Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective: To explore the relationship between sedentary behavior with cardiorespiratory fitness and executive function in adolescents, and to provide some references for sedentary behavior prevention and executive function improvement. Methods: From September to December 2022, a total of 5 018 adolescents aged 13 to 18 years were selected by stratified random sampling method in Shanghai, Suzhou, Taiyuan,Wuyuan, Xingyi, and Urumqi to conduct physical activity survey, as well as cardiorespiratory fitness and executive function assessment. Pearson s correlation was used to analyze the relationship between sedentary behavior, cardiorespiratory fitness and executive function. The mediation effect model was fitted by the bootstrap mediation procedure in the PROCESS (version 3.3 ) SPSS macro compiled by Haves, and the mediation effect of adolescents cardiorespiratory fitness in the relationship between static behavior and executive function was examined using model 4 in the PROCESS SPSS macro, where Boosrap method was used to compute the mediation effect of adolescents cardiorespiratory fitness. where the Boosrap method was used to calculate confidence intervals for the mediating effects. Results: Adolescents daily sedentary time was positively correlated with both the refreshing function (1-back and 2-back) and the switch function reaction time ( r =0.05, 0.07, 0.05, P <0.01). Adolescent VO 2max was negatively correlated with both the refreshing function (1-back,2-back) and the switching function ( r =-0.09, -0.14 , -0.11, P <0.01). Adolescents daily sedentary time was negatively correlated with VO 2max ( r =-0.04, P <0.01); cardiorespiratory fitness mediated effect values between sedentary behavior and refreshing function (1-back and 2-back) and converted function were 0.20(95% CI =0.06-0.36), 0.43(95% CI =0.14-0.74) and 0.13 (95% CI =0.04-0.22), with mediating effect shares of 6.87%, 8.33% and 8.59%, respectively. Conclusion The duration of sedentary behavior in adolescents is related to executive function performance, and cardiorespiratory fitness may serve as a mediator to mediate the association between sedentary behavior and executive function in adolescents.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective:An artificial intelligence(AI)model based on deep learning algorithms was constructed using clinical data to evaluate the feasibility of predicting the efficacy of neoadjuvant immunotherapy combined with chemotherapy for non-small cell lung cancer(NSCLC).Methods:Clinical and pathological data of 132 patients with NSCLC who were diagnosed and treated with neoadjuvant immunotherapy combined with chemotherapy between January 2020 and January 2024 at Beijing Chest Hospital/Beijing Tuberculosis and Thoracic Tumor Research Institute were collected.Statistical analysis was conducted to identify the main factors affecting the efficacy of neoadjuvant im-munotherapy combined with chemotherapy.Variables were selected based on statistical results and relevant literature,and a variable data-set was constructed.A deep learning model was established using a multi-layer perceptron(MLP)algorithm with 5-fold cross-validation,and the performance of the model was evaluated using receiver operating characteristic curve(ROC).Results:Among the 132 patients,univari-ate analysis demonstrated statistically significant differences in sex(P=0.020),smoking history(P=0.004),carcinoembryonic antigen(CEA)(P=0.038)and programmed death-ligand 1(PD-L1)≥1%(P=0.038)between the major pathological response(MPR)and non-MPR groups.Patients in the complete pathological response(pCR)group and non-pCR groups showed statistical differences in tumor size(P=0.007)and CEA levels(P=0.010).After 5-fold cross-validation,the average area under the curve(AUC)of the MPR prediction model in the validation and test sets was 0.72 and 0.71,respectively.Conclusions:The deep learning model can effectively predict the efficacy of neoadjuvant chemoim-munotherapy in patients with NSCLC.

Objective:To assess the reliability,and validity of the Chinese version of a short-form of Health Literacy Dental scale(HeLD-14)in 3-6 years old preschool children's parents.Methods:The study population consisted of those eligible 3-6 years old preschool children's parents in Yanqing Dis-trict,Beijing,China in 2021.A total of 1 479 preschool children's parents were surveyed by question-naire to understand the general situation of parents and oral health literacy related content.SPSS 21.0 and Mplus 7.4 were used for statistical analysis.Through Cronbach's α coefficient,confirmatory factor a-nalysis,Pearson correlation calculation,Student's t test and other methods,the internal consistency reli-ability,structure validity,calibration validity and discrimination validity of the scale were evaluated.Re-sults:The Cronbach's α coefficient of Chinese version HeLD-14 scale was 0.958,and Cronbach's α co-efficient of different constructs ranged from 0.778 to 0.963.The confirmatory factor analysis showed that the factor loadings of each item of the Chinese version HeLD-14 scale were between 0.719 and 0.977(P＜0.001),root-mean-square error of approximation(RMSEA)=0.04,comparative fix index(CFI)=0.992,Tucker-Lewis index(TLI)=0.988,and the model had good goodness of fit.The total score of the Chinese version HeLD-14 scale and the scores of the dimension of concerning,understanding,sup-porting,financial burden,medical treatment,communication,and application were all positively correla-ted with general self-efficacy,and the correlation coefficients were 0.439,0.406,0.370,0.344,0.346,0.367,0.373,0.390,respectively(P all＜0.05).For parents in the high group with the top 27％HeLD-14 score,the average HeLD-14 score was 69.27±1.06,which was higher than the low group with the bottom 27％HeLD-14 score,41.29±11.09(t=48.13,P＜0.01).Conclusion:The Chinese version HeLD-14 scale has good reliability and validity in the 3-6 years old preschool children's parents,and can be used as a tool to assess the oral health literacy of parents of preschool children.

AIM:To clarify the effect of macrophage PKM2 deficiency on mucosal repair in ulcerative colitis(UC).METHODS:The gene expression and metabolic profiles in UC patients were first analyzed based on the following databases:PXD001608,GSE193677,and GSE214695.Using the macrophage-specific PKM2 elimination mice(PKM2ΔMAC),the functions of PKM2 in dextran sulfate sodium(DSS)-induced UC were clarified in vivo by analyzing the body weight,disease activity index(DAI)scores,HE staining,immunohistochemical staining,and expression of muco-sal barrier markers.The impact of PKM2 on macrophage polarization was also investigated by flow cytometry,RNA se-quencing and RT-qPCR in mouse bone marrow-derived macrophages(BMDMs)and THP-1 cells in vitro.RESULTS:Bioinformatic analysis suggested that the intestinal tissues of UC patients preferred glycolysis.The expression of PKM was parallel to the severity of UC in patients,and the expression of PKM2,but not PKM1,was elevated in macrophages of UC mice.In the DSS-induced UC mice,macrophage-specific PKM2 elimination significantly alleviates the body weight loss,diarrhea,rectal bleeding,colonic shorten,as well as decreased DAI scores and mucosal tissue damage.The BMDMs de-rived from the PKM2ΔMAC mice preferred the M2 polarization upon LPS or IL-4 stimulation to that derived from the wild-type mice,as indicated by the F4/80+CD45+CD86+and F4/80+CD45+CD206+population,as well as the expression of Ocln,F11r and Tjp-1.The RNA sequencing results indicated significant gene differential expression in PKM2 knockout mouse macrophages,which was enriched in biological processes such as leukocyte migration,tissue remodeling,and cytokine in-teractions.Macrophage PKM2 deficiency promoted the expression of mucosal repair factors(Il8,Cxcl1,Ptgs2 and Wnt6),which was further validated in PKM2 knockout THP-1 cells.CONCLUSION:The PKM2 deficiency in macro-phages benifits the mucosal repair in UC status via facilitating the wound-healing macrophage polarization.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.