BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

The observation of eye expression is an important aspect of traditional Chinese medicine diagnosis.Traditional Chinese medicine proposes the original proposition that"the eyes are the messenger of the heart",suggesting that eye expression reflects the external manifestation of mental consciousness and cognitive activities.Research has shown that eye expression can directly reflect brain function and cognitive abilities,serving as a biological marker for pathological changes in brain structure and playing an important role in early diagnosis of mental disorders.In recent years,scholars have paid increasing attention to eye tracking technology as an objective tool for measuring eye expression.This paper outlines the theoretical basis of using traditional Chinese medicine's observation of eye expression for diagnosing mental disorders,and analyzes the current application status of eye tracking technology in diagnosing conditions such as depression,schizophrenia,and autism spectrum disorder.It is hoped that this review will provide insights for future research on applying objective methods to traditional Chinese medicine diagnosis through observing eye expressions.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

OBJECTIVE To explore the relationship between levels of peripheral blood interleukin(IL)-6,IL-18,IL-1β,tumor necrosis factor(TNF-α),procalcitonin(PCT),C-reactive protein(CRP)and vascular cell adhesion molecule-1(VCAM-1)and disease condition and prognosis in children with Mycoplasma pneumoniae pneumonia(MPP),and to construct a prediction model.METHODS A total of 196 children with MPP admitted to Dazhou Central Hospital in Sichuan Province from Jan.2022 to Jan.2024 were selected as the MPP group and were divided into the mild group(n=124)and the severe group(n=72)according to the clinical pulmonary infection score(CPIS),and 200 healthy children who participated in physical examination in the hospital during the same period were selected as the healthy group.All 196 children with MPP received relevant treatments and were divided into a poor prognosis group(n=40)and a good prognosis group(n=156)according to their prognosis.The levels of peripheral blood IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 were measured in all the subjects,the risk factors affecting the disease condition and prognosis of children with MPP were analyzed,the prediction model was constructed,and the receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated to evaluate the predictive effect of the constructed prediction model.RESULTS Peripheral blood IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 levels in the MPP group were higher than those in the healthy group(P＜0.05).The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in peripheral blood were significantly higher in the severe group than those in the mild group(P＜0.05).IL-6(OR=1.203),IL-18(OR=1.072),IL-1β(OR=4.060),TNF-α(OR=1.264),PCT(OR=3.132),CRP(OR=1.546)and VCAM-1(OR=1.009)were risk factors for severe condition in MPP children(P＜0.05).The prediction model constructed for the devel-opment of severe illness in MPP children was as follows:Logit(P)=-67.522+0.185×IL-6+0.069×IL-18+1.401×IL-1β+0.234×TNF-α+1.142×PCT+0.436×CRP+0.009 ×VCAM-1.The AUC of the prediction model for predicting severe conditions in MPP children was 0.985.The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in peripheral blood in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).IL-6(OR=1.083,95％CI:1.024-1.145,P=0.005),TNF-α(OR=1.083,95％CI:1.002-1.172,P=0.046)and VCAM-1(OR=1.029,95％CI:1.015-1.044,P＜0.001)were risk factors for poor prognosis in MPP children.The prediction model established for poor prognosis in children with MPP was as follows:logit(P)=-31.557+0.080×IL-6+0.080×TNF-α+0.029×VCAM-1.The AUC of the prediction model for predicting poor prognosis in MPP children was 0.979.CONCLUSIONS The levels of IL-6,IL-18,IL-1β,TNF-α,PCT,CRP and VCAM-1 in pe-ripheral blood are closely related to the severity of illness in children with MPP.The prediction model constructed on the basis of the above indicators predicts the risk of severe disease in children with MPP,and the prediction model constructed on the basis of IL-6,TNF-α and VCAM-1 predicts the risk of poor prognosis in children with MPP.

The observation of eye expression is an important aspect of traditional Chinese medicine diagnosis.Traditional Chinese medicine proposes the original proposition that"the eyes are the messenger of the heart",suggesting that eye expression reflects the external manifestation of mental consciousness and cognitive activities.Research has shown that eye expression can directly reflect brain function and cognitive abilities,serving as a biological marker for pathological changes in brain structure and playing an important role in early diagnosis of mental disorders.In recent years,scholars have paid increasing attention to eye tracking technology as an objective tool for measuring eye expression.This paper outlines the theoretical basis of using traditional Chinese medicine's observation of eye expression for diagnosing mental disorders,and analyzes the current application status of eye tracking technology in diagnosing conditions such as depression,schizophrenia,and autism spectrum disorder.It is hoped that this review will provide insights for future research on applying objective methods to traditional Chinese medicine diagnosis through observing eye expressions.

Type 2 diabetes mellitus is a metabol-ic disease characterized by high blood sugar levels.Traditionally,amino acids are primarily viewed as the basic building blocks for proteins and peptide synthesis.However,in recent years,amino acids have gained increased attention as signaling mole-cules that play crucial roles in the maintenance and regulation of metabolic homeostasis.It has been found that there is a close correlation between the metabolism of branched-chain and/or aromatic amino acids and the occurrence or development of type 2 diabetes mellitus.Furthermore,there have been successive reports on the regulation mecha-nism involved.This article will focus on the meta-bolic processes,mechanisms and clinical value of branched-chain and aromatic amino acids in type 2 diabetes mellitus.It will also summarize and pro-vide an outlook on the current state of amino acid metabolism in the treatment of diabetes mellitus,with the aim of offering new ideas for the treat-ment of type 2 diabetes mellitus.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

Objective To investigate the analgesic effect of combined spinal-epidural analgesia and its impact on stress levels in multiparous women during labor in a high-altitude region.Methods A total of 86 multiparous women were enrolled as study subjects.They were divided into observation group(43 cases)and control group(43 cases)based on whether they received labor analgesia.The obser-vation group received combined spinal-epidural analgesia during the first stage of labor.Pain levels[Visual Analogue Scale(VAS)],labor psychological experience[Chinese version of the Childbirth Self-Efficacy Inventory(CBSEI-C32)and Coping with Childbirth(CCB)],stress levels[serum cor-tisol(Cor),norepinephrine(NE)and adiponectin(APN)]as well as maternal and neonatal out-comes were compared between the two groups.Results The VAS scores during the first,second and third stages of labor were significantly lower in the observation group than those in the control group(P＜0.05).The CBSEI-C32 and CCB scores at 24 hours postpartum in the observation group were significantly higher than those in the control group(P＜0.05).The serum levels of Cor,NE and APN at 12 hours postpartum in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of adverse maternal and neonatal outcomes in the observation group was 0％,which was significantly lower than 9.30％in the control group(P＜0.05).Con-clusion In high-altitude regions,combined spinal-epidural analgesia is effective in reducing labor pain,improving labor psychological experience,lowering stress levels,and reducing adverse maternal and neonatal outcomes in multiparous women.

Objective The objective of this study was to investigate the effects of maytansine on proliferation,migration,in-vasion,apoptosis and autophagy of human thyroid cancer C643 cells.Methods C643 cells were treated with different concentrations(0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L)of maytansine,the effect of maytansine on the proliferation of C643 cells was detected by the sulforhodamine B(SRB)method,and the concentration of subsequent experiments was determined.C643 cells in the logarithmic growth stage period were divided into the control group,low-dose group,mid-dose group and high-dose group.The effects of maytansine on migration and invasion abilities of C643 cells were detected by cell scratch and Transwell chamber assay;The levels of reactive oxygen species(ROS)were detected by 2′,7′-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe experi-ment;The apoptosis rate of C643 cells was detected by flow cytometry;The expression of proteins related to apoptosis or autophagy was detected by Western blot.Results Maytansine at concentrations of 0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L could in-hibit the proliferation of C643 cells(P<0.05),and exhibited a significant concentration time dependence.The half maximal inhibitory concentrations(IC50)at 24,48 and 72 h were 54.255,5.193 and 0.647 μmol/L,respectively;The cell scratch and Transwell chamber results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could reduce the migration and invasion abilities of C643 cells(P<0.05 and P<0.01).The fluorescence probe results showed that maytansine at concentrations of 0.1,1 and 10μmol/L could increase the intracellular ROS levels of C643 cells(P<0.01).The flow cytometry results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could concentration dependently increase the apoptosis rate of C643 cells(P<0.01).The Western blot results showed that with the increase of maytansine concentrations,the expression of Bax protein related to apoptosis in C643 cells increased(P<0.05),the expression of Bcl-2 decreased(P<0.05),the expression of LC3Ⅱ/Ⅰ(P<0.05)and Beclin-1(P<0.01)increased,while the expression of p62 decreased(P<0.001).Conclusion Maytansine can inhibit the proliferation,migration and invasion of human thyroid cancer C643 cells,and induce the synergistic effect on apoptosis and autophagy by increasing intracellular ROS levels.

Type 2 diabetes mellitus is a metabol-ic disease characterized by high blood sugar levels.Traditionally,amino acids are primarily viewed as the basic building blocks for proteins and peptide synthesis.However,in recent years,amino acids have gained increased attention as signaling mole-cules that play crucial roles in the maintenance and regulation of metabolic homeostasis.It has been found that there is a close correlation between the metabolism of branched-chain and/or aromatic amino acids and the occurrence or development of type 2 diabetes mellitus.Furthermore,there have been successive reports on the regulation mecha-nism involved.This article will focus on the meta-bolic processes,mechanisms and clinical value of branched-chain and aromatic amino acids in type 2 diabetes mellitus.It will also summarize and pro-vide an outlook on the current state of amino acid metabolism in the treatment of diabetes mellitus,with the aim of offering new ideas for the treat-ment of type 2 diabetes mellitus.