ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective To establish in vitro the small intestinal organoid culture system and to investigate the effect of lipopolysaccharide(LPS)on the growth of small intestinal organoids and the secretion of inflammatory factors.Methods In vitro,the small intestinal crypt cell mass of C57BL/6 mice was aseptically isolated,collected and embedded in organoid matrix.Under the support of complete medium,the small intestinal organoids with three-dimensional multi-leaf structure with small intestinal epithelioid structure were formed.The small intestinal organoids were subcultured after 5-7 d culture.On the third day after passage,the small intestinal organoids were randomly divided into different mass concentrations of LPS groups(0,150,175,200,225,250,275 and 300 mg/L).After 24 h and 48 h of LPS induction,morphological changes of small intestinal organoid growth and differentiation were observed.CCK-8 method was used to detect the effect of different time points and mass concentrations of LPS on the proliferative activity of small intestinal organoids after induction of inflammation.The effects of four different mass concentrations of LPS(0,175,200 and 225 mg/L)on expression levels of granulocyte-macrophage colony stimulating factor(GM-CSF),interleukin(IL)-1α,IL-6 and IL-10 in organoid culture supernatant at different times were detected by enzyme-linked immunosorbent assay(ELISA).Results The mouse small intestinal organoid culture system was preliminarily constructed.After different time and mass concentration of LPS induced inflammation of small intestinal organoids,it was observed by morphology that small intestinal organoids would have different degrees of expansion and apoptosis in lumen.The proliferation,differentiation and budding of damaged intestinal epithelial crypts or intestinal stem cells were also inhibited to varying degrees,indicating that the growth of small intestinal organoids would be limited to varying degrees after induced inflammation.The proliferation activity of small intestinal organoids decreased to varying degrees after 24 h and 48 h of LPS induction at 175-225 mg/L(P＜0.05),but the cell viability was still greater than 50%.The levels of IL-1α,IL-6 and GM-CSF partially increased after induction with 200 mg/L and 225 mg/L LPS for 24 h and 48 h(P＜0.05).The level of IL-10 decreased after induction with 200 mg/L LPS for 24 h and 48 h(P＜0.05).Conclusion In this study,a model of intestinal inflammatory injury in vitro induced by LPS with different mass concentrations and time points is preliminarily constructed,which provides a more reliable research platform for the mechanism research of intestinal diseases and the screening of effective drugs in the future.

Objective To analyze the risk factors for severe illness caused by coronavirus disease 2019 in Fuzhou city.Methods The data of 4081 confirmed cases with current address in Fuzhou was collected from China Information System for Disease Control and Prevention from January 1 to June 30,2023.The epidemiological data of those cases was investigated such as the demographic characteristics,clinical manifestations and past medical history,etc.The risk factors of severe cases were analyzed by using the logistic regression.Results 4081 confirmed cases had been reported including 671 severe cases and 3410 non-severe cases.The demographic characteristics of severe cases,such as the proportion of male,age and current address in community were higher than that of non-severe cases,vaccination rate was lower than non-severe cases(59.02%vs.80.12%),the differences are statistically significant(P＜0.001).The clinical manifestations such as interval time between onset and visit(P=0.001),fever(P=0.002),difficulty in breathing/shortness of breath(P=0.001)were the factors related to severe illness.The past medical histories such as history of chronic lung disease,history of heart cerebrovascular disease of severe cases,were higher than that of non-severe cases(P＜0.001).Multivariate logistic regression showed that the male,the higher age,current address in community,no vaccination,the longer interval time between onset and visit,fever,difficulty in breathing/shortness of breath,the history of chronic lung disease,the history of heart cerebrovascular disease raised the risk of becoming severe cases.The healing time for severe cases was longer than that for non-severe cases(P＜0.001).Conclusion Sex,age,current address,vaccination,interval time between onset and visit,fever,difficulty in breathing/shortness of breath,history of chronic lung disease,and history of heart cerebrovascular disease are the influencing factors for severe illness.

【Objective】 To investigate the correlation between heart rate variability (HRV) and the degree of nervousness before blood donation. 【Methods】 The psychological state of 253 blood donors before blood donation was assessed by the self-rating anxiety scale (SAS) and the degree of nervousness and their HRV were measured. The correlation between the SAS score, the degree of nervousness and the HRV parameters was analyzed, and the differences were compared among different types of donors by multivariate linear regression. 【Results】 A total of 247 blood donors were included in the study. Five HRV parameters in blood donors aged 18-24 were higher than in those aged 25 years and above(all P<0.05), and the anxiety level was higher in female donors(SAS score 41-46) than in males(SAS score 35-43)(P<0.001); the pre-donation SAS score was consistent with the assessment of the tension level (r=0.970, P<0.001); the pre-donation tension level and the SAS score were all significantly negatively correlated with VLF in HRV parameters(r=0.179, P=0.005), and the associations were independent of confounders such as age, body mass index and gender (P<0.05). 【Conclusion】 Compared with SAS and tension assessment, HRV is more objective, and can be used as one of the tests for assessing the tension level of blood donors. The inclusion of HRV in the routine screening of blood donors deserves further study for its application in assessing the anxiety level of blood donors before blood donation, identifying people prone to blood donation-related vasovagal reaction (DRVR), preventing and reducing the risk of DRVR, and improving the safety of blood donation.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

The concept and harms of hypothermia were introduced.The research progress of the intelligent warning equipment and model for hypothermia was reviewed,and the advantages and problems in practical application were analyzed.It's pointed out the intelligent warning equipment had to be improved in environmental adaptability,operational convenience and functio-nal stability and the model be enhanced in robustness,large-scale clinical validation and warning parameter accessibility.[Chinese Medical Equipment Journal,2024,45(5):86-94]

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Objective To explore the efficacy of high tibial osteotomy(HTO)combined with medial meniscus centraliza-tion in knee osteoarthritis.Methods A total of 26 patients who underwent surgery from October 2018 to October 2020 were re-viewed.Among them,14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group,including 8 males and 6 females,with an average age of(50.2±1.4)years old and follow-up time of(16.8±4.0)months.Twelve patients with high tibial osteotomy were in the control group,including 6 males and 6 females,with an average age of(50.9±1.8)years and follow-up time of(19.0±4.8)months.Operation time,the knee Lysholm score,knee 2000 IKDC score,MRI,femoral tibial angle(FTA),hip knee ankle angle(HKA),and intraoperative and postoperative compli-cations were recorded.Results All the incisions healed without any complication.The operation time in the centralized group was longer than that in the control group[(65.0±2.1)min vs(52.0±2.1)min,P＜0.05].The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[(2.8±1.4)mm vs(1.1±2.2)mm,P＜0.05].The FTA,HKA,knee Lyshlom score,and 2000 IKDC score between two groups were no significantly(P＞0.05).Postop-erative knee Lyshlom score and knee 2000 IKDC score improved in both groups(P＜0.05).Conclusion HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function.The medium and long-term curative effect still needs long-term follow-up of more cases.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.