BackgroundNon-suicidal self-injury （NSSI） behavior among adolescents has become a global public health concern. Anxiety and depression are considered key factors influencing NSSI behavior， while social support may play a protective role in alleviating emotional and behavioral issues. However， existing research has primarily focused on the direct impact of individual factors on NSSI behavior， with insufficient exploration of the combined effects of anxiety， depression and social support. ObjectiveTo investigate the direct effect of anxiety on NSSI， the mediating role of depression and the moderating role of social support in relationship between anxiety and NSSI behavior， thus to provide references for the prevention and intervention of NSSI behavior among adolescents. MethodsIn February 2022， a total of 40 820 students in grades 7 to 12 across 10 middle schools in a district of Chengdu were selected as participants， and they were assessed using Generalized Anxiety Disorder Scale-7 item （GAD-7）， Patient's Health Questionnaire Depression Scale-9 item （PHQ-9）， Social Support Scale for Urban Students （SSSUS） and Adolescent Self-Harm Scale （ASHS）. Pearson correlation analysis was conducted to examine the correlations between scale scores among adolescents with NSSI behaviors. Mediation and moderation analyses were performed using Process 3.5 in SPSS， and the significance was tested with bootstrapping. The interaction was visualized by using simple slope analysis. ResultsAmong 34 534 （84.60%） valid respondents， 542 adolescents （1.57%） reported engaging in NSSI behavior. Significant differences in gender， GAD-7 scores， PHQ-9 scores， and SSSUS scores were observed between NSSI behavior group and non-NSSI group （χ²/t=62.889， 71.120， 94.365， -41.464， P<0.01）.Adolesents with NSSI showed positive correlations between GAD-7 scores and both ASHS and PHQ-9 scores （r=0.158， 0.166， P<0.01）. PHQ-9 scores were positively correlated with ASHS scores （r=0.364， P<0.01）， but negatively correlated with SSSUS scores （r=-0.290， P<0.01）. SSSUS scores were negatively correlated with ASHS scores （r=-0.247， P<0.01）. Depression partially mediated the relationship between anxiety and NSSI behavior， with an effect size of 0.544 （95% CI： 0.162~0.944）， accounting for 35.79% of the total effect. Social support moderated the relationship between depression and NSSI bahavior， with an effect value of -0.082 （95% CI： -0.135~-0.029）. ConclusionAnxiety not only directly influences NSSI bahavior among adolescents， also indirectly exacerbates it through depression， while social support mitigates the impact of depression on NSSI behavior. ［Funded by Youth Project of National Natural Science Foundation of China （number， 82401812）； Project of Health Commission of Sichuan Province （number， 24LCYJPT18）］

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective To analyze the caregiver presence needs and their influencing factors among hospitalized elderly non-surgical patients and provide a basis for formulating relevant policies.Methods A descriptive qualitative study method was adopted.Through purposive sampling,semi-structured interviews were conducted on elderly non-surgical patients and their families and medical staff in Peking Union Medical College Hospital from September to October 2023.MAXQDA 2020 and the 7-step phenomenological analysis method of Colaizzi were used to classify and code the interview contents and identify themes.Results The categories of caregiver presence needs of elderly non-surgical patients included basic living assistance needs,disease monitoring needs,psychological support needs,as well as the needs for family members to provide economic support and participate in treatment decision-making.The influencing factors included advanced age,frailty,the lack of self-care ability in patients with comorbidities,the susceptibility of patients to sudden situations during the disease exacerbation period,the increased risk of unexpected events in patients with psychological distress,and patients' concerns about social support and medical decision-making.Conclusion The caregiver presence needs of elderly non-surgical patients during hospitalization are high and influenced by multiple factors.
Humans ; Caregivers/psychology* ; Aged ; Hospitalization ; Social Support ; Male ; Qualitative Research ; Female

BackgroundThe distressingly high prevalence of depressive symptoms among adolescents exerts profound impacts on their physical and psychological development， urgently necessitating effective preventive interventions. Existing studies， however， have predominantly focused on isolated risk factors， neglecting to construct an integrated model that systematically disentangles the intricate relationships linking parenting styles， learning burnout， and childhood trauma to adolescent depressive symptoms. Moreover， the potential protective roles of social support and psychological resilience in this context remain insufficiently elucidated. ObjectiveTo construct a structural equation model encompassing multiple pathways to unravel the comprehensive mechanisms through which negative parenting styles， childhood trauma， learning burnout， psychological resilience， and social support collectively influence adolescent depressive symptoms， thereby providing evidence-based intervention strategies. MethodsA stratified sampling technique was utilized to recruit 5 865 students from 12 middle schools in Chengdu City， Sichuan Province from March to May 2022. Participants were assessed using the following validated instruments： the Short-form Egna Minnen av Barndoms Uppfostran （s-EMBU）， the Childhood Trauma Questionnaire-Short Form （CTQ-SF）， the Adolescent Student Burnout Inventory， the Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， the Social Support Rating Scale （SSRS），and the Connor-Davidson Resilience Scale （CD-RISC）. A partial least squares structural equation modeling （PLS-SEM） approach was employed to construct a predictive framework examining the complex network of pathways through which negative parenting styles， childhood trauma， learning burnout， psychological resilience，and social support collectively influence depressive symptoms in adolescents. ResultsThe PHQ-9 scores demonstrated significant positive correlations with the scores on s-EMBU overprotection subscale （r=0.272， P<0.01）， s-EMBU rejection subscale （r=0.368， P<0.01）， CTQ-SF （r=0.288， P<0.01） and Adolescent Student Burnout Inventory （r=0.587， P<0.01）. Conversely， significant negative correlations were observed between PHQ-9 scores and both SSRS （r=-0.532， P<0.01） and CD-RISC scores （r=-0.418， P<0.01）. Negative parenting styles （β=0.113， 95% CI： 0.087-0.138） and learning burnout （β=0.339， 95% CI： 0.315-0.364） emerged as significant positive predictors of depressive symptoms， with childhood trauma mediating the relationship between negative parenting styles and depressive symptoms （effect size=0.018， 95% CI： 0.013-0.024）. Social support servesed as a mediating pathway between negative parenting styles and depressive symptoms （β=0.080， 95% CI： 0.069-0.092）， as well as between negative parenting styles and childhood trauma （β=0.041， 95% CI： 0.032-0.050）. It also functioned as an intermediary pathway linking learning burnout to depressive symptoms （β=0.092， 95% CI： 0.081-0.104） and connecting learning burnout with childhood trauma （β=0.048， 95% CI： 0.037-0.058）. Additionally， psychological resilience serveed as a mediating pathway between negative parenting styles and depressive symptoms （β=0.004， 95% CI： 0.002-0.007）， between learning burnout and depressive symptoms （β=0.037， 95% CI： 0.023-0.052）， and between childhood trauma and depressive symptoms （β=0.003， 95% CI： 0.001-0.006）. ConclusionLearning burnout exerts a direct effect on adolescent depressive symptoms. Negative parenting styles influence depressive symptoms both directly and indirectly through childhood trauma. Furthermore， social support and psychological resilience serve as mediator linking negative parenting styles and learning burnout to depressive symptoms in adolescents. ［Funded by Science and Technology Project of the Health Commission of Sichuan Province （number， 24LCYJPT18）］

Objective:To discuss the differences in serum proline dehydrogenase(ProDH)levels among chronic heart failure(CHF)patients with different ejection fraction types,and to clarify the effect of ProDH levels on cardiac function.Methods:A retrospective analysis of clinical data of 118 CHF patients was conducted.These patients were divided into heart failure with reduced ejection fraction(HFrEF)group(n=39),heart failure with mid-range ejection fraction group(HFmrEF)(n=42),and heart failure with preserved ejection fraction(HFpEF)group(n=37).A total of 45 non-CHF patients hospitalized during the same period were collected as control group.The general data of all the subjects in various groups were collected,and the levels of biochemical indicators and cardiac structure indicators in serum of all the subjects were detected.Spearman correlation analysis and point-biserial correlation analysis were used to analyze the correlation between serum ProDH levels and various biochemical indicators;multivariate Logistic regression analysis was used to analyze the factors influencing HFrEF and HFmrEF.Results:Compared with control group,the usage rate of beta-blockers of the patients in HFpEF group was significantly increased(P<0.05);in HFmrEF group,the percentage of male patients,the usage rate of statins,and the usage rate of beta-blockers were all significantly increased(P<0.05);in HFrEF group,the age and systolic blood pressure(SBP)of the patients were significantly decreased(P<0.05),while the usage rates of statins and beta-blockers of the patients were significantly increased(P<0.05).Compared with HFpEF group,the age of the patients in HFmrEF group was significantly decreased(P<0.05),and the percentage of male patients and the usage rate of statins were significantly increased(P<0.05);the age of the patients in the HFrEF group was significantly decreased(P<0.05),and the usage rate of statins was significantly increased(P<0.05).Compared with HFmrEF group,the SBP of the patients in HFrEF group was significantly decreased(P<0.05).Compared with control group,the serum levels of low-density lipoprotein cholesterol(LDL-c)of the patients in HFpEF and HFmrEF groups were significantly decreased(P<0.05),while the levels of N-terminal pro-brain natriuretic peptide(NT-proBNP)were significantly increased(P<0.05);the serum levels of glomerular filtration rate(GFR)and ProDH of the patients in HFrEF group were significantly decreased(P<0.05),and the levels of fasting blood glucose(FBG)and NT-proBNP were significantly increased(P<0.05).Compared with HFpEF group,the serum hemoglobin(Hb)level of the patients in HFmrEF group was significantly increased(P<0.05);the serum NT-proBNP level of the patients in HFrEF group was significantly increased(P<0.05),while the ProDH level was significantly decreased(P<0.05).Compared with HFmrEF group,the serum NT-proBNP level of the patients in HFrEF group was significantly increased(P<0.05).Compared with control group,the left atrial diameter(LAD)and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity(E/Em)of the patients in HFpEF,HFmrEF,and HFrEF groups were significantly increased(P<0.05);the left ventricular end-diastolic diameter(LVEDD)of the patients in HFmrEF and HFrEF groups were significantly increased(P<0.05),and the left ventricular ejection fraction(LVEF)were significantly decreased(P<0.05).Compared with HFpEF group,the LVEDD of the patients in HFmrEF and HFrEF groups were significantly increased(P<0.05),and the LVEF were significantly decreased(P<0.05);the LAD of the patients In HFrEF group was significantly increased(P<0.05).Compared with HFmrEF group,the E/Em ratio of the patients in HFrEF group was significantly increased(P<0.05),and the LVEF was significantly decreased(P<0.05).The serum ProDH levels of the patients were negatively correlated with LVEDD(r=-0.210,P=0.007)and positively correlated with LVEF(r=0.220,P=0.005).Male and elevated FBG levels were the risk factors for cardiac function,while the increasing serum GFR and ProDH levels were the protective factors for cardiac function.Conclusion:There are differences in ProDH levels among the CHF patients with different ejection fraction types.The patients with poorer cardiac function have lower serum ProDH levels,and higher ProDH levels may be beneficial for improving the left ventricular systolic function in the CHF patients.

Objective To investigate the clinical efficacy of Yiqi Huayu Decoction(mainly composed of Astragali Radix,Dioscoreae Rhizoma,Poria,fried Euryales Semen,Ecliptae Herba,Rosae Laevigatae Fructus,charred Crataegi Fructus,Ligustri Lucidi Fructus,Salviae Miltiorrhizae Radix et Rhizoma,and Leonuri Herba)combined with Calcium Dobesilate in the treatment of diabetic nephropathy(DN)with qi deficiency and blood stasis syndrome,and to observe the effect of the therapy on vascular endothelial growth factor(VEGF)and insulin-like growth factor 1(IGF-1).Methods Ninety patients with DN of qi deficiency and blood stasis type were randomly divided into an observation group and a control group,with 45 patients in each group.All patients received basic hypoglycemic therapy and treatment for controlling blood pressure and regulating lipid metabolism disorders.Moreover,the patients in the control group were given Calcium Dobesilate orally,and the patients in the observation group were given Yiqi Huayu Decoction combined with Calcium Dobesilate.The course of treatment lasted for 3 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters and serum VEGF and IGF-1 levels in the two groups of patients were observed before and after the treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 3 months of treatment,the total effective rate of the observation group was 91.11%(41/45),and that of the control group was 75.56%(34/45).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.05).(2)After one month and 3 months of treatment,the TCM syndrome scores of both groups were significantly lower than those before treatment(P＜0.05),and the scores after 3 months of treatment in the two groups were significantly lower than those after one month of treatment(P＜0.05).The intergroup comparison showed that the reduction of TCM syndrome scores of the observation group was significantly superior to that of the control group after one month and 3 months of treatment(P＜0.01).(3)After treatment,the levels of renal function parameters such as serum creatinine(Scr),blood urea nitrogen(BUN),and glomerular filtration rate(GFR)in the two groups of patients were significantly improved compared with those before treatment(P＜0.05),and the observation group's effect on the improvement of all renal function parameters was significantly superior to that of the control group(P＜0.01).(4)After treatment,the serum VEGF and IGF-1 levels in the two groups of patients were significantly lower than those before treatment(P＜0.05),and the observation group's effect on the decrease of serum VEGF and IGF-1 levels was significantly superior to that of the control group(P＜0.01).(5)In the course of treatment,no significant adverse reactions occurred in the two groups of patients,with a high degree of safety.Conclusion Yiqi Huayu Decoction combined with Calcium Dobesilate exerts certain therapeutic effect in treating DN patients with qi deficiency and blood stasis syndrome.The combined therapy can effectively down-regulate the serum levels of VEGF and IGF-1,significantly improve the renal function,and alleviate the clinical symptoms of the patients,with a high degree of safety.