Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To explore the use of T2-fluid attenuated inversion recovery(FLAIR)sequences with a shorter TR to significantly reduce examination time without compromising diagnostic accuracy and image quality,and to obtain satisfactory brain gray and white matter contrast images via adjusting the TE.Methods A total of 60 patients underwent brain MR were selected,and each patient was scanned using two different T2-FLAIR sequences.The scan parameters for sequence A group were TR 9 000 ms,inversion time(TI)2 500 ms,and TE 120 ms.For sequence B group,the scan parameters were TR 6 000 ms,TI 2 000 ms,and TE 120-200 ms(with 20 ms intervals),respectively,and all images data were labeled as B1 to B5.A double-blind method was used to observe the images from both groups,with a 5-point rating scale.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)of brain gray and white matter,and the contrast of brain gray and white matter were measured,respectively.SPSS 26.0 statistical software was used for subjective and objective evaluations of the images from both groups.Results For subjective evaluation,there were statistically significant differences in image quality with TE ranged from 120 to 200 ms in B group(H=41.4,P＜0.05).In pairwise comparisons,images from B3 group(TE 160 ms)showed no statistically significant difference compared to A group in subjective evaluations by two physicians(P＞0.05).For objective evaluation,A group exhibited significantly higher SNR compared to B group.Among the images in B group with TE ranged from 120 to 200 ms,SNR decreased gradually with increased TE,while CNR and contrast increased progressively(P＜0.05).Specifically,there were no statistically significant differences between B3 and A groups in terms of CNR and contrast(P＞0.05).Conclusion T2-FLAIR sequences with a shorter TR can significantly reduce examination time.By adjusting the TE,satisfactory brain gray and white matter contrast images can be obtained.When TE is 160 ms,the contrast of brain gray and white matter is optimal,and the SNR of the images meets the requirements for clinical diagnosis.

Immune checkpoint inhibitors(ICIs)are currently used to treat a variety of tumors.However,there are adverse reactions related to the immune system.Type 1 diabetes mellitus(T1DM)outbreak is a rare endocrine complication,as is ICIs-related myocarditis.This article reports a patient with diabetic ketoacidosis and severe myocarditis after ICIs treatment for lung cancer.After fluid infusion,acid correction,insulin hypoglycemic therapy,and high-dose hormone pulse therapy,the patient showed clinical improvement and was discharged.Through the analysis of the patient's clinical data,we aimed to improve clinicians'understanding of ICIs-associated DM and myocarditis,and to review the literature on possible pathogenesis and treatment.

Objective To investigate the effect of miR-29b-3p targeting insulin-like growth factor-1(IGF-1)on high glucose-induced injury in human retinal microvascular endothelial cells(HRMECs)and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods HRMECs were di-vided into the following groups:control group(normal culture),high glucose(HG)group(treated with 30.0 mmol·L-1 glucose for 48 h),inhibitor-NC group,miR-29b-3p inhibitor group,miR-29b-3p inhibitor+si-NC group,miR-29b-3p inhib-itor+si-IGF-1 group(all transfected with corresponding plasmids for 24 h after HG treatment),and LY294002 group(treated with 40 μmol·L-1 LY294002 for 24 h).The expression level of miR-29b-3p was detected by quantitative real-time PCR(qRT-PCR).Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Intracellular reactive oxygen species(ROS)levels were measured by immunofluorescence.The expression levels of malondialdehyde(MDA),superox-ide dismutase(SOD),and glutathione peroxidase(GSH-Px)were determined using enzyme-linked immunosorbent assay(ELISA).Cell apoptosis was analyzed by flow cytometry.Autophagosome formation was observed under a transmission electron microscope.The protein expression levels related to apoptosis,autophagy,IGF-1,and the PI3K/Akt/mTOR path-way were examined by Western blot.The targeting relationship between miR-29b-3p and IGF-1 was verified by a dual-lucif-erase reporter assay.Results Compared with the Control group,the HG group showed significant increases in the ex-pression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the in-hibitor-NC group,the miR-29b-3p inhibitor group exhibited significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the num-ber of autophagosomes were significantly increased(all P＜0.05).Compared with the miR-29b-3p inhibitor+si-NC group,the miR-29b-3p inhibitor+si-IGF-1 group demonstrated significant increases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the HG group,the LY294002 group showed significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly increased(all P＜0.05).The dual-luciferase activity was significantly lower in cells co-transfected with IGF-1-WT and miR-29b-3p mimic compared to miR-NC cells(P＜0.05).Conclusion Inhibition of miR-29b-3p can target upregulation of IGF-1 expression levels,thereby inhibiting the PI3K/Akt/mTOR pathway and improving high glucose induced cell damage in HRMECs.

How to use family doctors as a starting point to improve the level of chronic disease management is still a ma-jor challenge in China.This study summarizes the current chronic disease management models,family doctor contract service models,and new digital health technologies in China.It expounds the connection between the three and explores the advantages of new digital health technologies in chronic disease management and family doctor contract services,aiming to provide a solid theoretical foundation for improving the level of chronic disease management.

Objective:To explore the impact and underlying mechanisms of social support on illness uncertainty among parents of children with autism.Methods:A convenience sample of 312 parents of children with autism was recruited from the outpatient clinic of Peking University Sixth Hospital between September 2023 and January 2024. Data were collected using a general information questionnaire, the Chinese version of the Parent's Perception Uncertainty Scale (PPUS), the Social Support Scale for Families with Children with Autism, the Generalized Anxiety Disorder-7 (GAD-7), and the Questionnaire on Caregiving Issues and Service Needs of Parents of Children with Autism. Independent samples t-tests or one-way ANOVA were used to compare illness uncertainty scores across different characteristics. Pearson correlation analysis examined relationships among illness uncertainty, social support, caregiving issues and service needs, and anxiety. Chain mediation analysis was conducted using the SPSS macro PROCESS v4.1 to test the mediating roles of caregiving issues and service needs and anxiety. Results:The illness uncertainty score of the 307 valid respondents was (82.40±14.09). Mediation analysis indicated a direct effect of social support on illness uncertainty (effect value=-1.040), accounting for 72.27% of the total effect (-1.040/-1.439). A chain-mediated effect through caregiving issues and service needs and anxiety was also observed (effect value=-0.065), accounting for 4.50% of the total effect (-0.065/-1.439) .Conclusions:Parents of children with autism experience a relatively high level of illness uncertainty. Enhancing social support, addressing caregiving issues and service needs, alleviating parental anxiety may reduce their illness uncertainty.

Immune checkpoint inhibitors(ICIs)are currently used to treat a variety of tumors.However,there are adverse reactions related to the immune system.Type 1 diabetes mellitus(T1DM)outbreak is a rare endocrine complication,as is ICIs-related myocarditis.This article reports a patient with diabetic ketoacidosis and severe myocarditis after ICIs treatment for lung cancer.After fluid infusion,acid correction,insulin hypoglycemic therapy,and high-dose hormone pulse therapy,the patient showed clinical improvement and was discharged.Through the analysis of the patient's clinical data,we aimed to improve clinicians'understanding of ICIs-associated DM and myocarditis,and to review the literature on possible pathogenesis and treatment.

Objective To investigate the effect of miR-29b-3p targeting insulin-like growth factor-1(IGF-1)on high glucose-induced injury in human retinal microvascular endothelial cells(HRMECs)and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods HRMECs were di-vided into the following groups:control group(normal culture),high glucose(HG)group(treated with 30.0 mmol·L-1 glucose for 48 h),inhibitor-NC group,miR-29b-3p inhibitor group,miR-29b-3p inhibitor+si-NC group,miR-29b-3p inhib-itor+si-IGF-1 group(all transfected with corresponding plasmids for 24 h after HG treatment),and LY294002 group(treated with 40 μmol·L-1 LY294002 for 24 h).The expression level of miR-29b-3p was detected by quantitative real-time PCR(qRT-PCR).Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Intracellular reactive oxygen species(ROS)levels were measured by immunofluorescence.The expression levels of malondialdehyde(MDA),superox-ide dismutase(SOD),and glutathione peroxidase(GSH-Px)were determined using enzyme-linked immunosorbent assay(ELISA).Cell apoptosis was analyzed by flow cytometry.Autophagosome formation was observed under a transmission electron microscope.The protein expression levels related to apoptosis,autophagy,IGF-1,and the PI3K/Akt/mTOR path-way were examined by Western blot.The targeting relationship between miR-29b-3p and IGF-1 was verified by a dual-lucif-erase reporter assay.Results Compared with the Control group,the HG group showed significant increases in the ex-pression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the in-hibitor-NC group,the miR-29b-3p inhibitor group exhibited significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the num-ber of autophagosomes were significantly increased(all P＜0.05).Compared with the miR-29b-3p inhibitor+si-NC group,the miR-29b-3p inhibitor+si-IGF-1 group demonstrated significant increases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;whereas the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly decreased(all P＜0.05).Compared with the HG group,the LY294002 group showed significant decreases in the expression levels of miR-29b-3p,ROS,MDA,Bax,Cleaved-caspase 3,p62,the p-PI3K/PI3K ratio,the p-Akt/Akt ratio,the p-mTOR/mTOR ratio,and the cell apoptosis rate;while the expression levels of IGF-1,SOD,GSH-Px,the LC3Ⅱ/LC3Ⅰ ratio,cell viability,and the number of autophagosomes were significantly increased(all P＜0.05).The dual-luciferase activity was significantly lower in cells co-transfected with IGF-1-WT and miR-29b-3p mimic compared to miR-NC cells(P＜0.05).Conclusion Inhibition of miR-29b-3p can target upregulation of IGF-1 expression levels,thereby inhibiting the PI3K/Akt/mTOR pathway and improving high glucose induced cell damage in HRMECs.

How to use family doctors as a starting point to improve the level of chronic disease management is still a ma-jor challenge in China.This study summarizes the current chronic disease management models,family doctor contract service models,and new digital health technologies in China.It expounds the connection between the three and explores the advantages of new digital health technologies in chronic disease management and family doctor contract services,aiming to provide a solid theoretical foundation for improving the level of chronic disease management.

OBJECTIVE To investigate the improvement effect and mechanism of desloratadine citrate disodium in mice with hypersensitivity pneumonitis(HP).METHODS Sixty mice were randomly divided into blank control group(normal saline),model group(normal saline),prednisone group(positive control,20 mg/kg)and desloratadine citrate disodium low-,medium-and high-dose groups(0.5,1,2 mg/kg),with 10 mice in each group.Except for the blank control group,mice in other groups were intraperitoneally injected with ovalbumin(OVA)and exposed to OVA inhalation to establish the HP model.On day 22 post-modeling,mice in each group were administered the corresponding drugs or normal saline,once a day,for 11 consecutive days.After the last administration,lung function and airway hyperreactivity were assessed.The levels of interleukin-1β(IL-1β),IL-4 and IL-6 in serum as well as the levels of IL-8,IL-13 and IL-17A in bronchoalveolar lavage fluid were determined.Pathological changes in lung tissue of mice were evaluated using Masson staining.Furthermore,the expressions of fibrosis-related proteins,including transforming growth factor β1(TGF-β1),type Ⅲ collagen(Col-Ⅲ)and fibronectin(FN)were determined in lung tissues.RESULTS Compared with the blank control group,the model group showed significant deterioration in lung function(P＜0.01),while airway resistance and serum levels of IL-1β,IL-4,IL-6 and the levels of IL-8,IL-13 and IL-17A in the bronchoalveolar lavage fluid were increased significantly(P＜0.01).The lung tissues exhibited alveolar collapse,atrophy,and structural disarray,along with the formation of extensive deposits of blue collagen fibers,the percentage of positive staining increased significantly(P＜0.01).Additionally,the expression levels of TGF-β1,Col-Ⅲ,and FN proteins in the lung tissues were also increased significantly(P＜0.01).After intervention with desloratadine citrate disodium,the pathological changes in the lung tissues of mice in each dosage group of desloratadine citrate disodium showed varying degrees of improvement,and most of the aforementioned indicator levels were significantly reversed(P＜0.05 or P＜0.01).CONCLUSIONS Desloratadine citrate disodium can improve the lung function and airway hyperreactivity of HP mice,inhibit the release of inflammatory factors in serum and bronchoalveolar lavage fluid,and reduce the deposition of collagen fibers.Its mechanism of action may be related to anti-inflammatory,immunomodulatory,and antifibrotic effects.