Background Aseptic meningitis is most often caused by enteroviruses (EVs), but EVs associated with aseptic meningitis have not yet been reported in Liaocheng. The aim of this study was to determine the prevalence and genetic characteristics of EVs causing aseptic meningitis in children in Liaocheng. Methods We reviewed the epidemiological and clinical characteristics of 504 paediatric cases of aseptic meningitis in Liaocheng from 2018 to 2019 and analysed the phylogeny of the predominant EV types causing this disease. Results A total of 107 children were positive for EV in cerebrospinal fluid samples by nested PCR. Most of the positive patients were children 13 years old or younger and had symptoms such as fever, headache and vomiting (P < 0.05). The seasons with the highest prevalence of EV-positive cases were summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year study period. Phylogenetic analyses demonstrated that the E18 and E6 isolates belonged to subgenotype C2, while the E11 isolates belonged to subgenotype D5. VP1 analysis suggested that only one lineage of these three types was cocirculating in the Liaocheng region. Conclusions This study demonstrated the diverse EV genotypes contributing to a large outbreak of aseptic meningitis in Liaocheng. Therefore, large-scale surveillance is required to assess the epidemiology of EVs associated with aseptic meningitis and is important for the diagnosis and treatment of aseptic meningitis in Liaocheng.

Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in non-pregnant state. However, in addition to reproductive tissues, reproductive cycle could also perform global regulation because the receptors of two major female hormones fluctuating throughout the cycle, estrogen and progesterone, are widely distributed. Therefore, a multi-tissue gene expression landscape is in continuous demand for better understanding the systemic changes during the reproductive cycle but remains largely undefined. Here we delineated a transcriptomic landscape covering 15 tissues of C57BL/6J female mice in two phases of estrous cycle, estrus and diestrus, by RNA-sequencing. Then, a number of genes, pathways, and transcription factors involved in the estrous cycle were revealed. We found the estrous cycle could widely regulate the neuro-functions, immuno-functions, blood coagulation and so on. And behind the transcriptomic alteration between estrus and diestrus, 13 transcription factors may play important roles. Next, bioinformatics modeling with 1,263 manually curated gene signatures of various physiological and pathophysiological states systematically characterized the beneficial/deleterious effects brought by estrus/diestrus on individual tissues. We revealed that the estrous cycle has a significant effect on cardiovascular system (aorta, heart, vein), in which the anti-hypertensive pattern in aorta induced by estrus is one of the most striking findings. Inspired by this point, we validated that two hypotensive drugs, felodipine and acebutolol, could exhibit significantly enhanced efficacy in estrus than diestrus by mouse and rat experiments. Together, this study provides a valuable data resource for investigating reproductive cycle from a transcriptomic perspective, and presents models and clues for investigating precision medicine associated with reproductive cycle.

Jiedu Huoxue Decoction (JHD), a recommended traditional prescription for patients with severe COVID-19, has appeared in the treatment protocols in China. Based on bioinformatics and computational chemistry methods, including molecular docking, molecular dynamics (MD) simulation, and Molecular Mechanics Generalized Born Surface Area (MM/GBSA) calculation, we aimed to reveal the mechanism of JHD in treating severe COVID-19. The compounds in JHD were obtained and screened on TCMSP, SwissADME, and ADMETLab platforms. The compound targets were obtained from TCMSP and STITCH, while COVID-19 targets were obtained from Genecards and NCBI. The protein-protein interaction network was constructed by using STRING. Gene Ontology (GO) and KEGG enrichment were performed with ClueGO and R language. AutoDock vina was employed for molecular docking. 100 ns MD simulation of the optimal docking complex was carried out with AmberTools 20. A total of 84 compounds and 29 potential targets of JHD for COVID-19 were collected. The key phytochemicals included quercetin, luteolin, β-sitosterol, puerarin, stigmasterol, kaempferol, and wogonin, which could regulate the immune system. The hub genes included IL6, IL10, VEGFA, IL1B, CCL2, HMOX1, DPP4, and ACE2. ACE2 and DPP4 were related to SARS-CoV-2 entering cells. GO and KEGG analysis showed that JHD could intervene in cytokine storm and endothelial proliferation and migration related to thrombosis. The molecular docking, 100 ns MD simulation, and MM/GBSA calculation confirmed that targets enriched in the COVID-19 pathway had high affinities with related compounds, and the conformations of the puerarin-ACE2, quercetin-EGFR, luteolin-EGFR, and quercetin-IL1B complexes were stable. In a word, JHD could treat COVID-19 by intervening in cytokine storm, thrombosis, and the entry of SARS-CoV-2, while regulating the immune system. These mechanisms were consistent with JHD's therapeutic concept of “detoxification” and “promoting blood circulation and removing blood stasis” in treating COVID-19. The research provides a theoretical basis for the development and application of JHD.

Background: Aseptic meningitis is the most common viral infection caused by human enteroviruses, but enteroviruses associated with aseptic meningitis in Liaocheng have not been reported yet. The aim of this study was to determine prevalence and genetic characteristics of enteroviruses causing aseptic meningitis in children in Liaocheng. Methods: We reviewed the epidemiological and clinical characteristics of 504 pediatric cases with aseptic meningitis in Liaocheng from 2018 to 2019, and analyzed the phylogeny of the predominant enterovirus (EV) types causing this disease. Results: A total of 107 children were positive for EV by the nested-PCR in cerebrospinal fluid samples. Most of the positive patients were children within 13 years old, had symptoms such as fever, headache and vomiting (P<0.05). The most prevalent seasons of EV-positive cases accurred in summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year period. Phylogentic analyses demonstrated that E18 and E6 isolates belonged to subgenotype C2, while E11 isolates belonged to subgenotype D5. The VP1 analysis suggested that only one lineage of these three types were co-circulating in Liaocheng region. Conclusions: This study demonstrated the diversified enterovirus genotypes attributing to the large outbreak of aseptic meningitis in Liaocheng. Therefore, the large-scale surveillance is required to the epidemiology of enteroviruses associated with aseptic meningitis, and is important for diagnosis and treatment of aseptic meningitis in Liaocheng.