ( 625 )   Save
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    Annual vaccination is the best prevention of influenza. However, the protective effects of influenza vaccines currently used are poor due to variation of influenza viruses. The protective effects can also be affected by other factors including the genetic factor, and it is important to fully identify these related factors. In this paper, we briefly summarized the factors that may influence the protective effects of influenza vaccines from the aspects of the matching degree of circulating strains and vaccine strains, vaccine factors and host factors, and proposed the development direction of new influenza vaccines in the future.

    Current status and prospect of viral vaccines research and development
    Kai WANG
    Journal of Shandong University (Health Sciences). 2021, 59(5):  8-14.  doi:10.6040/j.issn.1671-7554.0.2021.0273
    Abstract ( 2825 )   HTML ( 167 )   PDF (1285KB) ( 1152 )   Save
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    Virus infection can cause several diseases in human. In the past decades, outbreaks and epidemics of respiratory infectious diseases caused by coronary viruses, especially coronavirus disease 2019 (COVID-19), have become serious health hazards and posed huge challenges to public health. The development and application of viral vaccines have been an important means to counteract the spread of viruses. Historically, poliovirus and hepatitis B virus vaccines have successfully suppressed the transmission of diseases and provided a model for the development of vaccines. Recently, the emergence of novel technologies and platforms such as recombinant viral vector and mRNA vaccine has provided new approaches to the development of vaccines against emerging infectious diseases including COVID-19. This paper reviews the current situation and progress of platforms, summarizes problems to be solved, and forecasts the directions of viral vaccines development.

    SARS-CoV-2 infection, innate immunity and inflammatory response
    Xi ZHOU,Muhan HUANG,Yujie REN,Yang QIU
    Journal of Shandong University (Health Sciences). 2021, 59(5):  15-21.  doi:10.6040/j.issn.1671-7554.0.2021.0368
    Abstract ( 3109 )   HTML ( 188 )   PDF (1512KB) ( 912 )   Save
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    Coronavirus disease 2019 (COVID-19), which is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become the worst pandemic and public health crisis across the globe once a century. This pandemic has caused huge losses in both human lives and global economy. Innate immunity is the first line of defense against pathogenic invasions. Extensive studies by scientists in China and the world have reported that SARS-CoV-2 can employ multiple strategies to evade host innate immunity, and such immune evasion mechanisms have become critical contributing factors for the pathogenicity of SARS-CoV-2. On the other hand, the pathogenesis of COVID-19 has been found to be closely relevant with the pro-inflammatory responses induced by SARS-CoV-2 infection in humans. This paper provides a brief review to the relationship between SARS-CoV-2 infection and innate immunity as well as inflammation.

    Zika virus infection and disease
    Jing AN,Zhengran SONG,Zida ZHEN,Yanhua WU
    Journal of Shandong University (Health Sciences). 2021, 59(5):  22-29.  doi:10.6040/j.issn.1671-7554.0.2021.0332
    Abstract ( 1318 )   HTML ( 29 )   PDF (1868KB) ( 263 )   Save
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    Zika virus (ZIKV) is an arthropod-borne virus in the family Flaviviridae, which is the pathogen of ZIKV disease (ZVD). First identified in 1947, ZIKV caused sporadic infections in human. However, since 2007, ZIKV infections have spread around the world and caused severe neurological complications such as microcephaly and Guillain-Barré syndrome (GBS). Notably, ZIKV can be sexually transmitted and affect male reproductive health. The World Health Organization declared in February 2016 ZIKV to be an international public health emergency. This paper provides a brief review to ZIKV epidemiology and ZVD complications.

    Impact of EBV on the epigenetics of gastric carcinoma
    Bing LUO
    Journal of Shandong University (Health Sciences). 2021, 59(5):  30-39.  doi:10.6040/j.issn.1671-7554.0.2021.0272
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    Epstein-Barr virus (EBV), an important human tumor virus, is closely related to the occurrence of a variety of tumors, including 10% gastric cancer. The role of EBV in gastric carcinogenesis has received increasing attention and EBV is considered to be another pathogenic factor in addition to Helicobacter pylori. In EBV-associated gastric carcinoma (EBVaGC), a typical characteristic is the extensive methylation of viral and host genomes, which expresses a limited number of viral genes including EBV nuclear antigen 1, EBV encoded small RNAs, Bam HI-A rightward transcripts, latent membrane protein 2A and miRNAs. Combined with other epigenetic mechanisms, EBV infection acts as an epigenetic driver of EBVaGC oncogenesis. This review will discuss the impact of EBV on the epigenetic alterations in EBVaGC and its role in oncogenesis.

    Prevention and control of emerging viral infectious diseases and biosafety
    Hongling WEN,Xiaoying XU
    Journal of Shandong University (Health Sciences). 2021, 59(5):  40-45.  doi:10.6040/j.issn.1671-7554.0.2021.0308
    Abstract ( 2051 )   HTML ( 74 )   PDF (1430KB) ( 757 )   Save
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    In recent years, the frequent occurrences of emerging infectious diseases, especially the interspecies transmission of animal-borne viruses, have brought immense challenges to the prevention and control of infectious diseases and biosafety, such as laboratory biosafety, frontier port biosafety and dual-use biotechnology. Currently the international biosafety situation is serious, characterized with internationalization, extreme harm and complicated development. Biosafety has become a major issue endangering national security, which has aroused great concern about virology and biological threats. In this paper, the occurrence, prevention and control of emerging viral infectious diseases and the status quo of biosafety in basic research were reviewed, various problems were summarized, and the future development of biosafety was prospected.

    Current progress on prevention of mother to child transmission of hepatitis B virus
    Yuchen FAN
    Journal of Shandong University (Health Sciences). 2021, 59(5):  46-51,67.  doi:10.6040/j.issn.1671-7554.0.2021.0262
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    Hepatitis B virus (HBV) infection is a global public threat, which leads to chronic hepatitis B (CHB), liver cirrhosis, liver cancer and liver failure. Mother to child transmission is one of the main ways of HBV transmission. It is of great significance to block the mother to child transmission of HBV through effective intervention to reduce the infection rate of HBV and reduce the burden of HBV related diseases. With the continuous development of China's economy and medical level, measures to prevent mother to child transmission of HBV are constantly improved, which greatly reduces the prevalence of HBV in China. This article summarizes the clinical guidelines and norms for the prevention of mother to child transmission of HBV in China, and summarizes the hot issues and related progress in this field.

    Genetic characteristics of H10 subtype avian influenza virus in three southern provinces of China
    Xiaoxu ZENG,Heng ZHANG,Ming JIAO,Tao CHEN,Xiyan LI,Weijuan HUANG,Jing YANG,Dayan WANG
    Journal of Shandong University (Health Sciences). 2021, 59(5):  52-59.  doi:10.6040/j.issn.1671-7554.0.2021.0220
    Abstract ( 1068 )   HTML ( 5 )   PDF (9707KB) ( 242 )   Save
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    Objective: To explore the genetic characteristics of avian influenza virus (AIVs) between 2014 and 2019 in three southern provinces of China. Methods: A total of 30 231 environment samples isolated from Jiangxi, Hunan and Guangxi provinces from 2014 to 2019 were tested for flu A with real-time RT-PCR. If the testing results were positive, the samples were propagated in SPF chicken embryonated eggs. All positive AIVs isolations were sequenced. CLC, CD-HIT, MAFFT v7.037 and MEGA v6.06 software were used to analyze the influenza sequences. Results: Altogether 11 H10 subtype AIVs were isolated. Whole genome sequencing and phylogenetic analysis revealed that all genes were classified into Eurasian lineage, except 3 N8 genes in the North American lineage. JX24472 had close relationship with human infection H10N8 AIVs in its HA segment. The internal genome of 5 H10N3 subtype AIVs isolated from Jiangxi Province suggested their genome were diverse and complex. Molecular characteristic analysis of H10 subtype AIVs revealed that several mutations in key amino acid sites were associated with receptor binding sites, pathogenicity in mice and transmissibility in mammals. Conclusion: Phylogenetic analyses of the 11 H10 subtype AIVs isolated in this research suggested that they were in different clade with human infected H10N8 AIVs, except JX24472. Whereas the amino acid characterization analysis suggested that these H10 subtype viruses had the potential to infect human or poultry to make them sick. Therefore, it is necessary to strengthen the continuous surveillance of H10 subtype AIVs and prepare for the next potential pandemic.

    Positive distribution of four dominant enteroviruses associated with hand, foot and mouth disease and VP1 genotypes in Jinan, China, 2012-2017
    Hengyun GUAN,Chunrong WANG,Lanzheng LIU,Huailong ZHAO,Aiying BAI,Huiyu JIANG,Hua DONG,Na LI,Xiaoying SHAN,Hongqi CHENG
    Journal of Shandong University (Health Sciences). 2021, 59(5):  60-67.  doi:10.6040/j.issn.1671-7554.0.2021.0278
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    Objective: To elucidate the dominant enteroviruses associated with hand, foot and mouth disease (HFMD) and the distributions of VP1 genotypes in Jinan City. Methods: Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), coxsackievirus A6 (CV-A6) and coxsackievirus A10 (CV-A10) in 4929 HFMD specimens from 2012 to 2017 in Jinan. According to different years, 65 virus isolates of HFMD were retrospectively collected, including 17 strains of EV-A71, 16 of CV-A16, 20 of CV-A6 and 12 of CV-A10. The VP1 gene of enteroviruses was amplified by RT-PCR and the nucleotide sequencing was performed. Nucleotide homology analyses were performed and phylogenetic trees were constructed on the VP1 gene. Results: The dominant enteroviruses of HFMD were CV-A16 (28.3%), EV-A71(27.3%), CV-A6(17.0%) and CV-A10(3.0%) in Jinan. The lengths of VP1 gene on CV-A16, EV-A71, CV-A6 and CV-A10 amplified by RT-PCR were 891 bp, 1 015 bp, 1 110 bp and 993 bp, respectively. The nucleotide homology was 93.0%-98.1% for EV-A71 strains, 87.4%-100.0% for CV-A16 strains, 87.6%-99.7% for CV-A6 strains, and 95.8%-99.4% for CV-A10 strains. The phylogenetic trees showed that EV-A71 strains belonged to C4a genotype in Jinan, CV-A16 strains had two genetic subtypes (B1b and B1a); CV-A6 strains located in clusters C, E and F, and CV-A10 strains located in cluster E. Conclusion: The dominant enteroviruses of HFMD are CV-A16, EV-A71, CV-A6 and CV-A10 from 2012 to 2017 in Jinan. The long-term dynamic monitoring of the distribution of VP1 genotypes is of great public health significance for improving the early warning sensitivity for HFMD.

    Genetic characteristics and molecular variation of human rhinovirus genetype B83 in Jinan
    Huailong ZHAO,Yan LYU,Hong ZHAO,Baotian ZHAO,Ying HAN,Jing PAN,Xiaoman DING,Chunrong WANG,Xiuyun HAN,Lanzheng LIU
    Journal of Shandong University (Health Sciences). 2021, 59(5):  68-72, 81.  doi:10.6040/j.issn.1671-7554.0.2021.0265
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    Objective: To analyze the genetic characteristics and molecular variation of human rhinovirus (HRV) identified in Jinan, 2020. Methods: The samples collected form influenza-like illness were tested by realtime RT-PCR and the HRV nucleic acid positive sample was sequenced with metagenome sequencing technology. Molecular variation and phylogenetic trees of VP4/VP2 coding region were analyzed using the softwares Lasergene 7.1 and MEGA 5.2. Results: The 7 219 nt complete genome sequence of JN909 was obtained. Phylogenetic analysis of VP4/VP2 coding region on HRV positive strain agreed with the serotype HRV B83. The JN909 was genetically closed to the SC0340 strain found in Seattle City of USA (GenBank accession number: MN306025), with a nucleotide similarity of 98.5% and deduced amino acid similarity of 99.7% of ORF, and there were 6 sites mutation between stains, in which substitutions A23T and P275L sites were located in VP1. Conclusion: There is a high homology between JN909 and SC0340 strains, and only 6 sites amino acid mutations occurs.

    Knockdowa of LncRNA H19 inhibits sympathetic nerve remodeling after myocardial infarction by regulating nerve growth factor
    ZHANG Xueli, ZHENG Lu, WANG Yu, WANG Kang, YAN Suhua
    Journal of Shandong University (Health Sciences). 2021, 59(5):  73-81.  doi:10.6040/j.issn.1671-7554.0.2020.1534
    Abstract ( 772 )   PDF (9043KB) ( 179 )   PDF(mobile) (8538KB) ( 4 )   Save
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    Objective To explore the roles of H19 and nerve growth factor(NGF)in the development of ventricular arrhythmias(VAs)after myocardial infarction(MI). Methods MI rat models were established by left coronary artery occlusion. (1)A total of 14 healthy Sprague Dawley(SD)rats were randomly divided into the MI group and sham group, with 7 rats in each group. Seven days after MI was induced, the rats were sacrificed to determine the H19 expression with qRT-PCR. (2)A total of 32 rats were randomly divided into 4 groups: sham+NC group, sham+siH19 group, MI+NC group and MI+siH19 group, with 8 rats in each group. H19-siRNA or the control virus was injected into the left ventricular myocardium of the rats. Programmed electrical stimulation was performed 7 days after MI was induced to observe the susceptibility to VAs. The effects of H19 on NGF, tyrosine hydroxylase(TH)and growth-associated protein 43(GAP43)were detected with qRT-PCR, Western blotting and immunofluorescence staining. (3)A total of 24 rats were randomly divided into the MI+NC group, MI+siH19 group and MI+siH19+LV-NGF group for rescue test, with 8 rats in each group. The expressions of NGF, TH and GAP43 were detected with Western blotting and immunofluorescence staining. Results The expression of H19 were up-regulated 7 days after MI was induced(P<0.001). H19 knockdown suppressed the positive staining area of TH and GAP43(P<0.001), decreased the susceptibility to VAs(P<0.01), and inhibited the expression of NGF(Z=-2.402, P=0.016). The inhibitory effect of H19 knockdown on sympathetic remodeling could be saved by overexpressed NGF(PTH<0.001, PGAP43=0.001). Conclusion H19 knockdown after myocardial infarction can inhibit sympathetic nerve remodeling by regulating the expressiou of NGF, thus reducing the incidence of arrhythmia.
    Effects of the intervention of Sonic Hedgehog signaling pathway on learning and memory ability in rats with intrauterine growth restriction
    LU You, QIE Di, WU Jinhui, YANG Fan
    Journal of Shandong University (Health Sciences). 2021, 59(5):  82-89.  doi:10.6040/j.issn.1671-7554.0.2021.0029
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    Objective To investigate the effects of the intervention of Sonic Hedgehog(Shh)signaling pathway on learning and memory ability in rats with intrauterine growth restriction(IUGR)and its possible mechanism. Methods The rat models of IUGR were established by feeding with low protein diet during pregnancy, and their newborn rats were divided into model group, Shh signaling pathway inhibitor cyclopamine group(CYC group)and Shh signaling pathway activator purmorphamine group(PUR group), 20 rats in each group. In addition, 20 normal newborn rats in the same period were selected as the normal control group. After intervention, Morris water maze test was performed to detect the learning and memory ability of newborn rats at the age of 30 days. Immunofluorescence BrdU/NeuN double labeling method was used to detect the proliferation level of hippocampal neurons. TUNEL staining was used to observe the level of cell apoptosis in hippocampus. Spectrophotometry was used to detect the activity of Caspase-3 in hippocampus. Western blotting was used to evaluate the expression levels of Shh signaling pathway related protein Smoothened(Smo), Gli-1 and Bcl-2 in hippocampus. Results Compared with the normal control group, the ability of learning and memory and the proliferation level of hippocampal neuron in the model group were decreased(P<0.05), the apoptosis level of hippocampus and the activity of Caspase-3 were increased(P=0.028, P=0.029), while the protein expression levels of Smo, Gli-1 and Bcl-2 were reduced in hippocampal tissue(P=0.017, P=0.026, P=0.031). Compared with the model group, the ability of learning and memory and the proliferation level of hippocampal neuron in the PUR group were increased(P<0.05), the apoptosis level of hippocampus and the activity of Caspase-3 were decreased(P=0.033, P=0.045), and the protein expression levels of Smo, Gli-1 and Bcl-2 in the hippocampus tissue were increased(P=0.041, P=0.016, P=0.033). However, compared with the model group, the above indicators of rats in the CYC group were worse, and the difference was statistically significant(P<0.05). Conclusion Activation of Shh signaling pathway can improve the learning and memory ability of IUGR newborn rats by promoting the proliferation of hippocampal neurons and inhibiting cell apoptosis.
    Early efficacy of double-column mobile bearing unicompartmental knee prosthesis in treating medial knee osteoarthritis
    MIAO Zhuang, LIU Peilai, LU Qunshan, YAO Tianxiao, LI Songlin, LUO Desu
    Journal of Shandong University (Health Sciences). 2021, 59(5):  90-95.  doi:10.6040/j.issn.1671-7554.0.2021.0142
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    Objective To investigate the early efficacy of double-column mobile bearing unicompartmental knee prosthesis in the treatment of medial knee osteoarthritis. Methods A prospective single-arm clinical trial was conducted and the clinical data of 30 patients with medial knee osteoarthritis treated with double-column mobile bearing unicompartmental knee prosthesis in our during 2018 and June. 2019 were collected. The functions, hematological indexes and imaging results were analyzed before surgery, and at day 7, 6 weeks, 3 and 6 months and 1 year after surgery. Results The functional scores of American Hospital for Special Surgery(HSS)were(68.03±10.34)before surgery and(90.52±4.57)1 year after surgery(P<0.05). The intraoperative blood loss was 135.50(127.97)mL. As of the last follow-up, no serious adverse events were reported including bearing dislocation, infection and prosthesis loosening. Conclusion The double-column mobile bearing unicompartmental knee prosthesis can substantially improve the knee joint functions in patients with knee osteoarthritis, and the performance of prosthesis is safe and reliable.
    Two cases of anti-Ma2 antibody positive encephalitis in children and literature review
    ZHAO Yongheng, GAO Liang, LI Baomin
    Journal of Shandong University (Health Sciences). 2021, 59(5):  96-103.  doi:10.6040/j.issn.1671-7554.0.2021.0120
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    Objective To screen the antibodies in 2 children with suspected autoimmune encephalitis, in order to explore the etiology, make a diagnosis, deepen the understanding of clinical manifestations, and guide the treatment. Methods Both children had clinical manifestations like general weakness with personality change, and convulsions with speech and motor disorders. Antibody screening was performed, and relevant literature was reviewed. Results Anti-Ma2 antibody serum antibodies were detected with Western blotting, and the patients were diagnosed as anti-Ma2 antibody positive encephalitis. The clinical features of 30 cases at home and abroad were compared and analyzed to deepen the understanding of the clinical manifestations. Conclusion Anti-Ma2 antibody positive encephalitis is caused by Anti-Ma2 antibody, and its clinical manifestations are varied. Antibody screening is beneficial to improve the diagnosis rate of this rare disease. Immunotherapy has good clinical efficacy.
    Mediating effects of locus of control on relationship between mindfulness and inner peace among medical students
    WANG Qing, ZHOU Miao, ZHAO Di, LI Ping
    Journal of Shandong University (Health Sciences). 2021, 59(5):  104-109.  doi:10.6040/j.issn.1671-7554.0.2020.1682
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    Objective To explore the mediating effects of locus of control between mindfulness level and inner peace of medical students. Methods A total of 455 medical students were assessed with Five Facet Mindfulness Questionnaire(FFMQ), Internality, Powerful Others and Chance Scale(IPC)and Inner Peace State Scale(IPSS). Data collected were analyzed with structural equation model. Results Mindfulness was moderately positively correlated with internal control(rs=0.367, P<0.01)and inner peace(rs=0.378, P<0.01), and low negatively correlated with opportunity(rs=-0.291, P<0.01)and influential others(rs=-0.182, P<0.01). Internal control was low positively correlated with inner peace(rs=0.327, P<0.01). Opportunity(rs=-0.210, P<0.01)and influential others(rs=-0.170, P<0.01)were low negatively correlated with inner peace. In addition, there was a mediating effect between mindfulness and inner peace of internal locus of control, accounting for 10.11%. The mediating effects of internal control and opportunity between description and inner peace were also valid, amounting for 43.50% and 16.04% respectively. Conclusion As mindfulness can affect the level of inner peace through the locus of control, targeted interventions based on mindfulness is significant to improve medical students’ level of inner peace.