BACKGROUND:Stress-induced damage to hippocampal neurons may underlie abnormalities in neuronal structure and function,ultimately leading to mood disorders.G protein-coupled receptors in brain tissue play an important role in mood regulation.OBJECTIVE:To analyze the mechanism of depression-like behavior in chronic social defeat stress mice based on high-throughput sequencing and bioinformatics analysis.METHODS:C57BL/6J mice were randomly divided into control group and model group.There was no special treatment in the control group,while a mouse model of chronic social defeat stress was established in the model group.Depression-like behavior was assessed through the sucrose preference test,tail suspension test,and forced swim test.Anxiety behavior was evaluated using the elevated plus-maze,while social behavior was measured through the social interaction test.Cognitive function was assessed with the Y-maze spontaneous alternation test.Immunofluorescence staining was performed to quantify microglia markers in the mouse hippocampus,and Nissl staining was used to examine neuronal damage in mice.High-throughput sequencing was used to identify differentially expressed genes and gene enrichment in the mouse hippocampus,and qPCR was used to measure the expression of G protein-coupled receptors in the mouse hippocampus.RESULTS AND CONCLUSION:(1)Compared with the control group,chronic social defeat stress mice showed significant behavioral impairments,including increased anxiety,depression,and cognitive deficits.(2)Additionally,the Nissl body light density in hippocampal neurons was significantly reduced in chronic social defeat stress mice.(3)Sequencing results revealed synaptic damage in the neurons after chronic social defeat stress.Microglia activation was also markedly increased in the hippocampus of CSDS mice.Furthermore,the expression of G protein-coupled receptors in the hippocampus was significantly higher in chronic social defeat stress mice compared with the control group.These findings suggest that chronic social defeat stress induces anxiety,depression,and cognitive deficits in mice,accompanied by neuropathological changes in the hippocampus,and that altered G protein-coupled receptors expression may play a key role in these behavioral and neuropathological changes.

Objective To explore the risk prediction model of major adverse cardiovascular events (MACE) in community patients with hypertension based on remote ambulatory blood pressure parameters. Methods From November 2023 to October 2024, 486 community patients with hypertension who received standardized management in Nanjing Medical University Affiliated to Suzhou Hospital were retrospectively selected. All patients wore remote ambulatory blood pressure monitor to obtain 24-hour ambulatory blood pressure data. Clinical data were collected and remote ambulatory blood pressure parameters [24-hour systolic blood pressure variability (SBPV), 24-hour diastolic blood pressure variability (DBPV), nighttime SBPV, nighttime DBPV, daytime SBPV, daytime DBPV] were extracted. The patients were followed up for 12 months, and were classified into MACE group (n=42) and non-MACE group (n=444) according to whether MACE occurred during follow-up. Multivariate Logistic regression analysis was adopted to screen the influencing factors for MACE. Based on the above factors, a risk prediction model was constructed and verified by receiver operating characteristic (ROC) curve. Results MACE occurred in 42 cases among 486 patients, with an incidence rate of 8.64%. Multivariate Logistic regression analysis suggested that nighttime DBPV (OR=1.119, 95%CI: 1.030-1.214), 24h-SBPV (OR=1.115, 95%CI: 1.007-1.235), nighttime SBPV (OR=1.116, 95%CI: 1.016-1.226) and diabetes mellitus (OR=2.762, 95%CI: 1.059-7.203) were independent factors for MACE (P<0.05). The model validation results revealed that the area under the ROC curve was 0.905 (95%CI: 0.854-0.956 ), and the model had a good discrimination degree. Conclusion Nighttime DBPV, 24h-SBPV, nighttime SBPV and diabetes mellitus are independent risk factors for MACE in community patients with hypertension. The clinical prediction model based on these variables exhibits certain predictive value on MACE risk.

Objective To investigate the prevalence of cognitive frailty and its associated factors among middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD) in Gusu District, Suzhou City, to provide a basis for intervention measures. Methods COPD patients managed at Pingjiang New Town Community Health Service Center in Gusu District from January to December 2024 were selected. Data were collected using the Fried Frailty Phenotype, Mini-Mental State Examination, and a general information questionnaire. Chi-square tests, one-way analysis of variance, and multivariate Logistic regression were used for data analysis. Results A total of 1 388 patients were included, with 916 males (65.99%) and 472 females (34.01%). Cognitive frailty was observed in 554 cases (prevalence: 39.91%). Univariate analysis showed significant differences in gender, education, visual impairment, hearing impairment, sleep disorders, and disease duration between the cognitive frailty and non-cognitive frailty groups (all P<0.05). Multivariate Logistic regression indicated that education was negatively associated with cognitive frailty (illiteracy OR=6.969, P<0.001; primary school OR=1.499, P=0.005), while visual impairment (OR=2.347, P<0.001), hearing impairment (OR=1.705, P<0.001), sleep disorders (OR=2.488, P<0.001), and disease duration (≤5 years OR=0.329, P<0.001; 6-10 years OR=0.487, P<0.001) were positively associated with cognitive frailty. Conclusion The prevalence of cognitive frailty among middle-aged and elderly COPD patients in Gusu District, Suzhou City, is high (39.91%). Epositively associated with cognitive frailtyducation, sensory impairments, sleep disorders, and disease duration are associated factors. Clinical attention to high-risk groups and implementation of early screening and targeted interventions are recommended.

ObjectiveTo investigate the effect of bone morphogenetic protein 3 （BMP3） on the expression of inflammatory factors and joint damage in adjuvant arthritis （AA） induced by Freund′s complete adjuvant （FCA） in rats. MethodsThe AIA model was established in SD rats by intradermal injection of FCA into the toes of the left hind limb， and BMP3 overexpressing adenovirus （Ad-BMP3） or control adenovirus （Ad-NC） was injected in situ into the knee joint cavity on day 8 after modeling. Subsequently， HE staining was used to observe the histopathological changes in the synovium， immunohistochemistry was used to detect the expression of BMP3 in the synovium， and ELISA was used to analyze the expression levels of IL-6， IL-1β and TNF-α in the serum. Primary fibroblast-like synoviocytes （FLS） were isolated from AIA rats， the expression of BMP3 in FLS was knocked down or overexpressed， and Western blot and qRT-PCR were used to detect the expression levels of BMP3 and inflammatory factors in FLS. ResultsHE staining confirmed the successful establishment of the AIA model. Compared with normal rats， AIA rats showed decreased BMP3 expression in synovial tissue. Knockdown of BMP3 promoted the protein expression of inflammatory factors （IL-6， IL-1β， IL-17A， TNF-α） and the mRNA expression of chemokines ［C-C motif chemokine ligand 2 （CCL2）， C-C motif chemokine ligand 3 （CCL3）， Vascular Cell Adhesion Molecule-1 （VCAM-1）］ in FLS. In contrast， overexpression of BMP3 suppressed the expression of these inflammatory factors and chemokines. Intra-articular injection of BMP3-overexpressing adenovirus in AIA rats upregulated BMP3 expression in synovial tissue and inhibited synovial inflammation and bone erosion. ConclusionBMP3 suppresses the production of inflammatory factors and chemokines in FLS， thereby alleviating synovial hyperplasia and bone erosion in arthritis.

Cardiovascular diseases （CVD）， particularly atherosclerosis， represent a major global health burden. Recent studies have revealed that innate immune cells such as monocytes and macrophages can develop immune memory after an initial stimulus， a phenomenon termed “trained immunity”. Growing evidence indicates that trained immunity serves as an underlying mechanism of chronic inflammation in atherosclerotic cardiovascular diseases. This review focuses on outlining the key effector cells involved in trained immunity and their mechanisms of formation， including processes such as metabolic reprogramming and epigenetic modifications， which collectively lead to a heightened immune response upon secondary stimulation. Furthermore， this review systematically summarizes the role of trained immunity in the initiation and progression of atherosclerosis， and elaborates on various therapeutic strategies targeting trained immunity along with their application prospects.

BACKGROUND:Stress-induced damage to hippocampal neurons may underlie abnormalities in neuronal structure and function,ultimately leading to mood disorders.G protein-coupled receptors in brain tissue play an important role in mood regulation.OBJECTIVE:To analyze the mechanism of depression-like behavior in chronic social defeat stress mice based on high-throughput sequencing and bioinformatics analysis.METHODS:C57BL/6J mice were randomly divided into control group and model group.There was no special treatment in the control group,while a mouse model of chronic social defeat stress was established in the model group.Depression-like behavior was assessed through the sucrose preference test,tail suspension test,and forced swim test.Anxiety behavior was evaluated using the elevated plus-maze,while social behavior was measured through the social interaction test.Cognitive function was assessed with the Y-maze spontaneous alternation test.Immunofluorescence staining was performed to quantify microglia markers in the mouse hippocampus,and Nissl staining was used to examine neuronal damage in mice.High-throughput sequencing was used to identify differentially expressed genes and gene enrichment in the mouse hippocampus,and qPCR was used to measure the expression of G protein-coupled receptors in the mouse hippocampus.RESULTS AND CONCLUSION:(1)Compared with the control group,chronic social defeat stress mice showed significant behavioral impairments,including increased anxiety,depression,and cognitive deficits.(2)Additionally,the Nissl body light density in hippocampal neurons was significantly reduced in chronic social defeat stress mice.(3)Sequencing results revealed synaptic damage in the neurons after chronic social defeat stress.Microglia activation was also markedly increased in the hippocampus of CSDS mice.Furthermore,the expression of G protein-coupled receptors in the hippocampus was significantly higher in chronic social defeat stress mice compared with the control group.These findings suggest that chronic social defeat stress induces anxiety,depression,and cognitive deficits in mice,accompanied by neuropathological changes in the hippocampus,and that altered G protein-coupled receptors expression may play a key role in these behavioral and neuropathological changes.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Purpose: This study aimed to develop and evaluate the effectiveness of the Trauma-nursing Education and Skill Support (TESS) program based on the ADDIE model (Analysis, Design, Development, Implementation, Evaluation model). The program was designed to enhance trauma nurses’ clinical competencies, including trauma-related knowledge, self-efficacy, and problem-solving ability, through the integration of theoretical education and simulation-based practice. Methods: A quasi-experimental study using a non-equivalent control group pretest–posttest design was conducted. Participants included 108 trauma nurses from regional trauma centers, military trauma centers, and emergency care facilities, who were assigned to an experimental group (n=52) or a control group (n=56). The TESS program consisted of a 2-day, 14-hour blended-learning course that included eight lecture sessions and four simulation-based practice stations. Data were collected at baseline, immediately after the intervention, and at 6 months using validated instruments measuring trauma-related knowledge, self-efficacy, and problem-solving ability. Two-way repeated-measures analysis of variance was used for data analysis. Results: The experimental group demonstrated significant improvements in trauma-related knowledge, self-efficacy, and problem-solving ability compared with baseline (all p<.001). These improvements were sustained at 6 months, although trauma-related knowledge scores showed a slight decline compared with immediate posttest levels. Between-group analyses confirmed significant group-by-time interaction effects for all outcomes: trauma-related knowledge (η2=0.12, p<.001), self-efficacy (η2=0.09, p=.002), and problem-solving ability (η2=0.08, p=.003). Conclusion The TESS program effectively enhanced trauma nurses’ trauma-related knowledge, self-efficacy, and problem-solving ability, with effects sustained for up to 6 months. Incorporating blended learning and simulation-based training into standardized trauma nursing education may strengthen clinical competencies and ultimately contribute to improved patient outcomes.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Objectives: This study, part of the ongoing Korean National Burden of Disease (KNBD) updates, assesses disability-adjusted life years (DALYs) and disability-adjusted life expectancy (DALE) in Korea, taking into account the effects of coronavirus disease 2019 and emphasizing the importance of analyzing these metrics jointly. Methods: Data were obtained from Statistics Korea, the National Health Insurance Service, and the Korea Disease Control and Prevention Agency. DALYs and DALE were calculated using an incidence-based approach, following disease classification, disability weights, and estimation procedures consistent with prior KNBD research. Results: Compared with earlier estimates, DALYs showed a slight decline in 2020 followed by an increase in 2021, with this pattern observed across all income quintiles. For DALE, both men and women experienced modest gains relative to earlier studies; however, a decrease occurred across all income levels in 2021 compared with 2020. Regional disparities in DALE also narrowed beginning in 2020, with a more marked reduction among women. Conclusions Unlike previous studies, this research presents DALYs and DALE concurrently, offering a more comprehensive perspective on summary measures of population health. The post-2020 rise in DALYs underscores the growing need for effective chronic disease management. Additionally, widening income-based disparities in DALE highlight the urgency of addressing health inequities. Continued monitoring and updates of DALYs and DALE are necessary to understand and respond to these evolving trends.