Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

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

Objective To mine and analyze the routine blood test data of children with allergic rhinitis (AR), identify routine blood parameters related to childhood allergic rhinitis, establish an effective diagnostic model, and evaluate the performance of the model. Methods This study was a retrospective study of clinical cases. The experimental group comprised a total of 1110 children diagnosed with AR at the First Affiliated Hospital of Air Force Medical University during the period from December 12, 2020 to December 12, 2021, while the control group included 1109 children without a history of allergic rhinitis or other allergic diseases who underwent routine physical examinations during the same period. Information such as age, sex and routine blood test results was collected for all subjects. The levels of routine blood test indicators were compared between AR children and healthy children using comprehensive intelligent baseline analysis, with indicators of P≥0.05 excluded; variables were screened by Lasso regression. Binary Logistic regression was used to further evaluate the influence of multiple routine blood indexes on the results. Five kinds of machine model algorithms were used, namely extreme value gradient lift (XGBoost), logistic regression (LR), gradient lift decision tree (LGBMC), Random forest (RF) and adaptive lift algorithm (AdaBoost), to establish the diagnostic models. The receiver operating characteristic (ROC) curve was used to screen the optimal model. The best LightGBM algorithm was used to build an online patient risk assessment tool for clinical application. Results Statistically significant differences were observed between the AR group and the control group in the following routine blood test indicators: mean cellular hemoglobin concentration (MCHC), hemoglobin (HGB), absolute value of basophils (BASO), absolute value of eosinophils (EOS), large platelet ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PLT), absolute values of leukocyte neutrophil (W-LCC), leukocyte monocyte (W-MCC), leukocyte lymphocyte (W-SCC), and age. Lasso regression identified these variables as important predictors, and binary Logistic regression further analyzed the significant influence of these variables on the results. The optimal machine learning algorithm LightGBM was used to establish a multi-index joint detection model. The model showed robust prediction performance in the training set, with AUC values of 0.8512 and 0.8103 in the internal validation set. Conclusion The identified routine blood parameters can be used as potential biomarkers for early diagnosis and risk assessment of AR, which can improve the accuracy and efficiency of diagnosis. The established model provides scientific basis for more accurate diagnostic tools and personalized prevention strategies. Future studies should prospectively validate these findings and explore their applicability in other related diseases.
Humans ; Male ; Female ; Rhinitis, Allergic/blood* ; Child ; Biomarkers/blood* ; Retrospective Studies ; Early Diagnosis ; Child, Preschool ; ROC Curve ; Logistic Models ; Hematologic Tests ; Algorithms ; Adolescent ; Machine Learning

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Background: The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB. Methods: We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy. Results: CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P = 0.002). Conclusions CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.

Objective To construct a predictive model for the risk of non-suicidal self-injury(NSSI)in young and middle-aged patients with major depressive disorder based on the decision tree algorithm.Methods Young and middle-aged patients with major depressive disorder admitted to the Chongqing Mental Health Center from January 2021 to June 2023 were selected as the research subjects and their clinical data were collected.According to whether NSSI occurred or not,the patients were divided into the NSSI group(n=72)and the non-NSSI group(n=82).Univariate and multivariate logistic regression analyses were used to analyze the risk factors of NSSI in young and middle-aged patients with major depressive disorder.A deci-sion tree predictive model was established based on the results of logistic regression analysis and the Chi-square Automatic Interaction Detection(CHAID)algorithm.The predictive value of the model was evaluated using Receiver Operating Characteristic(ROC)curve.Results The incidence of NSSI in 154 young and mid-dle-aged patients with major depressive disorder was 46.8％.The results of single-factor analysis showed that there were no statistically significant differences(P＞0.05)in gender,age,education level,occupation,family composition,only child status,relationship status,fertility status,main place of residence,family economic source,and housing conditions between the two groups.Statistically significant differences(P＜0.05)were observed in living conditions,family economic status,duration of depression,SSRS score,PSS-Fa score,and DS score between the two groups.Multi-factor logistic regression analysis showed that lower family economic lev-el,longer duration of depression,SSRS score＜20 points,PSS-Fa score＜6 points,and DS score ≥47.2 points were independent risk factors for NSSI in young and middle-aged patients with major depressive disorder(P＜0.05).The constructed decision tree model had five layers and ten nodes,with family economic situation,duration of depression,SSRS score,and PSS-Fa score selected as the nodes of the model,among which the PSS-Fa score was the most important predictive factor.ROC curve analysis showed that the AUC of the model was 0.881(95％CI:0.844-0.918).Conclusion There are many influencing factors for the occurrence of NSSI in young and middle-aged patients with major depressive disorder.The decision tree model constructed based on these factors has a high predictive value for the risk of NSSI in young and middle-aged patients with major depressive disorder.

Objective To investigate the clinical characteristics and dosimetric parameters associated with acute hematologic toxicity (AHT) resulting from radiation-induced damage to hematopoietic organs in patients undergoing chemoradiotherapy for cervical cancer and to provide a reference for establishing dose constraints in relevant regions of interest (ROIs) and predicting adverse tissue reactions during the development of clinical treatment plans. Methods A retrospective analysis was conducted on 556 patients with cervical cancer who underwent chemoradiotherapy at our hospital. Univariate (χ² and t-test) and multivariate (binary logistic regression analyses) methods were employed to investigate the association of clinical factors and pelvic dose-volume parameters with grade ≥ 3 AHT in patients with cervical cancer. Clinical factors comprised patients’ age, clinical stage, pathologic stage, whether the patient had received chemotherapy in the radiotherapy cycle of interest, and dose-volume dosimetric parameters V_x and D_mean for pelvic bone marrow (BM) and femoral head (FH) structures. Results The incidence of AHT among the included cases was 30.4% (169/556). Chi-square analysis of the clinical factors revealed that whether the patient had received chemotherapy, patient’s age, and pathologic stage had a significant impact on AHT. Univariate analysis showed that the factors associated with AHT were mean dose, V₅, V₁₀, V₁₅, V₂₀, and V₂₅ of BM and FH; dosimetric parameters such as V₃₅ of FH had a significant impact on the development of AHT. Multivariate logistic regression analysis identified V₁₅ of pelvic BM as an independent risk factor for AHT (P=0.041), with a threshold value of 84.29% as determined by a receiver operating characteristic (ROC) curve. Conclusion Whether a patient had received chemotherapy in the radiotherapy cycle of interest, and patient’s age and pathologic stage can serve as predictors of AHT. V₁₅ of BM is an independent risk factor for AHT development. Therefore, when formulating a treatment plan, it is crucial to ensure that pelvic V₁₅ remains below 84.29% to effectively reduce the incidence of grade ≥ 3 acute bone marrow depression.

Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Objective:To screen the interacting protein of ubiquitin-conjugating enzyme E2S(UBE2S)and construct the hepatocellular carcinoma(HCC)based on UBE2S interacting protein prognosis model(UIPM),and to discuss the value of UIPM in assessing the prognosis of the HCC patients.Methods:Co-immunoprecipitation(Co-IP)was used to screen the protein complexes binding to Flag-UBE2S.After validation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting methods;liquid chromatography-mass spectrometer(LC-MS)was used to identify the UBE2S interacting proteins;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted on these proteins;the prognosis-related proteins from The Cancer Genome Atlas(TCGA)were cross-referenced with UBE2S interacting proteins by survival package of R software;the key proteins were extracted through LASSO regression analysis to build the UIPM;the prognostic model risk scoring formula was established.The HCC patients in TCGA were divided into high risk group and low risk group based on median value of the risk scores.The predictive accuracy of UIPM was evaluated by receiver operating characteristic curve(ROC),and the predictive accuracy was further validated by International Cancer Genome Consortium(ICGC)Database;univariate regression analysis and multivariate Cox regression analysis were used to detect whether the UIPM risk score was an independent prognostic factor for HCC.Furthermore,the nomogram model was built.Results:A total of 97 UBE2S interacting proteins were identified through Co-IP combined with LC-MS analysis.The GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the interacting proteins were closely associated with cysteine-type endopeptidase activity,oxidative stress,and cell death.The TCGA revealed 5 163 HCC prognosis-related proteins;after intersecting with UBE2S interacting proteins,40 prognosis-related interacting proteins were found.Seven key proteins were determined through LASSO regression analysis,including UBE2S,heat shock protein family A member 8(HSPA8),heterogeneous nuclear ribonucleoprotein H1(HNRNPH1),chaperonin containing TCP1 subunit 3(CCT3),eukaryotic translation initiation factor 2 subunit 1(EIF2S1),receptor for activated C kinase 1(RACK1),and actin related protein 2/3 complex subunit 4(ARPC4),and the UIPM was constructed.There was significant difference in survival rate of the patients between high risk group and low risk group(P<0.05).The ROC curve analysis results showed the area under ROC curve(AUC)values of UIPM for predicting 1-year,2-year,and 3-year survival risk scores of the HCC patients were all greater than 0.7,indicating the model had high predictive accuracy.This was also confirmed by ICGC Database data.The univariate and multivariate Cox regression analysis results showed that the UIPM risk score was an independent prognostic risk factor for the HCC patients(P<0.05).The nomogram results showed good consistency between predicted survival rate and actual survival rate of the patient.Conclusion:A total of 97 interacting proteins that interact with UBE2S may promote the occurence and devolopment of HCC through oxidative stress and dysregulation of ferroptosis pathways.The UIPM risk score is an independent risk factor for the prognosis of HCC and can be used to predict the outcomes of the patients.UBE2S,HSPA8,HNRNPH1,CCT3,EIF2S1,RACK1,and ARPC4 could be regarded as the new biomarkers and therapeutic targets for HCC.

BACKGROUND:Although traditional therapies,including drugs and surgery,cannot repair the damaged myocardial tissue,the mortality rate of myocardial infarction remains high.Stem cells provide the possibility to solve this problem due to their self-renewal and multi-directional differentiation potential. OBJECTIVE:To analyze the research progress of stem cell therapy for myocardial infarction in recent ten years by bibliometric analysis. METHODS:The related articles on stem cells and myocardial infarction published in SCI-E and SSCI from January 1,2012 to December 1,2022 in the Web of Science database were searched.EXCEL,CiteSpace and VOSviewer software were used to make statistical and visualization analyses of the data such as the number of publications,authors,institutions,journals,countries and keywords. RESULTS AND CONCLUSION:A total of 3 210 core articles were published,and the total number increased year by year.hausenloy,derek j.is the author with the largest number of publications,China is the country with the largest number of publications,and the Fourth Military Medical University is the institution with the largest number of publications.The research hotspots in this field are changing from cell experiments and animal experiments to clinical trials.In the past ten years,research in this field has been highly popular and still has great development prospects.It is necessary to promote international and inter-agency exchange and learning,and further explore the role of stem cells in the treatment of myocardial infarction.