Category: Statistics

Front Med (Lausanne). 2025 Dec 1;12:1547410. doi: 10.3389/fmed.2025.1547410. eCollection 2025.

ABSTRACT

BACKGROUND: Diabetic nephropathy (DN) is characterized by tubular injury and tubulointerstitial fibrosis, leading to progressive renal dysfunction. While dysregulation of autophagy has been linked to DN pathogenesis, the underlying regulatory mechanisms remain incompletely understood. This study aimed to test the hypothesis that transcription factor 3 (TCF3) serves as a critical upstream regulator of autophagy dysfunction in DN by suppressing Netrin-1 expression, thereby promoting epithelial-mesenchymal transition (EMT) through activation of the PI3K/Akt/mTOR pathway.

METHODS: We established a DN rat model using high-fat diet followed by low-dose streptozotocin injection (25 mg/kg). Thirty-five male Sprague-Dawley rats were divided into five groups (n = 6-7/group, with specific numbers clearly defined for each experimental condition): control, DN, DN + vector, DN + TCF3-shRNA lentivirus, and DN + TCF3-shRNA + 3-methyladenine (3-MA). All key experiments were performed with at least three independent biological replicates. In vitro, HK-2 cells were categorized into four groups: normal glucose (NG, 5.5 mmol/L), high glucose (HG, 30 mmol/L), HG with negative control siRNA (HG + si-NC), and HG with TCF3-targeting siRNA (HG + TCF3-siRNA). Western blotting was utilized to determine the expression levels of autophagy-related proteins, EMT-associated proteins, and PI3K/Akt/mTOR signaling pathway-related proteins. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA expression levels of TCF3 and Netrin-1. Additionally, a dual-luciferase reporter gene assay was performed to investigate the interaction between TCF3 and Netrin-1. Statistical analyses were performed using one-way ANOVA followed by Tukey’s post-hoc test, with p < 0.05 considered statistically significant.

RESULTS: We first confirmed that TCF3 expression was significantly elevated in both DN rat kidneys (2.8-fold increase at protein level, p < 0.001) and high glucose-treated HK-2 cells (2.5-fold at protein level, p < 0.001) compared to controls. Both the DN rat model and HG-stimulated HK-2 cells exhibited enhanced EMT markers, with significantly increased α-SMA and vimentin expression (p < 0.001), and decreased E-cadherin levels (p < 0.001). TCF3 knockdown significantly attenuated these EMT changes and increased autophagy markers, as evidenced by decreased P62 levels (p < 0.01) and increased LC3-II/I ratio (p < 0.001) and Beclin-1 expression (p < 0.01). The dual luciferase assay confirmed direct binding of TCF3 to the Netrin-1 promoter, with a 57% ± 4.3% reduction (p < 0.001) in luciferase activity. Mechanistically, TCF3 silencing mitigated HG-induced fibrosis and promoted autophagy by increasing Netrin-1 expression and suppressing the PI3K/Akt/mTOR signaling pathway.

CONCLUSION: Our findings demonstrate that TCF3 functions as a critical negative regulator of autophagy in DN, establishing a novel TCF3-Netrin-1-autophagy regulatory axis. This study provides new mechanistic insights distinct from previous work by demonstrating the direct transcriptional repression of Netrin-1 by TCF3 in renal pathophysiology. The limitation of our study includes the lack of human DN tissue validation and TCF3-specific pharmacological inhibitors. These findings suggest TCF3 as a potential therapeutic target for preventing renal fibrosis in DN through restoration of autophagy function.

PMID:41404576 | PMC:PMC12702734 | DOI:10.3389/fmed.2025.1547410

Front Public Health. 2025 Dec 1;13:1648606. doi: 10.3389/fpubh.2025.1648606. eCollection 2025.

ABSTRACT

BACKGROUND: Fractures are among the most common traumatic injuries in China, with rising incidence driven by population aging, traffic accidents, and sports injuries. They impose a heavy economic burden due to high treatment costs and prolonged rehabilitation. To improve cost efficiency, China launched a nationwide Diagnosis-Related Groups (DRG) payment reform in 2019. While DRG has shown positive effects in controlling costs for chronic diseases, its impact on trauma-related conditions like fractures remains unclear due to clinical complexity and treatment variability. Existing research mostly focuses on epidemiology, lacking economic evaluations under the DRG system. This study aims to assess how DRG reform influences the inpatient cost structure of fracture patients and explore differential effects across comorbidity and fracture types, providing evidence for more refined payment strategies in trauma care.

METHODS: Using data from 12,101 hospitalized fracture patients (ICD-10 codes S22-S92) admitted to a tertiary hospital in Anshan, Liaoning Province between 2018 and 2024, we conducted a structural change analysis to assess shifts in the composition of inpatient costs before and after the introduction of the DRG payment system. An interrupted time series (ITS) model was applied to estimate both the immediate impact and the longitudinal trend changes associated with the DRG reform initiated on July 1, 2019. In addition, gray relational analysis was employed to further examine the relative contribution of different cost categories to overall expenditure.

RESULTS: A total of 12,101 fracture inpatients were included, covering the entire period before and after the DRG reform. Significant changes in the cost structure were observed post-implementation. The median drug cost decreased from 3,416.06 CNY to 2,796.74 CNY (a reduction of 18.1%). Although the proportion of consumables costs slightly increased (median rose from 7,358.12 CNY to 7,465.64 CNY), the growth rate significantly slowed (p < 0.05). Meanwhile, therapeutic costs (median increased from 1,015.38 CNY to 1,200.91 CNY) and the proportion of surgical fees rose, indicating a shift of medical resources toward technical services under DRG. Rehabilitation costs declined in certain fracture types (e.g., femoral fractures, S72), but increased in others (e.g., lower leg fractures, S82), reflecting DRG’s differential effects on treatment stages. Structural variation analysis showed the greatest fluctuation in consumables costs in spinal fracture cases (S32 group, DsV = 2170.42%), while drug costs significantly declined in the S72 group (DsV = -39.78%). Patients with comorbidities experienced more pronounced structural adjustments-for example, the structural variation in the hypertensive group was 15.3% higher than that in the non-comorbidity group (p < 0.01), suggesting stronger cost-control effects of DRG in complex cases. ITS analysis revealed that the DRG reform had a significant impact on costs across various fracture types (p < 0.05). For total costs, S32 fractures exhibited a reversal from a pre-policy increasing trend (β₁ = 1247.93) to a rapid decreasing trend (β₃ = -2467.0). After the DRG implementation, diagnostic costs showed an increasing trend in most fracture types, while decreasing significantly in S32 fractures (β₃ = -227.16); in contrast, S72 fractures demonstrated a notable increase (β₃ = 52.86). Treatment and medication costs generally displayed decreasing trends, with the most pronounced decline observed in medication costs for S32 fractures (β₃ = -355.1). Consumables costs exhibited a divergent pattern, characterized by an anomalous increasing trend in S42 fractures (β₃ = 1578.62). Rehabilitation costs showed a universal decreasing trend, with the most significant control effect seen in S32 fractures (β₃ = -483.58). Gray relational analysis indicated that, before and after DRG implementation, the cost struetures of different fracture types exhibited distinct patterns of change. In S22 and S42 fractures, the correlation coefficients of diagnostic and drug-related costs increased notably, with all categories in S42 rising to 0.89-0.90, reflecting a highly concentrated cost structure. S32 and S82 fractures showed overall stability or slight increases across cost categories. In contrast, S52 and S62 fractures demonstrated a general decline, particularly in therapeutic, consumable, and rehabilitation costs. S72 fractures remained relatively stable, with minimal fluctuations in correlation coefficients. S92 fractures displayed increases across all cost categories with balanced magnitudes, indicating a comprehensive enhancement. Overall, different fracture types exhibited distinct patterns of cost structure adjustment following DRG implementation.

CONCLUSION: The DRG-based payment reform effectively controlled pharmaceutical expenditures while increasing diagnostic costs, leading to fracture-type-specific shifts in treatment structure and highlighting the need for differentiated management strategies. This study provides empirical evidence to support the optimization of DRG payment standards and the advancement of healthcare payment reform.

PMID:41404571 | PMC:PMC12704093 | DOI:10.3389/fpubh.2025.1648606

Front Public Health. 2025 Dec 1;13:1675383. doi: 10.3389/fpubh.2025.1675383. eCollection 2025.

ABSTRACT

OBJECTIVE: To explore the correlation between body mass index (BMI) and cognitive impairment in type 2 diabetes patients through a cross-sectional observational study.

METHODS: Data on basic information and cognitive impairment of type 2 diabetes were collected through questionnaires, and the correlation between BMI and cognitive impairment of type 2 diabetes was analyzed using logistic regression model, restricted cubic spline (RCS) model and subgroup analysis. At the same time, the interaction between BMI and exercise, living status and other factors was tested.

RESULTS: A total of 565 valid samples were included in this study and 51.15% had cognitive impairment. The mean BMI score was 24.51 ± 2.16 kg/m². An inverse association between BMI score and cognitive impairment in patients with was observed in all three models. Subsequent regression analysis using RCS confirmed this nonlinear association and found two inflection points at 23.72 kg/m² and 27.77 kg/m². Specifically, cognitive impairment increased with decreasing BMI at BMI scores <23.72 kg/m², was least expressed in the interval 23.72-27.77 kg/m², and increased with increasing BMI scores >27.77 kg/m². In addition, the interaction between BMI and factors such as exercise and lifestyle was examined, and the results showed that the interaction did not reach the statistical significance level.

CONCLUSION: Observations indicate that the U-shaped relationship between cognitive impairment and BMI observed in middle-aged and older adults with type 2 diabetes was more pronounced in those who live alone and are physically inactive. Although the interaction test was not significant, the subgroup analysis suggested that middle-aged and older adults with type 2 diabetes who live alone and are physically inactive may need to manage their BMI more rigorously.

PMID:41404570 | PMC:PMC12702732 | DOI:10.3389/fpubh.2025.1675383

Front Public Health. 2025 Dec 1;13:1670577. doi: 10.3389/fpubh.2025.1670577. eCollection 2025.

ABSTRACT

BACKGROUND: Frailty is a common geriatric syndrome that imposes a heavy disease burden globally. Indoor ventilation is a crucial measure for improving air quality. However, the association between indoor ventilation frequency (IVF) and frailty remains unclear. This study aimed to explore this association among Chinese older adults.

METHODS: We used data from 5,511 older adults in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2018 and an external validation sample of 718 older adults from Chongqing. Logistic regression models and linear regression models were employed to assess the association between IVF and frailty and its seasonal variations. We further conducted subgroup analysis to examine differences across various populations. All statistical analyses were performed using SPSS 25.0 and R 4.3.0.

RESULTS: Compared with low ventilation frequency, intermediate (OR = 0.722, 95% CI: 0.559 ~ 0.933) and high (OR = 0.824, 95% CI: 0.643 ~ 0.995) frequencies were significantly associated with a lower risk of frailty. Seasonal analysis revealed that this inverse association was particularly significant in autumn and winter. Subgroup analysis suggested that this association was more pronounced in subgroups such as females, older adults over 80 years old, and those who use non-clear energy for cooking. External validation data from Chongqing supported these findings.

CONCLUSION: This research demonstrated a significant association between IVF and frailty among Chinese older adults. These findings provide supportive evidence for considering ventilation behavior in public health strategies aimed at promoting healthy aging.

PMID:41404569 | PMC:PMC12704094 | DOI:10.3389/fpubh.2025.1670577

Front Public Health. 2025 Dec 1;13:1631596. doi: 10.3389/fpubh.2025.1631596. eCollection 2025.

ABSTRACT

Acquired Immunodeficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV), remains a major public health problem in Brazil. Infection rates vary greatly between regions and states. The North region, in particular, has a higher number of cases, making it a long-lasting challenge, especially in a region with many social and economic challenges. This ecological, descriptive, and analytical study examined AIDS trends across Northern Brazilian states from 2013 to 2023 using data from Brazil’s Notifiable Diseases Information System (SINAN), Mortality Information System (SIM) and national HIV/AIDS epidemiological reports. Our R-based analytical approach incorporated descriptive statistics, Joinpoint regression, linear modeling (calculating trend coefficients, determination coefficients, and p-values with significance at p < 0.05), plus heatmap clustering with dendrograms to evaluate inter-state rate patterns. Spatial variation analysis revealed distinct epidemiological patterns: four states (Amazonas, Amapá, Tocantins, and Rondônia) showed declining detection rates, while Acre experienced a concerning >90% increase despite stable mortality rates. These findings emphasize important groups of cases and identify which states should prioritize public health efforts. This information can assist in more effectively allocating resources to areas with the most cases.

PMID:41404554 | PMC:PMC12702984 | DOI:10.3389/fpubh.2025.1631596

Food Sci Nutr. 2025 Dec 15;13(12):e71358. doi: 10.1002/fsn3.71358. eCollection 2025 Dec.

ABSTRACT

This systematic review and meta-analysis aimed to evaluate the effects of quercetin (QE) on liver function, lipid profiles, kidney function, anthropometric measures, hematological markers, and inflammatory markers in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). PubMed, Cochrane Library, Web of Science, and Embase were searched to January 26, 2025, for randomized controlled trials (RCTs). Additional gray literature sources, trial registries, and preprint platforms were screened. Weighted mean differences (WMDs) with 95% confidence intervals were calculated. Heterogeneity was assessed using the I ² statistic, and meta-regression analyses explored the influence of quercetin dose, baseline BMI, and age. Seven RCTs (540 patients) were included. Quercetin significantly reduced liver enzymes (ALT, AST, GGT), direct bilirubin, and C-reactive protein. Lipid profiles improved with reductions in total cholesterol, LDL, and triglycerides, and an increase in HDL. No significant effects were observed on kidney function, BMI, body fat, hematological markers, or TNF-α. Meta-regressions suggested dosage, baseline BMI, and age may contribute to heterogeneity. According to GRADE, the certainty of evidence ranged from very low to moderate. QE shows preliminary evidence of improving liver function, lipid profiles, and inflammation in MASLD patients. However, given the small number of RCTs and the generally limited certainty of evidence, these findings should be interpreted with caution. Further large-scale, high-quality trials are warranted to confirm its therapeutic role. PROSPERO Registration Code: CRD42025639487.

PMID:41404533 | PMC:PMC12703814 | DOI:10.1002/fsn3.71358

Brain Commun. 2025 Dec 15;7(6):fcaf445. doi: 10.1093/braincomms/fcaf445. eCollection 2025.

ABSTRACT

Clearing amyloid-β pathology in Alzheimer’s disease (AD) has been considered a prerequisite for restoring cognitive functions. Intriguingly, by application of a modality of scanning ultrasound (SUS) to mice that does not remove amyloid-β, we previously achieved significant cognitive improvements. This prompted us to explore SUS as a non-invasive brain stimulation strategy in an open-label safety trial in AD. We conducted a human pilot study in 12 participants with AD with the primary objective of determining feasibility, safety and tolerability. Exploratory secondary end-points were cognitive and behavioural measures, resting-state EEG and functional MRI. A portable device termed UltraThera^Pilot was built under medical device standard guidelines, integrating a Brainsight image-guided neuronavigation system. A single-element 286-kHz transducer was programmed to deliver non-derated ultrasound doses of 2.6, 1.95 or 1.3 MPa. With four treatment sessions spaced fortnightly, four participants received 30 sonications per session (precuneus, ∼30 cm³ brain tissue) and the remaining 8 received 100 sonications per session (bilateral precuneus and temporo-parietal association cortex, ∼100 cm³). Safety monitoring, EEG, MRI, cognitive and neuropsychiatric evaluations were performed. The treatment was fast, safe and well-tolerated at the 1.95 MPa dose. MRI showed no changes, whereas changes were observed in aperiodic EEG content. Cognitive performance did not change but statistically significant improvements in behavioural and psychological symptoms were found using the Neuropsychiatric Inventory test. In conclusion, this SUS safety trial met its primary and secondary end-points in biomarker-confirmed mild-to-moderate AD. It informs our future work in an upcoming efficacy trial in an AD population.

PMID:41404527 | PMC:PMC12703879 | DOI:10.1093/braincomms/fcaf445

Brain Commun. 2025 Dec 16;7(6):fcaf476. doi: 10.1093/braincomms/fcaf476. eCollection 2025.

ABSTRACT

Despite a decline in severe neonatal brain injury in preterm infants, neurodevelopmental impairment remains prevalent. Identifying early biomarkers for neurodevelopmental impairment, particularly in infants without severe neonatal brain injury, is crucial for intervention. This study explores whether brain dysmaturation, indicated by functional connectivity alterations at term-equivalent age, predicts neurodevelopmental impairment severity at 24 months corrected age in preterm infants without severe neonatal brain injury. In this observational cohort study, preterm infants born < 31 weeks’ gestation without severe neonatal brain injury underwent resting-state functional MRI at term-equivalent age. Neurodevelopmental outcomes at corrected age 24 months were assessed using Bayley-III cognitive and motor composite scores, cerebral palsy severity, and neurosensory impairments. Functional connectivity alterations were analyzed in relation to cognitive, language, and motor outcomes. Machine learning models were applied to assess the predictive value of functional connectivity features alongside neonatal exposures for neurodevelopmental impairment severity. Among the 122 preterm infants, 89 (73%) infants had no/mild neurodevelopmental impairment, 27 (22%) had moderate neurodevelopmental impairment, and 6 (5%) showed severe neurodevelopmental impairment. Compared with the no/mild neurodevelopmental impairment group, the moderate/severe neurodevelopmental impairment group was significantly lower in gestational age, and required longer durations of invasive mechanical ventilation, oxygen therapy, vasopressors, and total parenteral nutrition during admission. Compared with term-born controls, a clear trend emerged across neurodevelopmental impairment severity levels: as impairment increased from the no/mild group to the moderate and severe groups, the clustering coefficient increased, whereas the global efficiency decreased. Statistical comparisons between the no/mild and moderate/severe groups, relative to term-born controls, confirmed these patterns (clustering coefficient: t = -4.38, P < 0.001; global efficiency: t = 3.44, P < 0.001). Infants with no/mild neurodevelopmental impairment exhibited enhanced connectivity in the limbic system (t = -5.21, P < 0.001) and between the thalamus and basal ganglia (t = -5.9, P < 0.001), but this compensatory connectivity weakened with increasing neurodevelopmental impairment severity. The thalamo-cortical (frontal lobe, limbic system), thalamo-basal ganglia, and thalamo-cerebellar connectivity were strongly associated with cognitive, language, and motor performance at follow-up. A predictive model incorporating these functional connectivity features and neonatal adverse exposure parameters achieved 82% accuracy. Distinct disruptions in functional connectivity at term-equivalent age in very preterm infants without severe neonatal brain injury may predict the severity of later neurodevelopmental impairment. Early functional connectivity assessment holds promise as a biomarker for identifying high-risk infants who may benefit from timely neurodevelopmental interventions.

PMID:41404526 | PMC:PMC12704428 | DOI:10.1093/braincomms/fcaf476

Brain Commun. 2025 Dec 9;7(6):fcaf478. doi: 10.1093/braincomms/fcaf478. eCollection 2025.

ABSTRACT

In Alzheimer’s disease (AD), accelerated long-term forgetting (ALF), where information is retained normally over 10-30 min but lost at an accelerated rate over subsequent days to weeks, develops several years before symptom onset. However, the neuroanatomical changes underpinning ALF remain undetermined. Eighteen presymptomatic autosomal dominant AD mutation carriers and 12 non-carriers underwent ALF assessment with a list, a story, and visual figure, testing 30-min and 7-day recall of each, separately. T₁ and diffusion-weighted MRI were acquired. Cortical thickness was estimated for 13 pre-defined grey matter regions, with streamline tractography assessing associated structural connectivity. In mutation carriers, lower verbal ALF performance (list and story) was strongly associated with thinner prefrontal cortex (PFC) across four contiguous regions bilaterally. This association was absent in non-carriers. No associations were found between ALF and the thickness/volume of medial temporal lobe (MTL) structures. The association between ALF and PFC connectivity was weaker than for cortical thickness. Our results suggest that early subtle pathological change in PFC underpins ALF development, highlighting the central role of PFC dysfunction in very early AD-related cognitive decline. ALF may represent a qualitatively different (non-MTL driven) form of forgetting compared with the short interval forgetting that develops at later disease stages.

PMID:41404525 | PMC:PMC12704326 | DOI:10.1093/braincomms/fcaf478

Brain Commun. 2025 Dec 4;7(6):fcaf477. doi: 10.1093/braincomms/fcaf477. eCollection 2025.

ABSTRACT

Patients with acute hemispheric stroke exhibit various visuospatial impairments. While many recover rapidly, others remain impaired. Better defining which symptoms characterize the acute and chronic phases and which brain areas and connections are implicated could help to improve diagnostic and rehabilitation tools and inform effective rehabilitation strategies. Here, we report a systematic anatomo-functional study of two populations of acute and chronic hemispheric stroke patients (cross-sectional design). Patients were examined by a series of neuropsychological tests assessing different post-stroke clinical manifestations in the visuospatial domain. We first performed a statistical factorial analysis of patients’ behavioural performance across tests to break down symptoms into coherent profiles of co-varying deficits and determine whether any factors may be specific to each post-stroke phase. We then conducted voxel- and atlas-based lesion-symptom mapping, as well as disconnection-symptom mapping in the two populations. We found different patterns of behavioural impairment across groups, with acute symptoms mostly characterized by lateralized attentional deficits and chronic symptoms manifesting as constructional spatial impairments. Lesions to and/or disconnections of frontal and precentral gyri correlated with lateralized visuospatial symptoms in the acute but not chronic phase, whereas lesions to and/or disconnections of temporoparietal areas correlated with constructional deficits in the chronic phase. Our results indicate that constructional spatial deficits and damage/disconnection of dorsoventral higher-order visual areas most pervasively impair stroke patients in the long term. Such deficits might be overlooked or disregarded by rehabilitation strategies focusing on the (mainly acute) lateralized component of their visuospatial deficits and ignoring concomitant, more object-based deficits. This work may help design more specific diagnostic tests and guide future rehabilitation strategies, ultimately promoting better and more extensive recovery beyond lateralized deficits in attention and spatial awareness.

PMID:41404524 | PMC:PMC12704327 | DOI:10.1093/braincomms/fcaf477