Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo₂(OAc)₄ induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L^-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Circulating tumor DNA (ctDNA) comes from tumor, reflecting the genetic information of the tumor well, and will change with the progress of tumor. In recent years, the unique capabilities of ctDNA have attracted much attention and been widely studied. In this paper, based on the summary of the source, properties and sample processing of ctDNA, its detection technology and application in cancer diagnosis and treatment are reviewed. The roles and importance of ctDNA reference material in second-generation sequencing are described. The urgency of establishing uniform standards and specifications of ctDNA in various processes, such as samples collection, storage, quantitative testing and data analysis, has been pointed out.

Objective To predict the mechanism of Danhong injection in acute myocardial infarction based on network pharmacology and molecular docking.Methods The chemical ingredients of Danhong injection were collected by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),while Swiss Target Prediction was used to predict the corresponding targets of ingredients.The targets of acute myocardial infarction were retrieved in human gene database(GeneCards),online Mendelian inheritance in man(OMIM)and gene-disease association database(DisGeNET).Venny 2.1 online software was used to obtain the common targets of drugs-disease,and then the"drug-compound-target-disease"network diagram was constructed by using the software Cytoscape 3.8.2.The STRING database was used to draw the protein-protein ineraction network,and the perform gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out through the database for annotation,visualization,and integrated discovery(DAVID),and the AutoDock platform was applied in verifying the molecular docking of active components and protein targets.Results The 63 active components of Danhong injection could regulate 137 targets and 132 pathways to treat acute myocardial infarction.Przewaquinone C,luteolin,baicalein,sclareol,kaempferol,quercetagetin and other active compounds,which could mediate C-type lectin receptor,tumor necrosis factor,endocrine resistance,prolactin,phosphatidylinositol-3-kinases-serine/threonine protein kinase,Janus-activated kinase singal transducers and activators of transcriprion and other signaling pathways through tumor necrosis factor,RAC-alpha serine/threo-nine protein kinase,interleukin-1 beta,steroid receptor coactivator,mitogen-activated protein kinase 3,signal transducer and activator of transcription 3 and other key target proteins.The result of molecular docking showed that the targets and the components had a certain degree of binding.Conclusion Danhong injection can participate in the treatment of acute myocardial infarction through multiple components,targets and pathways,which provides a theoretical basis for the clinical application of Danhong injection and the mechanism of its treatment of acute myocardial infarction.

Objective To investigate the role of miR-27a-3p in sevoflurane-induced neurocognitive dysfunction.Methods Bioinformatics prediction and validation:Predicted the target genes of miR-27a-3p using bioinformatics databases,and verified the interaction between miR-27a-3p and target genes using dual-luciferase reporter gene assay and Western blot.Cell experiments:Cells were divided into two groups,the miR-27a-3p interference control(Sevo+NC)group was transfected with miR-27a-3p interference control plasmid,and the miR-27a-3p interference treatment(Sevo+anti-miR-27a-3p)group was transfected with miR-27a-3p interference plasmid.Before transfection,the plasmids were treated with 4％sevoflurane for 6 h.Western blot was used to detect the protein expression levels of tau and phosphorylaed tau(p-tau)in SY5Y cells of each group.Animal experiments:Mice were randomly divided into control group(no treatment),sevoflurane group(treated with 4％sevoflurane only),miR-27a-3p interference control group(Sevo+NC,injected with miR-27a-3p interference control plasmid after 4％sevoflurane treatment)and miR-27a-3p interference treatment group(Sevo+anti-miR-27-3p,injected with miR-27a-3p interference plasmid after 4％sevoflurane treatment).The neurocognitive abilities of mice were tested using the water maze experiment,and the level of tau phosphorylation in the hippocampal tissue of mice was detected by immunofluorescence.Results Bioinformatics prediction and validation:Bioinformatics prediction suggested that presenilin 1(PSEN1)might be a target gene of miR-27 a-3p.Dual-luciferase reporter gene assay and Western blot showed that miR-27 a-3p interacted with PSEN1.Cell experiments:The levels of p-tau in Sevo+NC group and Sevo+anti-miR27-3p group were 0.69±0.08 and 0.21±0.05,respectively.Animal experiments:The escape latency times of the control group,sevoflurane group,Sevo+NC group and Sevo+anti-miR-27-3p group were(27.54±3.67),(52.38±6.12),(55.16±5.79)and(38.46±4.78)s,respectively;the results of the novel object exploration index were 0.78±0.11,0.31±0.07,0.33±0.06,and 0.57±0.08,respectively.Immunofluorescence detection showed a significant decrease in p-tau levels in the hippocampal tissue of mice(P＜0.05).Conclusion miR-27 a-3p regulates the p-tau protein by targeting the PSEN1 gene,and interfering with miR-27 a-3p can alleviate sevoflurane-induced neurocognitive dysfunction in mice.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Objective:To explore the impact of rehabilitation exercise intervention mode based on cardiac function classification on clinical effect and quality of life(QOL)in patients with chronic heart failure(CHF).Methods:A total of 160 CHF patients who visited our hospital from Dec 2021 to Jan 2023 were selected,and 154 cases were fi-nally enrolled.According to the random number table method,patients were divided into study group and control group with 77 cases in each group.Control group received routine nursing program,while the study group received rehabilitation exercise intervention based on cardiac function classification on the basis of control group,both groups were intervened for three months.Clinical total effective rate,and cardiopulmonary function,serum oxidative stress indicators and MLHFQ score before and after intervention were compared between two groups.Results:Total effective rates of study subgroups of class Ⅱ and Ⅲ were significantly higher than those of control group(class Ⅱ:100.00％vs.83.78％;class Ⅲ:97.37％vs.80.00％)(P＜0.05 both).Compared with control subgroup of classⅢ after intervention,there were significant rise in peak VO2[(16.98±2.03)ml·min-1·kg-1 vs.(18.61±2.41)ml·min-1·kg-1],LVEF[(41.73±4.53)％vs.(48.03±5.22)％]and 6MWD[(351.34±61.00)m vs.(391.53±64.42)m](P＜0.01 all);and significant reductions in LVEDd[(57.55±3.91)mm vs.(53.18±3.07)mm],LVESd[(35.90±2.91)mm vs.(30.50±2.67)mm],levels of LPO[(6.00±0.99)mg/L vs.(3.95±0.61)mg/L],MPO[(3.83±0.58)mg/L vs.(2.03±0.28)mg/L],and MLHFQ total score[(57.05±4.57)points vs.(45.29±3.94)points]in study subgroup of class Ⅲ(P=0.001 all).Compared with control subgroup of class Ⅱ after intervention,there were significant rise in peak VO2,LVEF and 6MWD,and significant reductions in LVEDd,LVESd,levels of LPO,MPO and MLHFQ score in study subgroup of class Ⅱ,P＜0.05 or＜0.01.There was no significant difference in the incidence rate of adverse events during follow-up between two groups(3.90％vs.6.49％,P=0.717).Conclusion:Rehabilitation exercise intervention based on cardiac function classifi-cation can significantly improve cardiopulmonary function,inhibit oxidative stress response in vivo and improve quality of life in CHF patients,which is worthy of promotion and application in clinical practice.