Objective To investigate the expression of blood basophil activation markers in patients with allergic rhinitis (AR) and the effects of allergens on their expression. Methods The blood samples were collected from the following four groups: healthy control (HC), AR patients with negative skin prick test (nAR), seasonal AR patients (sAR) and perennial AR patients (pAR). Flow cytometry was employed to analyze the expression of basophil activation markers Immunoglobulin E receptor I alpha(FcepsilonRIα), CD63 and CD203c in AR patients. Plasma levels of interleukin 4 (IL-4) and IL-8 were measured by liquid-phase chip technology, and their correlations with the percentages of activated basophils were further analyzed. An ovalbumin-induced AR mouse model was established, and the expression levels of FcepsilonRIα and CD63 on blood basophils were detected. Results The expression of FcepsilonRIα, CD203c and CD63 on basophils were increased in nAR, sAR and pAR patients. Allergens enhanced the mean florescence intensity expression of CD63 and CD203c on basophils of sAR and pAR patients. The plasma levels of IL-4 and IL-8 were elevated in nAR, sAR and pAR patients, showing moderate to high correlations with the expression levels of basophil activation markers. The FcepsilonRIαand CD63 expression on basophils of AR mice were increased. Conclusion Allergens may contribute to AR pathogenesis by upregulating the expression of FcepsilonRIα, CD63 and CD203c, as well as promoting the secretion of IL-4 and IL-8.
Basophils/metabolism* ; Humans ; Allergens/immunology* ; Animals ; Rhinitis, Allergic/blood* ; Female ; Male ; Adult ; Mice ; Biomarkers/blood* ; Tetraspanin 30/blood* ; Interleukin-4/blood* ; Interleukin-8/blood* ; Receptors, IgE/blood* ; Phosphoric Diester Hydrolases ; Young Adult ; Pyrophosphatases ; Middle Aged ; Mice, Inbred BALB C

Objective To investigate how culture duration affects the expression of immune membrane proteins in human monocyte-derived dendritic cells (DCs) and their exosomes (DEXs). Methods Human monocytes were induced with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to differentiate into DCs and were subsequently matured with tumor necrosis factor α(TNF-α). Exosomes were isolated by ultracentrifugation, and DEXs were identified by transmission electron microscopy and Amnis imaging flow cytometry, which were also used to quantify the expression of immune membrane proteins on DCs and DEXs. Results On the 10th day of culture, DCs displayed high surface expression of CD11c, CD80, CD86, major histocompatibility complex class I (MHC-I), and MHC-II. Expression peaked at day 18(CD11c: 78.66%±20.33%, CD80: 76.41%±10.02%, CD86: 96.43%±0.43%, MHC-I: 84.71%±2.96%, MHC-II: 80.01%±7.03%). After day 24, the overall expression showed a declining trend, with statistically significant differences observed for all markers except CD80 and MHC-II. By day 30, 80% of the DCs still expressed CD80, CD86, and MHC-II. The expression of immune membrane proteins on DEX surfaces also reached its peak on day 18, followed by an overall decline with prolonged culture time, with statistically significant differences observed for all markers except CD80. Correlation analysis revealed a significant positive relationship between the expression levels of immune membrane proteins on DC and DEX surfaces (CD11c: r=0.98; CD80: r=0.65; CD86: r=0.82; MHC-I: r=0.86; MHC-II: r=0.93). Conclusion Human monocyte-derived DCs in vitro express high expression of immune membrane proteins and maintain stable expression over a specific period. The exosomes secreted by these cells similarly demonstrate high surface expression of immune membrane proteins, with temporal trends aligned with those of the parent DCs.
Humans ; Dendritic Cells/immunology* ; Exosomes/immunology* ; Monocytes/metabolism* ; Cells, Cultured ; Time Factors ; B7-1 Antigen/metabolism* ; Membrane Proteins/immunology* ; Cell Culture Techniques/methods* ; B7-2 Antigen/metabolism* ; Cell Differentiation ; CD11c Antigen/metabolism* ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology*

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

With the rapid development of artificial intelligence(AI),how to digitize the teaching of Medical Immunology is a new challenge posed by the times and education.This study is based on the advanced teaching model of Medical Immunology,which includes lectures-PAD class-flipped classrooms-expert lecture.By introducing knowledge mapping and AI teaching assistant into the entire learning process,the students not only deepen their understanding of the knowledge system of Medical Immunology,but also ex-ercise their ability to apply immunological knowledge to solve practical clinical problems,enhance their self-learning ability,expres-sion ability,communication ability,on-site performance ability,and cultivate a spirit of unity,cooperation,and exploration.The practice of empowering Medical Immunology teaching with digital intelligence achieves the integration of theory and application,the linkage between in class and out of class teaching,the connection between commonalities and individualities,and the union of abili-ties and qualities in Medical Immunology teaching.It also provides practical basis for exploring the implementation path of digital intel-ligence empowerment in Medical Immunology teaching.

Background and purpose:Melanoma is a highly invasive malignant tumor originating from melanocytes,which poses a great threat to human life and health around the world,and its morbidity and mortality have been rising continuously in recent years.Telomerase and autophagy play crucial roles in cell proliferation,survival and stress response.Telomerase maintains the replication ability of cells by prolonging telomeres at the ends of chromosomes,and autophagy,as a self-degradation mechanism of cells,can not only help cells remove damaged components to promote survival,but also induce cell death under certain conditions.In the tumor environment,they are often abnormally activated or out of balance,and participate in the occurrence and development of many cancers,including melanoma.This study investigated the roles of telomerase and autophagy in melanoma progression and evaluated the potential synergistic therapeutic effects of combined application of telomerase inhibitor BIBR1532 and autophagy inhibitor chloroquine(CQ)in melanoma treatment.Methods:Malignant melanoma cells A375 were treated with telomerase inhibitor BIBR1532.The cell viability was assessed using the cell counting kit-8(CCK-8)assay,and the cell apoptosis was detected using the Annexin Ⅴ/propidium iodide(PI)double staining method.Additionally,the expressions of autophagy-related proteins LC3-Ⅱand p62 were detected by Western blot,and the changes in autophagy flux were observed using dual-tagged adenovirus transfection technology.Based on these studies,BIBR1532 and the autophagy inhibitor CQ were further applied in combination to analyze cell proliferation,apoptotic rate,changes in mitochondrial membrane potential,and cell cycle distribution,and the cloning formation experiment was used to verify the cell's proliferative capacity,thereby comprehensively evaluating the efficacy of this combined treatment strategy.Results:Telomerase inhibitor BIBR1532 at a concentration of 50 μmol/L significantly inhibited the growth of malignant melanoma cells A375 and induced apoptosis.At the same concentration,BIBR1532 upregulated the expression of the autophagy-related protein LC3-Ⅱ in A375 cells,while downregulating the expression of p62 protein.By transducing A375 cells with a dual-tagged adenovirus,it was observed that autophagy flux was significantly enhanced after treatment with BIBR1532.Furthermore,the combined application of BIBR1532(50 μmol/L)and the autophagy inhibitor CQ(20 μmol/L)significantly promoted the death of A375 cells,induced apoptosis and destruction of mitochondrial membrane potential,caused cell cycle arrest at the G2/M phase,and significantly inhibited the cell's clonogenic ability.Conclusion:Telomerase inhibitor BIBR1532 not only inhibits the proliferation of malignant melanoma cells but also activates the autophagy process in these cells,and inhibition of the autophagy response by autophagy inhibitor CQ can enhance the sensitivity of malignant melanoma cells to telomerase inhibitor BIBR1532.

Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.

Objective:To analyze the current status of the standard system construction for smart health and elderly care in China,analyze the framework of the standard system,and propose policy recommendations for the construction of the standard system.Methods:The standard system of smart health and elderly care were searched on the websites of the State Council of China,the National Standard Information Public Service Platform,and the sub-websites of national,industry,local,group,and enterprise standards.Policy text analysis was used to explore the current status and framework of standard system construction.Results:Currently,67 standards related to smart health and elderly care in China were included,including 0 national standards,2 industry standard,10 local standards,31 group standards,and 24 enterprise standards.These standards formed a subsystem that covered general,data,product,platform,and service standards.Conclusion:The construction of the standard system of smart health and elderly care in China has achieved certain results,but there are still shortcomings,and it is necessary to strengthen the top-level design and build a perfect framework of the standard system.

Objective To explore the diagnostic value of ultrasonography in ischiofemoral impinge-ment syndrome(IFI).Methods Fifty-six patients who underwent hip MRI with confirmed IFI diagnosis and completed ultrasonography examinations were enrolled as the IFI group,including 44 females and 12 males.Twenty healthy volunteers were concurrently recruited as the control group,consisting of 10 females and 10 males.The control group underwent ultrasonography examinations of bilateral hip joints,whiletheischialfemoralspace(IFS)andquadratusfemoristhickness(QFT)of both groups were measured and recorded.Then measurements were compared within(by laterality and gender)and between the two groups using independent-samples t-tests.Moreover,receiver operating characteristic adults,males exhibited significantly higher IFS and QFT values than females(P<0.05).Within the IFI group,males with affected hips had significantly higher IFS than females(P<0.05),while no sig-nificant differences were observed in QFT between different genders(P>0.05).Moreover,affected hips in the IFI group showed significantly narrower IFS and thicker QFT compared to both contralateral hips and the control group(P<0.001).In addition,the diagnostic cut-off values of IFS and QFT for ultrasound diagnosis of IFI were 22.93 mm and 16.48 mm,respectively.At these thresholds,the ar-eas under the curve(AUC)were 0.997 and 0.977,with sensitivities of 97.8%and 91.8%,and speci-ficities of 98.4%and 97.8%,respectively.Conclusion Ultrasound can serve as a reliable diagnostic technique for IFI,where narrowing of the IFS and thickening of the QFT should raise suspicion of this condition.