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Cognitive impairment and mood disturbances are increasingly linked to underlying mechanisms such as oxidative stress, neurotransmitter dysregulation, and reduced neurotrophic support. As conventional pharmacological treatments often provide limited efficacy or are associated with tolerability concerns, there is growing scientific interest in botanical supporting strategies that may modulate the above pathways and provide complementary support for cognitive function and emotional well-being. This study aimed to investigate the mechanistic basis of a botanical association consisting of a standardized Show less

Programmed cell death (PCD) has been linked to asthma, chronic obstructive pulmonary disease (COPD) and lung function, but the underlying genetic determinants remain unclear. A comprehensive multi-omics analysis was conducted by integrating genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data. To determine the causality between exposures and respiratory traits, Summary Data-Based Mendelian Randomization (SMR) and colocalization analyses were applied. External validation was performed using replication cohorts, along with transcriptome-wide association studies (TWAS), gene-based analysis, and tissue-specific analysis. Additionally, enrichment analysis was carried out to identify biological pathways linked to respiratory traits. To explore potential therapeutic targets, drug prediction and molecular docking analyses were employed to assess the pharmacological feasibility of candidate compounds. Through the integration of multi-omics analysis, we identified six PCD-related genes associated with respiratory traits. ERBB3, SFRP1, and FGFR1 demonstrated tier 1 evidence, linking them to COPD in never-smokers, forced expiratory volume in 1 second (FEV1), and FEV1/forced vital capacity (FVC), respectively. Additionally, HSPA1B and MAPK3 were classified as tier 2 genes, associated with non-allergic asthma risk and overall COPD risk, respectively. IDUA, categorized as a tier 3 gene, was related to overall asthma. These genes play critical roles in apoptotic signaling, mesenchymal development, and molecular binding processes, emphasizing their biological significance. Additionally, molecular docking demonstrated stable binding for candidate drugs and proteins encoded by identified genes. Our study offers critical insights into the genetic basis of asthma, COPD, and lung function by identifying six genes as potential biomarkers and therapeutic targets, contributing to the development of more effective interventions for these respiratory traits. Show less

Physical activity is essential for health and well-being during adolescence, and active behaviour early in life predicts higher physical activity levels in adulthood. Although adolescents with intellectual disability (ID) consistently show lower activity levels than peers without ID, national environments—such as school structures, disability support systems, and access to inclusive leisure activities—may influence these patterns. There is limited evidence from Sweden, a country with distinct educational and support frameworks for youth with ID. The present study aimed to examine physical activity patterns among Swedish adolescents with and without ID using accelerometer data. Physical activity was measured objectively using hip-worn accelerometers (ActiGraph GT3X) over seven consecutive days. This cross-sectional study included 45 adolescents with mild-to-moderate ID (median [IQR], 17.0 [14.0–19.0] years; 45.2% females) and 70 adolescents without ID (16.0 [15.0-16.3] years; 62.2% females). Physical activity was categorised as sedentary behaviour (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) and analysed across school days, weekend days, and separately for daytime and evening periods on school days. Overall, the relative amount of SB was similar between groups ( Adolescents with ID were generally less physically active than peers without ID, except during school-day daytime, where the MVPA was similar and LPA was higher. Leisure time, particularly weekends and school-day evenings, seems to be a critical period in achieving sufficient MVPA among adolescents with ID. Targeted interventions and coordinated support from key stakeholders such as school health services, paediatric health care, social care services and organised sports, with a particular focus on unstructured time, may help promote active lifestyles and reduce health disparities in this population. The online version contains supplementary material available at 10.1186/s12887-026-06679-9. Show less

Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. This study aimed to observe the mechanism of EA as an adjunct therapy to escitalopram oxalate (EO) on depressed patients. This study was designed as a single-blinded, double-dummy randomized controlled trial. 61 participants were diagnosed with mild-to-moderate depression according to the International Classification of Diseases 10th Edition (ICD-10, F32) were randomly allocated to receive EA + EO placebo, EO + sham EA, or EA + EO for six weeks treatment. The clinical assessment including depression severity, quality of life (QOL) and clinical safety. Biological indicators of immune-inflammation, the brain-derived neurotrophic factor and glucocorticoid inducible genes in peripheral blood of participants were measured by using enzyme linked immunosorbent assay and real-time polymerase chain reaction respectively before and after treatment. Three interventions improved the depression severity and QOL (P < 0.05), and no inter-group difference was found in the 6th week (P > 0.05). Anxiety psychic and somatic general symptoms in the EA + EO group were improved significantly than those of the other two groups (P < 0.05). After six-week treatment of EA + EO, blood SGK1 mRNA, GILZ mRNA, and BDNF levels were increased significantly ( Show less

Cerebrovascular diseases, including ischemic stroke and vascular cognitive impairment, represent a significant global health challenge due to the paucity of effective treatment options. Quercetin, a dietary flavonol, has emerged as a promising multi-target neuroprotective compound. This review elucidates the core mechanisms by which quercetin achieves vascular repair and neuroprotection in cerebrovascular diseases through synergistic regulation of multiple signaling pathways and explores strategies to bridge the gap between dietary intake and clinical application. At the vascular level, quercetin enhances antioxidant defense by activating the nuclear factor E2-related factor 2/heme oxygenase-1 axis, inhibits the Toll-like receptor 4/nuclear factor-κB pathway and NOD-like receptor protein 3 inflammasome, and maintains blood-brain barrier integrity by inhibiting matrix metalloproteinase-9 and upregulating tight junction proteins via the Wnt/ Show less

Peripheral nerve injury (PNI) is a significant health concern, affecting millions worldwide. Key neurotrophic factors, including nerve growth factor, brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor, have shown promise in facilitating neural regeneration. The effects of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids have been extensively studied, emphasizing the importance of appropriate timing and duration of administration. Antioxidants such as vitamin E and melatonin have exhibited neuroprotective effects in animal models, but further research is necessary to determine their efficacy, optimal dosage, and administration in humans. Immunosuppressive agents like tacrolimus (FK506) and cyclosporin A have demonstrated substantial potential in enhancing peripheral nerve recovery. Supportive strategies, including physical therapy and neuromodulation techniques such as electrical and transcranial stimulation, have shown effectiveness in promoting nerve regeneration. Advances in bioengineering, including nerve conduits and stem cell transplantation, which mimic natural nerve repair mechanisms, hold considerable promise for improving PNI treatments. In conclusion, PNI therapy is progressing towards an integrative approach, combining surgical techniques with pharmacological interventions, bioengineering, and regenerative medicine to enhance outcomes while minimizing adverse effects. This review explores recent advancements in peripheral nerve regeneration using both natural and synthetic agents, highlighting the shift toward more comprehensive treatment strategies. Show less

Swiss adolescents fall short of the WHO's guideline of 60 min of moderate-to-vigorous physical activity (MVPA) per day. Developing targeted interventions or policies requires an understanding of adolescents' daily activity patterns. Since adolescents spend much time at school, it is essential to consider not only leisure but also school segments when assessing physical activity (PA). Therefore, this study investigates how Swiss adolescents' PA is distributed across different school time segments and examines to what extent they meet recommended activity levels. This cross-sectional study uses baseline data from the Active School project. The sample included 666 7th-grade students (mean age = 13.27 ± 0.55 years, 47.7% boys, 51.8% girls, 0.5% diverse) from 12 secondary schools. PA data, gathered over five schooldays using wrist-worn GENEActiv accelerometers, were segmented into physical education (PE), recess, classroom time, entire school time, and leisure time. Activity levels were categorized into inactivity (IN), light physical activity (LPA), and MVPA. Descriptive and inferential statistics (ANOVAs, Within school time, MVPA varied significantly by segment (PE: 30.59%, recess: 18.80%, classroom: 5.69%, Substantial opportunities for PA are lost across all school segments in the Swiss context, with girls consistently less active than boys. Based on these findings, segment-specific and gender-sensitive school PA policies are discussed, and a comprehensive school approach to PA promotion is recommended to support more effective and equitable PA promotion among adolescents. German Clinical Trials Register (DRKS00033362). Date of registration: January 25, 2024. Retrospectively registered. Show less

To characterize the clinical, radiological, and molecular characteristics of CNS tumors associated with Noonan syndrome (NS) and other non-Neurofibromatosis type 1 RASopathies. Twenty-four patients with concern for NS underwent clinical and central radiological review in this multi-institutional study. Whole-exome sequencing, RNA sequencing, and methylation analyses of peripheral blood and/or tumor specimens were performed. Nineteen (79%) of 24 participants had NS, 17/19 (89%) of which had a germline The online version contains supplementary material available at 10.1007/s11060-026-05478-7. Show less

To investigate the association between vaginal microbiota structure in early pregnancy and gestational diabetes mellitus (GDM) and to characterize microbial signatures for early screening for GDM. The present study was a nested case-control study recruiting pregnant women from the Nanjing Gulou Maternal-Child Health Center, China. Vaginal swabs were collected before 20 weeks of gestation for 16S rRNA sequencing. Following 1:3 propensity score matching, 45 GDM cases and 135 controls were enrolled. The final analysis included 42 GDM cases and 121 controls. A random forest model was used to explore the genera of vaginal differential microbiota associated with GDM. Based on these findings, latent profile analysis (LPA) was conducted to explore potential types of vaginal microbiota, and logistic regression was used to analyze the association between vaginal microbiota types and GDM. The GDM group exhibited elevated alpha diversity (Chao1 index, The composition and structure of vaginal microbiota in early pregnancy are different in the two groups. The vaginal microbiota in early pregnancy, which is characterized by co-dominated by The online version contains supplementary material available at 10.1186/s12866-026-04910-2. Show less

Schizophrenia primarily depends on pharmacotherapy, which has demonstrated limited efficacy in enhancing cognitive impairments. High-definition transcranial direct current stimulation (HD-tDCS) and computerized cognitive remediation therapy (CCRT) hold potential for improving cognitive impairments. This study aims to investigate the effects of combining HD-tDCS with CCRT on cognition and to explore the mechanisms of this approach in schizophrenia. This is the protocol of a randomized controlled trial. Schizophrenia patients will be randomly assigned to one of 4 groups: HD-tDCS + CCRT group (Group 1), HD-tDCS group (Group 2), CCRT group (Group 3), and a control group (Group 4). The central electrode will be personalized using magnetic resonance imaging (MRI)-guided localization in the medial prefrontal cortex (mPFC). CCRT includes 6 therapeutic modules and 10 distinct tasks. Both HD-tDCS and CCRT will be administered once daily, 5 days per week, for 4 consecutive weeks, culminating in a total of 20 sessions. Assessments will occur at baseline (T0), after 10 sessions (T1), after 20 sessions (T2), and after 6 months of follow-up (T3). The primary outcome measure is the change in cognition. We will employ multimodal MRI, serum concentrations of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to explore the underlying mechanisms. An involvement of mPFC and synaptic plasticity in response to HD-tDCS and CCRT is hypothesized. The study will provide empirical evidence for the effectiveness of combined therapy at an individual level, explore its mechanisms, and may ultimately result in personalized medicine. ChiCTR2500102731, https://www.chictr.org.cn/hvshowprojectEN.html?id=276964&v=1.0. Show less

Hemodialysis, as one of the main alternative treatment methods for end-stage renal disease, has received much attention in recent years. Due to the particularity of hemodialysis treatment, patients have a relatively high risk of infection during the treatment process. Hemodialysis nurses, who are the main executors of the treatment operations and have the most contact with patients, have a close relationship with the infection risk of patients. The level of their hospital infection prevention and control literacy is closely related to the infection risk of patients. To explore the current level of knowledge, attitudes, and practices (KAP) of hospital infection prevention and control among haemodialysis nurses in the Sichuan Province, China, and identified their potential categories. This provided evidence-based recommendations for improving infection control management in hemodialysis departments. A cross-sectional study was conducted From July 15 to August 15, 2025 using a convenience sampling method to survey 470 hemodialysis nurses from 78 hospitals in Sichuan Province. Participants were licensed nurses with over 3 months of hemodialysis experience. Data were collected using the A total of 460 valid questionnaires were collected, with an effective response rate of 97.87%. The average scores for knowledge, attitudes, and practices related to hospital infection prevention and control among haemodialysis nurses were 4.67 ± 0.43, 4.59 ± 0.43, and 4.74 ± 0.34, respectively. Three latent profile models were constructed, with the two-class model identified as the optimal solution, which were defined as the "Low KAP Group" (25.9%) and "High KAP Group" (74.1%). Logistic regression analysis revealed that sex, responsibility for infection control, hospital level, annual number of infection control training sessions, organizational support, and work engagement were significant influencing factors ( The KAP level of haemodialysis nurses in hospital infection prevention and control was relatively high. Hospital managers should tailor supportive work environments on the basis of the individual characteristics and work engagement of haemodialysis nurses to improve the KAP level of nosocomial infection prevention and control among haemodialysis nurses. Show less

Recent years have seen a marked increase in the number of patients diagnosed with spinal disorders, including chronic cervical myofascial pain syndrome (CMPS). This article aims to explore the potential of inflammatory process biomarkers in the blood and brain-derived neurotrophic factor (BDNF) as a means to assess the efficacy of collagen mesotherapy in the management of chronic CMPS. The second objective of this article is to evaluate the safety of collagen mesotherapy in chronic CMPS. The study comprised 23 subjects, who were randomly assigned either to the collagen mesotherapy group (n = 11) or the lignocaine mesotherapy group (n = 12). Blood was collected from each patient, and also the subjects were evaluated with the numerical rating scale (NRS) and the neck disability index (NDI). Results Both collagen and lignocaine mesotherapy have been observed to cause a significant reduction in pain intensity (NRS) and disability (NDI) over time, with no significant differences seen between the two interventions. However, the fluctuations in the levels of inflammatory biomarkers (TNFα, IL-1β, IL-6) and BDNF did not correspond with the clinical improvement noted. No adverse events related to the intervention were also observed. The potential of inflammatory biomarkers and BDNF, when assessed in blood serum, to serve as a basis for evaluating the efficacy of collagen mesotherapy in chronic CMPS; remains to be elucidated. Nevertheless, collagen mesotherapy appears to be an effective and safe treatment for chronic CMPS. However, further research in this area is required. Trial registration: NCT06807177. https//clinicaltrials.gov/study/NCT06807177. Show less

Type 2 diabetes mellitus (T2DM) represents a systemic disease that extends beyond metabolic dysfunction to include accelerated neurocognitive decline driven by oxidative stress, inflammation, and insulin resistance. Emerging evidence suggests that essential micronutrients may interact synergistically or antagonistically with biguanides, particularly metformin, to influence neurocognitive function. This systematic review synthesized preclinical and clinical evidence on the interactions between essential micronutrients and biguanides (notably metformin) in modulating neurocognitive outcomes in T2DM. Following PRISMA 2020 guidelines, we systematically searched PubMed, Web of Science, and Scopus for studies published between 2010 and 2025. After screening 226 records in Rayyan, 40 studies met the inclusion criteria. Both preclinical and clinical studies were analyzed descriptively to identify patterns of mechanistic and functional outcomes. Extracted data covered intervention types, doses, duration, biomarkers, and cognitive outcomes. Of the 40 studies, 27 (67.5%) were preclinical and 13 (32.5%) were clinical, spanning 14 countries. Most interventions involved vitamin D, zinc, magnesium, vitamin E, or polyphenols, either alone or combined with metformin. Synergistic effects were observed in 77.5% of studies, with significant improvements in fasting plasma glucose, HbA1c, insulin sensitivity, and oxidative balance. Key molecular pathways involved AMPK, PI3K/Akt, GSK3β, and Nrf2-CREB, which mediated enhanced glucose utilization, mitochondrial function, and synaptic plasticity. Antagonistic effects (10%) were mainly linked to metformin-induced vitamin B12 depletion, which impaired neurotrophic signaling and elevated homocysteine levels. Across studies, neuroprotective benefits correlated with increased BDNF, PSD-95, and SIRT1 expression, and reduced IL-6, TNF-α, and MDA levels. Most (75%) of the studies showed a synergistic interaction between biguanides (metformin) and micronutrients save a few that showed antagonistic interaction. Integrating micronutrient supplementation particularly vitamin D, zinc, and antioxidant compounds into T2DM management enhances both metabolic control and cognitive function. These findings support a paradigm shift toward combined nutraceutical-pharmacologic therapy within clinical and public health frameworks. Future research should focus on dose optimization, mechanistic validation, and long-term clinical evaluation to develop evidence-based, nutrition-sensitive diabetes care models. Show less

Depression is one of the most prevalent and disabling non-motor symptoms in Parkinson's disease (PD), forming a bidirectional relationship with motor dysfunction that worsens quality of life. Pharmacological treatments exhibit limited and inconsistent efficacy, and may lead to adverse interactions. Acupuncture may improve both depressive and motor symptoms by regulating the neuro-immune-endocrine network, but high-quality evidence remains insufficient. This study aims to evaluate the efficacy and safety of acupuncture as an adjunctive therapy for depression in PD and to explore potential biological correlates of clinical changes using predefined serum biomarkers. In this single-center, evaluator-blinded, randomized controlled trial, 88 patients with PD and comorbid depression will be randomly assigned to an acupuncture group or a waitlist control group. The primary outcome is the change in the Montgomery-Asberg Depression Rating Scale (MADRS) score. Secondary outcomes include motor function, anxiety, sleep quality, and overall quality of life. Exploratory analyses will assess serum inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and kynurenine/tryptophan (KYN/TRP) ratio. We hypothesize that adjunctive acupuncture may improve depressive and motor symptoms compared with the control. Exploratory analyses will examine whether clinical changes are associated with changes in relevant biomarkers. This study will provide rigorous evidence for acupuncture as an adjunctive therapy, offering a non-pharmacological strategy to optimize the comprehensive management of PD and disrupt the bidirectional emotion-motor interplay. https://www.chictr.org.cn/, identifier ChiCTR2500113443. Show less

Cleft lip with or without cleft palate (CL ± P) is a common congenital anomaly with complex genetic origins. This study presents a genetic case series of three Ecuadorian families with non-syndromic cleft lip and/or palate analyzed using whole-exome sequencing (WES). We identified rare or novel variants in genes with established or emerging roles in craniofacial development. Bioinformatic analyses—while not supported by functional validation—helped prioritize several candidate variants, including a novel These findings provide exploratory genetic data from an underrepresented Latin American population and highlight the need to include diverse cohorts in genomic research to improve diagnosis and genetic counseling. The online version contains supplementary material available at 10.1186/s12903-026-07796-8. Show less

Identifying high-performing advanced practice nursing roles and understanding the factors that contribute to their effectiveness are critical for advancing professional development, optimizing workforce deployment, and ensuring long-term sustainability in nursing. This study aimed to (1) identify distinct latent profiles of advanced practice nursing among specialist nurses in mainland China, (2) quantitatively examine the individual and contextual factors associated with high performance, as characterized by these profiles, and (3) qualitatively confirm the significant factors using explanatory semistructured interviews in the high-performance groups. A mixed-methods sequential explanatory design was used, in which quantitative data were collected first and subsequently explained through qualitative interviews. Certified specialist nurses from 16 hospitals across urban and rural areas of Shanghai were included. Latent profile analysis (LPA) was conducted using the five domains from the Advanced Practice Role Delineation tool as manifest indicators to classify nurses into distinct performance profiles. Multinomial logistic regression was used to examine potential determinants (e.g., job position) of group membership. Additionally, a backpropagation neural network (BPNN) was developed to rank the importance of contributing factors. Specialist nurses identified as high performers in the quantitative phase were purposively sampled for explanatory semistructured qualitative interviews. Three latent profiles emerged: high performance (26.1%), moderate performance (46.3%), and low performance (27.6%). Compared to APNs, staff nurses had significantly lower odds of belonging to the high-performance group ( Identifying the profiles of advanced practice nursing roles provides valuable insights for optimizing APN performance and informing targeted management and policy strategies. High-performing specialist nurses are positioned at the nexus of individual capability, interdisciplinary collaboration, and institutional support. Show less

Atherosclerotic cardiovascular diseases (ASCVDs) remain the primary cause of morbidity and mortality. Macrophages are involved in the progression and regression of atherosclerosis, and macrophage amino acid metabolism is important during this process. Here, we identified that the expression of cystine/glutamate antiporter Slc7a11 was upregulated by oxidized low-density lipoprotein, and specifically enhanced in the macrophages of atherosclerotic plaques. Macrophage-specific Show less

Hypoxic-ischemic brain damage (HIBD) represents a major cause of neonatal morbidity and mortality, resulting from perinatal oxygen deprivation and impaired cerebral blood flow. This study aims to investigate the neuroprotective effects of Arctiin, a bioactive lignan derived from Neonatal rats at postnatal day 8 were randomly assigned to four groups: Sham-operated (SHAM), Hypoxia-Ischemia (HI), Hypoxia-Ischmia with Solvent control (HI/SO), and Hypoxia-Ischemia treated with Arctiin (HI/Arc). HIBD was induced via unilateral carotid artery ligation followed by exposure to hypoxia. The HI/Arc group was administered Arctiin orally at a dosage of 60 mg/kg daily for seven consecutive days. Behavioral performance, biochemical parameters, histological integrity, and gene expression profiles were assessed to evaluate the neuroprotective efficacy of Arctiin. Arctiin administration resulted in a significant reduction in C-reactive protein (CRP), and total oxidant capacity (TOC). Simultaneously, it enhanced total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF) levels. Histological analysis showed diminished infarct volume in the Arctiin-treated group. Moreover, gene expression studies revealed significant restoration of Neuregulin-1 (NRG-1) in group treated by arctiin. Neurobehavioral assessments further confirmed significant improvements in sensorimotor function in the Arctiin-treated group. Our study provides evidence indicating that Arctiin mitigates hypoxic-ischemic brain damage in rat pups through a synergistic mechanism involving the suppression of inflammation and oxidative stress, coupled with the upregulation of critical neuroprotective genes and proteins, specifically NRG-1 gene expression and BDNF protein levels. Future studies should investigate the precise molecular pathways downstream of NRG-1 that mediate Arctiin's neuroprotective effects. Show less

Clarifying relationships between amyloid, tau, and cognition is crucial to understanding dementia risk, but has been mainly performed in non-Hispanic White (NHW) participants. It is unknown whether findings are generalizable to other ethnoracial groups. We evaluated relationships between amyloid-β (Aβ) positivity, apolipoprotein E allele (APOE) ε4, tau-positron emission tomography (PET) Black (β = 0.28, p < 0.001) and Hispanic (β = 0.34, p < 0.001) participants had higher medial temporal lobe (MTL) tau than NHW participants; however, findings were attenuated when accounting for choroid plexus off-target binding. Hispanic participants showed higher tau in lateral temporal regions compared to NHW and Black participants; however, reducing meningeal off-target binding through erosion demonstrated similar lateral temporal tau across groups. Factors other than amyloid and tau may impact cognition in Black participants. PI2620 off-target ethnoracial differences should be investigated. Show less

Coronary heart disease (CHD) is driven by endothelial dysfunction and chronic vascular inflammation. hsa-miR-2110 (miR-2110) has been associated with adverse cardiovascular outcomes, but its mechanistic role in CHD remains unclear. In this study, miR-2110 expression was quantified in peripheral blood from CHD patients and healthy controls. Functional effects were assessed in EA.hy926 endothelial cells following lentiviral overexpression of miR-2110. The target gene Show less

Study DesignRetrospective Single-center propensity score-matched cohort study.ObjectiveAdjacent segment disease remains a major cause of revision surgery after multilevel lumbosacral fusion, and muscle-preserving approaches may help reduce this risk. This study compared clinical and radiographic outcomes between a muscle-preserving fusion combining standalone anterior plus lateral lumbar interbody fusion (A + LLIF) vs circumferential lateral plus posterior lumbar interbody fusion (L + PLIF).MethodsPatients who underwent multilevel lumbosacral fusion (2016-2023) with either A + LLIF or L + PLIF were included. L + PLIF patients with contraindications to standalone A + LLIF were excluded. Propensity score matching, based on age, BMI, PI-LL mismatch and stenosis severity, yielded 90 1:1-matched patients. The primary outcome was revision surgery. Secondary outcomes included spinopelvic alignment, cage subsidence, and perioperative metrics.ResultsBaseline characteristics were comparable between groups (mean age 57 ± 10 years; median fusion levels: 2 [range 2-4]). The 5-year cumulative incidence of revision surgery was significantly lower with A + LLIF (1/45 events; 2.2%) than with L + PLIF (14/45 events; 31.1%; Show less

Esophageal cancer is a formidable malignancy, presenting a significant health challenge due to its widespread prevalence and associated high mortality rates. Epithelial cell adhesion molecule (EpCAM), a pro-oncogenic glycoprotein, has been identified as an upregulated protein in esophageal adenocarcinoma (ESCA) through multi-OMICS platforms. However, its functional role in ESCA remains relatively understudied. Here, we investigated the contribution of EpCAM to ESCA pathogenesis using an EpCAM-null ESCA cell line, FLO-1, as a gain-of-function model. Introduction of a recombinant EpCAM-GFP fusion construct into FLO-1 cells resulted in enhanced cell migration, adhesion, clonogenic survival, and invasive capacity, supporting a pro-tumorigenic role for EpCAM. To define EpCAM-associated regulatory networks, RNA sequencing was performed on EpCAM-overexpressing cells, revealing 797 differentially expressed genes. Functional enrichment analyses indicated significant involvement of pathways related to cell adhesion, cell motility, transmembrane activity, and neuronal-associated processes, with enrichment in plasma membrane, focal adhesion, and neuron projection terminus compartments. Protein-protein interaction network analysis identified key hub genes, including SOX2, COL1A1, LOX, COL3A1, LUM, PXDN, BDNF, NCAM1, TLR2, and CCL5, linking EpCAM signaling to PI3K-Akt, ECM-receptor interaction, and focal adhesion pathways. Importantly, quantitative polymerase chain reaction (qPCR) validation of selected hub genes confirmed significant upregulation of the extracellular matrix components COL1A1 and PXDN in EpCAM-overexpressing FLO-1 cells, supporting the transcriptomic predictions and implicating ECM remodeling as a downstream consequence of EpCAM signaling. Collectively, these findings demonstrate that EpCAM promotes aggressive cellular phenotypes in ESCA and drives transcriptional programs associated with adhesion, invasion, and extracellular matrix regulation, highlighting potential therapeutic vulnerabilities in EpCAM-driven ESCA. Show less

B-cell maturation antigen (BCMA) is the main target for chimeric antigen receptor (CAR)-T cells in multiple myeloma (MM), demonstrating promising outcomes. However, unlike what happens with CART19 in lymphoblastic leukemia and non-Hodgkin's lymphoma, a high proportion of patients will relapse after CAR-T BCMA therapy due to insufficient antigen expression, low CAR-T cell persistence and/or T-cell exhaustion. In other B cell malignancies, second-generation anti-CD19 4-1BB CARs with CD28-transmembrane domain (TMD) have shown high efficacy and a favorable toxicity profile. We have developed a second-generation CD8α-TM BCMA-4-1BBζ CAR-T product, ARI0002h (Cesnicabtagene-autoleucel) for patients with relapsed/refractory MM. We hypothesized that replacing the TMD of ARI0002h with a CD28-TMD could increase efficacy and reduce tumor escape while maintaining a tolerable toxicity profile. We generated CAR-T cells using T-cells isolated from buffy coats and evaluated the efficacy and fitness of CAR-Ts at day 8-10 of expansion against several MM cell lines. In vitro analyses included cytotoxicity, proliferation, cytokine secretion, T-cell subset markers, activation and exhaustion profiling, metabolomic assays, and RNA-seq after multiple tumor challenges. In in vivo xenograft studies using NSG mice, with tumor cells expressing GFP-ffLuc, disease progression was monitored weekly via bioluminescence imaging. Despite showing similar in vitro performance regarding cytotoxicity, proliferation and cytokine production, ARI2h-TM28 outperforms ARI0002h in a low BCMA expression setting and achieves superior in vivo tumor control and survival in relapse models with antigen downregulation. Furthermore, ARI2h-TM28 showed an optimized metabolic profile, more oxidative and energetic compared with ARI0002h, with downregulation of proinflammatory genes in CD8 T cells, contributing altogether both to reduced exhaustion and increased persistence of the CARs, improving their efficacy in preclinical models. Incorporating a CD28-TMD into the ARI0002h CAR enhances tumor control even in relapse models with downregulation of the target antigen, offering improved long-term disease management. This modification increases potency against MM tumor cell lines with both normal and reduced BCMA expression, demonstrating superior metabolic endurance and in vivo activity. Show less

The approach to physical activity in patients with epilepsy has substantially changed over the last decade. Despite multiple positive effects of physical activity on general health and well-being, patients with epilepsy have long been advised not to engage in sports activities. Recent studies have led physicians to formulate updated recommendations and to encourage patients to remain active. It has been demonstrated that sport does not increase seizure prevalence, and the rate of sport-induced injuries in people with epilepsy is comparable to that of the general population. Additionally, physical activity modulates brain plasticity through a number of mechanisms, including the effect of brain-derived neurotrophic factor (BDNF), gamma-aminobutyric acid (GABA)/glutamate balance, and maintaining long-term potentiation states in synapses. The International League Against Epilepsy (ILAE) classifies sports into three categories according to the potential risk of injury in the event of a seizure. While most activities fall into low- or moderate-risk groups, high-risk sports include aviation, climbing, diving, horse racing, motor sports, parachuting, rodeo, scuba diving, ski jumping, solitary sailing, surfing, and windsurfing. Qualification for sports participation requires individual assessments of predispositions, seizure type and frequency, reaction to specific sports disciplines, respiratory function, and adjustment of hydration and nutrition. The intensity of training should be increased gradually to avoid triggering factors, such as hyperventilation, alkalosis, and hyperthermia. Seizure occurrence differs between aerobic and anaerobic sports, which is another aspect that needs to be included. Exercise electroencephalographic (EEG) and ambulatory EEG monitoring should be taken into account in patients with exercise-induced seizures to optimize their training plan. Despite the evolving recommendations, it is difficult to formulate universal recommendations for everyone. Each patient with epilepsy should undergo an individual qualification process and be appropriately monitored. Show less

This study investigated longitudinal plasma serotonin dynamics across the Alzheimer's disease (AD) continuum (cognitively normal [CN], mild cognitive impairment [MCI], and AD) to determine whether baseline serotonin and its 24-month change are associated with CSF amyloid-β (Aβ42), tau biomarkers, amyloid PET burden, structural brain integrity, and cognitive decline. Data from 959 ADNI participants (CN = 306, MCI = 421, AD = 232) with baseline and 24-month follow-up were analyzed. Measures included plasma serotonin, CSF biomarkers (Aβ42, total tau, p-tau181), florbetapir PET, MRI (hippocampal volume, cortical thickness), and cognitive tests (MMSE, ADAS-Cog 11, CDR-SB). Group differences were tested using ANOVA or Kruskal-Wallis, and associations were examined via partial correlations and mixed-effects models adjusted for age, sex, education, and APOE ε4, with FDR correction. The results revealed that baseline plasma serotonin levels showed a stepwise decline across the clinical continuum (CN > MCI > AD; p ≤ 0.05), consistent with progressive serotonergic dysregulation. In AD participants, higher baseline serotonin was significantly associated with less amyloid pathology and preserved brain structure, including higher CSF Aβ42 (β = 0.28, FDR p = 0.01), lower florbetapir PET SUVR (β = -0.31, FDR p = 0.02), and larger hippocampal volume (β = 0.33, FDR p = 0.02). Higher serotonin was also linked to better cognitive performance (MMSE: β = 0.22, FDR p = 0.02; ADAS-Cog 11: β = -0.24, FDR p = 0.02). Longitudinally, decreases in serotonin over 24 months in AD were associated with worsening amyloid burden (ΔPET SUVR: β = -0.29, FDR p = 0.02) and accelerated hippocampal atrophy (β = 0.32, FDR p = 0.01). Baseline serotonin predicted smaller 24-month declines in CSF Aβ42 (β = 0.28, FDR p = 0.01) and reduced hippocampal volume loss (β = 0.31, FDR p = 0.01). In CN and MCI groups, associations between serotonin and AD biomarkers or cognitive outcomes were not significant after FDR correction. On the whole, lower plasma serotonin levels are linked to amyloid pathology, hippocampal neurodegeneration, and cognitive decline in AD, supporting serotonin's potential as a stage-specific biomarker and mechanistic contributor to disease progression. Integrative longitudinal studies are needed to clarify causality and evaluate serotonergic pathways as therapeutic targets. Show less

Malignant phosphaturic mesenchymal tumors (MPMT) are rarely seen soft tissue tumors. They can result in tumor-induced osteomalacia with hypophosphatemia. These tumors show FN1::FGFR1/FGF1 gene fusions. We present a 59-year-old male patient with a swelling in his right knee. Magnetic resonance imaging examination revealed a soft tissue mass with a maximum diameter of 2 cm in his distal right thigh. Histopathologically, the tumor was composed of atypical spindle cells. Coagulative tumor cell necrosis, extensive osteoid-like matrix, calcifications, and aneurysmal bone cyst-like areas were present. Mitotic index was 16/mm Show less

Non-suicidal self-injury (NSSI) is highly prevalent among adolescents with depression, yet the heterogeneity of underlying temperamental risk factors remains poorly understood. Traditional variable-centered approaches fail to capture how distinct affective temperaments co-occur within individuals. This study aimed to identify latent profiles of affective temperaments and examine their association with NSSI, exploring the statistical mediating role of cognitive emotion regulation (CER). A cross-sectional study was conducted from February 2025 to September 2025 at the First Hospital of Hebei Medical University. A total of 290 adolescents (aged 10–19) diagnosed with Major Depressive Disorder were recruited, with 282 valid responses included in the final analysis. Participants completed the TEMPS-A, CERQ, and ASHS. Latent Profile Analysis (LPA) was utilized to identify temperament subgroups. Mediation analysis with bootstrapping was performed to test the indirect effects of CER strategies. LPA identified three distinct profiles: Resilient/Low-risk (Class 1, 32.6%), Anxious-Depressive (Class 2, 46.1%), and Mixed-Dysregulated (Class 3, 21.3%). The Mixed-Dysregulated group, characterized by simultaneous elevations in depressive, anxious, irritable, and cyclothymic temperaments, exhibited the highest frequency (45.2 ± 21.3 times/year) and prevalence (98.8%) of NSSI compared to other groups ( The findings delineate a specific “Mixed-Dysregulated” risk phenotype within adolescent depression that is associated with severe NSSI. Interventions should move beyond standard depression care to target cognitive flexibility and emotional regulation skills. Statistical mediation analysis suggests that this risk is mediated by maladaptive cognitive emotion regulation strategies. Not applicable. Show less

Both brain-derived neurotrophic factor (BDNF) and ovarian hormones are powerful neuromodulators, yet evidence of their impact on human cognition remains mixed. As prior work has studied them in isolation, examining their interacting effects presents a key empirical opportunity for explicating their effects on cognition. We genotyped participants for the BDNF Val66Met single nucleotide polymorphism, which is associated with less efficient activity-dependent BDNF secretion and altered hippocampal function, and examined their performance on a complex learning task at two points in the menstrual cycle: early follicular (characterized by low levels of ovarian hormones) and late follicular (characterized by high estradiol). While met carriers showed advantages during the early follicular timepoint, val homozygotes outperformed them at the late follicular timepoint. Furthermore, effects in met carriers were largely driven by increased sensitivity to both absolute levels and changes in levels of estradiol. The current findings provide the first evidence of BDNF Val66Met interacting with the menstrual cycle to predict cognition, demonstrate nuanced genotype- and hormone-specific outcomes, and underscore the importance of studying effects of interacting biological systems on human cognition. Show less

Poststroke epilepsy (PSE) is a common complication following stroke and is associated with increased mortality and worse functional outcomes. There is no biomarker sufficiently to predict PSE, and antiseizure medications are initiated after the first unprovoked seizure. Early identification of patients at high risk for PSE is needed to consider preventive measures and improve management strategies. Illumina miRNA sequencing was performed on serum collected at follow-ups of patients with PSE and compared to ischemic stroke patients without epilepsy and patients with epilepsy without stroke ( miRNA profiling revealed significant differences among the groups, with miR-10b-5p expression reduced in PSE patients compared to those with stroke alone. miR-486-5p was significantly reduced in PSE patients compared to epilepsy patients. qPCR validation confirmed miR-10b-5p as a potential biomarker candidate to distinguish PSE patients from stroke patients without PSE. BDNF, a key regulator of post-stroke recovery and epileptogenesis, was identified as a primary target of miR-10b-5p. While no group-level differences in serum BDNF concentrations were observed, BDNF levels correlated with disease duration and seizure latency exclusively in the PSE group. Importantly, as samples were obtained during follow-up rather than the acute post-stroke phase, our results indicate an involvement of the miR-10b-5p/BDNF axis in long-term post-stroke remodeling or general PSE susceptibility rather than a predictive biomarker. However, the miR-10b-5p/BDNF axis may represent a biologically plausible pathway associated with post-stroke epileptogenesis and impaired post-ischemic recovery. Prospective longitudinal studies with early post-stroke sampling are required to determine its predictive value. Show less