Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region （3’UTR） of slit guidance ligand 1 （Slit1） （Slit1-3’UTR） on the fibrotic phenotypes of cardiac fibroblasts （CFs） and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs （mCFs）. The expression of fibrosis-related genes in mCFs， such as collagen type 1 alpha1（COL1A1）， collagen type 3 alpha3 （COL3A1） and alpha smooth muscle actin （α-SMA） were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ （Ang Ⅱ） was used to treat mCFs， and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt， miR-34a-5p mimic was transfected into mCFs， followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt， and the levels of miR-34a-5p and its target gene SIRT1（si-SIRT1） in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes， proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs， while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes， and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.

[Objective]To investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A(IDH3A)on cardiomyocyte hypertrophy.[Methods]The expression of IDH3A in the myocardium of healthy volunteers(n=10)and patients with heart failure(HF)(n=10),and in the myocardium of mice subjected to transverse aortic constriction(TAC)surgery and sham operation,as well as in phenylephrine(PE)-induced neonatal rat ventricular cardiomyocytes(NRVCs),was assessed by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot assay.The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated.The effect of IDH3A on NRVCs area was examined by phalloidin staining assay.A mutant of IDH3A with abolished enzymatic activity,IDH3A_D208A,was generated through site-directed mutagenesis.The impact of this IDH3A mutant on the hypertrophic phenotype,ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity.The effect of exogenous α-ketoglutaric acid(AKG)on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay,respectively.[Results]IDH3A was significantly decreased in the myocardium of HF patients,in the myocardium of TAC-operated mice,and in PE-induced NRVCs(P=0.005 2,P=0.026 6,P=0.041 3 and P=0.006 6,respectively).Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs(P<0.000 1,P=0.000 1 and P=0.000 2,respectively).The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs(P=0.001 2 and P<0.000 1,respectively),whereas the enzymatically inactive IDH3A mutant lacked this effect.Exogenous AKG provision could,but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy.[Conclusion]IDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level,providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

Objective:To explore the application effect of high-fidelity intelligent simulator combined with scenario simulation for emergency response training in the Department of Radiology, and to improve the emergency preparedness of medical, nursing, and technical staff in managing contrast agent adverse reactions.Methods:From January to July 2024, 132 medical, nursing, and technical staff from the Department of Radiology of a tertiary hospital in Chengdu City, China were selected as the training subjects. The high-fidelity intelligent simulator combined with scenario simulation teaching mode was used to conduct emergency response training for the participants. The differences in theoretical knowledge and post competence regarding contrast agent adverse reactions among the staff were compared before and after the training. A self-made questionnaire was used to investigate their needs and satisfaction of the emergency response training. SPSS 26.0 was used for data analysis. The differences in theoretical knowledge and post competence scores before and after training were compared using the paired samples t test. Results:After the training, the average score of theoretical knowledge examination increased from (84.32±10.19) points to (90.34±7.87) points, and the difference was statistically significant ( P<0.001). After the training, the scores of knowledge reserve, operational skills, situational decision-making ability, professional literacy, comprehensive literacy, and overall post competency were all significantly higher than those before the training ( P<0.05). The satisfaction score of emergency response training was (4.17±0.25) points. Conclusions:High-fidelity intelligent simulator combined with scenario simulation training improved the emergency preparedness and teamwork of radiology staff in clinical emergencies. The training received high recognition and satisfaction from the participants, which is of great significance for clinical emergency response and patient safety.

Objective To investigate the effect of Jiawei Simiao powder on the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway through miR-146a in monosodium urate(MSU)crystal-induced RAW264.7 macrophage inflammation models,and to explore its anti-inflammatory mechanism.Methods A cell model of gouty arthritis was established by inducing RAW264.7 cells with MSU crystals.Cells were divided into control,model,Jiawei Simiao powder,and colchicine groups and cell viability was assessed using the CCK-8 method.Levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.Expression levels of miR-146a miRNA and TLR4,myeloid differentiation factor 88(MyD88),TNF receptor-associated factor 6(TRAF6),and NF-κB p65 mRNA were detected by quantitative real-time polymerase chain reaction amplification technology,and protein expression levels of TLR4,MyD88,TRAF6,and phospho(p)-NF-κB p65 were evaluated by Western blot.Results miR-146a expression was significantly decreased in the model group compared with the control group(P＜0.01),while mRNA and protein expression levels of TLR4,MyD88,and TRAF6,and protein expression of p-NF-κB p65,IL-1β,IL-6,and TNF-α were significantly increased(P＜0.01).In contrast,miR-146a expression was significantly increased(P＜0.01)and mRNA and protein expression of TLR4,MyD88,and TRAF6,and p-NF-κB p65 protein expression(P＜0.01),as well as IL-1β,IL-6,and TNF-α levels(P＜0.05)were significantly decreased in the Jiawei Simiao powder and colchicine groups.Conclusions Jiawei Simiao powder may alleviate MSU crystal-induced macrophage inflammatory responses by upregulating miR-146a,suppressing TLR4/NF-κB signaling pathway activation,and decreasing secretion of inflammatory factors.

Objective:To understand the latent categories of apathy in young and middle-aged patients with hemorrhagic stroke and analyze the relationship between these categories and disability acceptance, providing a theoretical basis for targeted interventions.Methods:A convenience sampling method was used to select young and middle-aged patients with hemorrhagic stroke hospitalized at Huai′an First Hospital Affiliated to Nanjing Medical University between September 2020 and September 2023. A general information questionnaire, the Apathy Evaluation Scale-Clinician Administered, and the Acceptance of Disability Scale Revised were used for a cross-sectional survey. Latent profile analysis was conducted using Mplus 8.7 software to categorize apathy in these patients, and differences in disability acceptance among the categories were compared.Results:A total of 210 questionnaires were distributed and 203 valid questionnaires were collected. Among 203 patients were included, with 112 males and 91 females, aged 30-59 (47.60 ± 8.51) years old. The apathy score was (46.66 ± 8.78) points, and three latent categories were identified: "high active ability-low apathy" (26.1%, 53/203), "high social ability-moderate apathy" (28.6%, 58/203), and "generally high apathy" (45.3%, 92/203). The total disability acceptance scores for the three categories were (78.19 ± 13.30), (69.50 ± 11.01), and (60.86 ± 14.00) points, respectively, with statistically significant differences ( F=30.39, P<0.01). Conclusions:Apathy in young and middle-aged patients with hemorrhagic stroke can be categorized into three latent profiles, with differences in disability acceptance among the categories. Targeted management and interventions should be developed based on these homogeneous groups to improve disability acceptance.

Objective:To explore the application effect of high-fidelity intelligent simulator combined with scenario simulation for emergency response training in the Department of Radiology, and to improve the emergency preparedness of medical, nursing, and technical staff in managing contrast agent adverse reactions.Methods:From January to July 2024, 132 medical, nursing, and technical staff from the Department of Radiology of a tertiary hospital in Chengdu City, China were selected as the training subjects. The high-fidelity intelligent simulator combined with scenario simulation teaching mode was used to conduct emergency response training for the participants. The differences in theoretical knowledge and post competence regarding contrast agent adverse reactions among the staff were compared before and after the training. A self-made questionnaire was used to investigate their needs and satisfaction of the emergency response training. SPSS 26.0 was used for data analysis. The differences in theoretical knowledge and post competence scores before and after training were compared using the paired samples t test. Results:After the training, the average score of theoretical knowledge examination increased from (84.32±10.19) points to (90.34±7.87) points, and the difference was statistically significant ( P<0.001). After the training, the scores of knowledge reserve, operational skills, situational decision-making ability, professional literacy, comprehensive literacy, and overall post competency were all significantly higher than those before the training ( P<0.05). The satisfaction score of emergency response training was (4.17±0.25) points. Conclusions:High-fidelity intelligent simulator combined with scenario simulation training improved the emergency preparedness and teamwork of radiology staff in clinical emergencies. The training received high recognition and satisfaction from the participants, which is of great significance for clinical emergency response and patient safety.

Objective:To understand the latent categories of apathy in young and middle-aged patients with hemorrhagic stroke and analyze the relationship between these categories and disability acceptance, providing a theoretical basis for targeted interventions.Methods:A convenience sampling method was used to select young and middle-aged patients with hemorrhagic stroke hospitalized at Huai′an First Hospital Affiliated to Nanjing Medical University between September 2020 and September 2023. A general information questionnaire, the Apathy Evaluation Scale-Clinician Administered, and the Acceptance of Disability Scale Revised were used for a cross-sectional survey. Latent profile analysis was conducted using Mplus 8.7 software to categorize apathy in these patients, and differences in disability acceptance among the categories were compared.Results:A total of 210 questionnaires were distributed and 203 valid questionnaires were collected. Among 203 patients were included, with 112 males and 91 females, aged 30-59 (47.60 ± 8.51) years old. The apathy score was (46.66 ± 8.78) points, and three latent categories were identified: "high active ability-low apathy" (26.1%, 53/203), "high social ability-moderate apathy" (28.6%, 58/203), and "generally high apathy" (45.3%, 92/203). The total disability acceptance scores for the three categories were (78.19 ± 13.30), (69.50 ± 11.01), and (60.86 ± 14.00) points, respectively, with statistically significant differences ( F=30.39, P<0.01). Conclusions:Apathy in young and middle-aged patients with hemorrhagic stroke can be categorized into three latent profiles, with differences in disability acceptance among the categories. Targeted management and interventions should be developed based on these homogeneous groups to improve disability acceptance.

Objective To investigate the effect of Jiawei Simiao powder on the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway through miR-146a in monosodium urate(MSU)crystal-induced RAW264.7 macrophage inflammation models,and to explore its anti-inflammatory mechanism.Methods A cell model of gouty arthritis was established by inducing RAW264.7 cells with MSU crystals.Cells were divided into control,model,Jiawei Simiao powder,and colchicine groups and cell viability was assessed using the CCK-8 method.Levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.Expression levels of miR-146a miRNA and TLR4,myeloid differentiation factor 88(MyD88),TNF receptor-associated factor 6(TRAF6),and NF-κB p65 mRNA were detected by quantitative real-time polymerase chain reaction amplification technology,and protein expression levels of TLR4,MyD88,TRAF6,and phospho(p)-NF-κB p65 were evaluated by Western blot.Results miR-146a expression was significantly decreased in the model group compared with the control group(P＜0.01),while mRNA and protein expression levels of TLR4,MyD88,and TRAF6,and protein expression of p-NF-κB p65,IL-1β,IL-6,and TNF-α were significantly increased(P＜0.01).In contrast,miR-146a expression was significantly increased(P＜0.01)and mRNA and protein expression of TLR4,MyD88,and TRAF6,and p-NF-κB p65 protein expression(P＜0.01),as well as IL-1β,IL-6,and TNF-α levels(P＜0.05)were significantly decreased in the Jiawei Simiao powder and colchicine groups.Conclusions Jiawei Simiao powder may alleviate MSU crystal-induced macrophage inflammatory responses by upregulating miR-146a,suppressing TLR4/NF-κB signaling pathway activation,and decreasing secretion of inflammatory factors.