Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

OBJECTIVES: Depression is a common negative emotion that can significantly impact physical and mental health. Due to their occupational characteristics, medical staff are more susceptible to depression compared to the general population. This study aims to explore the influence of future-oriented coping on depression among medical staff and the mediating roles of psychological resilience and perceived stress, providing theoretical guidance for depression intervention strategies in this group. METHODS: A cross-sectional survey was conducted among medical staff at a tertiary hospital using convenience sampling. Data were collected via the "Wenjuanxing" platform. A total of 754 questionnaires were distributed; after excluding invalid responses (e.g., duplicate IPs or insufficient completion time), 655 valid questionnaires were retained (valid response rate: 86.87%). Instruments included a demographic questionnaire, the Future-Oriented Coping Scale, the Connor-Davidson Resilience Scale, the Perceived Stress Scale, and the Self-Rating Depression Scale. All scales demonstrated high internal consistency (Cronbach's α>0.88) and validity. SPSS 27.0 was used for descriptive analysis, and PROCESS macro (Model 6) was used to test the chain mediation model. Harman's one-factor test was applied to control for common method bias. RESULTS: Descriptive analyses showed that future-oriented coping was positively correlated with psychological resilience and negatively correlated with perceived stress and depression. Mediation analysis revealed that future-oriented coping significantly predicted lower depression levels among medical staff (β=-0.283, P<0.001). Psychological resilience partially mediated the relationship (effect size=-0.329, accounting for 34.13% of the total effect), as did perceived stress (effect size=-0.099, 10.27%). A significant chain mediation path was identified: "future-oriented coping → psychological resilience → perceived stress → depression" (effect size=-0.253, 26.24%). The total indirect effect accounted for 70.64% of the overall effect, highlighting the substantial role of the mediating pathways. CONCLUSIONS Future-oriented coping can reduce depressive symptoms in medical staff, with psychological resilience and perceived stress serving as key mediators in a chain structure. These findings suggest that enhancing future-oriented coping strategies and psychological resilience may improve stress adaptation and reduce depression levels in this population.
Humans ; Adaptation, Psychological ; Resilience, Psychological ; Cross-Sectional Studies ; Depression/psychology* ; Surveys and Questionnaires ; Stress, Psychological/psychology* ; Male ; Female ; Adult ; Middle Aged ; Medical Staff/psychology* ; Occupational Stress/psychology*

OBJECTIVES: Anxiety is a common negative emotion. Under current social circumstances, university young teachers face multiple stressors and are more prone to anxiety, seriously threatening their physical and mental health. This study aims to investigate the impact of job insecurity on anxiety of university young teachers, while exploring the mediating roles of perceived stress and insomnia on this relationship. METHODS: Using convenience sampling, young teachers from a general university in a Chinese province were surveyed online. Scores of the Job Insecurity Scale, Perceived Stress Scale, Athens Insomnia Scale-Short Form, and Generalized Anxiety Disorder Scale were collected. A chain mediation analysis was conducted using the PROCESS macro. RESULTS: A total of 798 subjects were finally included. The detection rate of anxiety among university young teachers was 36.47%. Mediation analysis showed that job insecurity not only had a direct effect on anxiety, but also indirectly affected anxiety via perceived stress (46.42% of the total effect) and insomnia (7.45%), as well as through the chain-mediating path of perceived stress→ insomnia (13.18%; all P<0.05). CONCLUSIONS Job insecurity is a significant predictor of anxiety in young university faculty. Perceived stress and insomnia serve as sequential mediators in this relationship. Targeted interventions addressing job insecurity, stress perception, and sleep disturbances, alongside efforts to improve mental health literacy and the working environment, may help promote the overall well-being of university young teachers.
Humans ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Universities ; Female ; Anxiety/psychology* ; Male ; Stress, Psychological/psychology* ; Adult ; Faculty/psychology* ; Surveys and Questionnaires ; China/epidemiology* ; Occupational Stress ; Job Security

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*