Annals of medicine最新文献

Background and aims: Hepatocellular carcinoma (HCC) recurrence was previously characterized into four types, and patients with progression/hyper-progression recurrence (type III-IV) have an extremely poor prognosis. However, the immune background of resectable HCC, particularly in patients who experience recurrence, remains underexplored. Therefore, this study aimed to describe the immune landscape of resectable HCC, especially postoperative type III-IV recurrent HCC, and explore potential immune-targeted anti-relapse strategies for treated populations.

Methods: The differences in gene expression in patients with recurrent HCC (type I-II (solitary or multi-intrahepatic oligo recurrence) vs. type III-IV) were investigated using bulk sequencing. Multiple immune infiltration methods (single-sample gene set enrichment analysis (GSEA), Microenvironment Cell Populations-counter and ESTIMATE) were used, and patients were divided into four groups to identify four distinct immune subtypes: immune-enrichment/matrix-poor (IE1), immune-enrichment/matrix-rich (IE2), immune intermediate/matrix-rich (ITM) and immune desert/matrix-poor (ID). Co-expression and protein interaction analyses were used to identify characteristic genes in ITM closely associated with type III-IV recurrence, which was matched with drug targets for Huaier granules (HG) and lenvatinib. Virtual docking was used to identify potential therapeutic targets, and the results were verified using single-nuclei RNA sequencing and histological analysis.

Results: ITM was closely related to type III-IV recurrence and exhibited immunotherapy potential. The potential efficacy of inhibiting CCNA2, VEGFA, CXCL8, PLK2, TIMP1, ITGB2, ALDOA, ANXA5 and CSK in ITM reversal was determined. Molecular docking demonstrated that the proteins of these genes could bind to HG or lenvatinib. The immunohistochemical findings demonstrated differential VEGFA (p < .01) and PLK2 (p < .001) expression in ITM type and ID in type III-IV recurrent HCC.

Conclusions: Three primary immunotypes of resectable HCC (IE2, ITM and ID) were identified, and HG and lenvatinib could potentially overcome immune checkpoint blockade (ICB) resistance in ITM patients with HCC, particularly those classified as type III-IV.

Background: Both the number of risky health behaviours and the duration of exposure to these behaviours over time may increase the risk of later adverse outcomes. This study examined cumulative associations of risky health behaviours with both positive and negative aspects of mental well-being and health. It has a uniquely long follow-up period of over 30 years, from early adulthood to the beginning of late adulthood.

Materials and methods: The data were from the Jyväskylä Longitudinal Study of Personality and Social Development. The participants represent the Finnish age cohort born in 1959. This study utilized data collected at ages 27 (1986), 36 (1995), 42 (2001), 50 (2009), and 61 (2020-2021) (n = 206-326). Risk scores indicating the current number of risky behaviours of smoking, heavy alcohol consumption, and physical inactivity and their temporal accumulation over time were calculated. The associations of risk scores with mental well-being (depressive symptoms, psychological well-being) and health (self-rated health, number of metabolic risk factors) from age 36 onwards were analyzed with linear multilevel models adjusted for gender and education.

Results: More current risky behaviours were associated with more depressive symptoms (B = 0.10, p = 0.032), lower psychological well-being (B = -0.10, p = 0.010), lower self-rated health (B = -0.45, p < 0.001), and more metabolic risk factors (B = 0.53, p = 0.013). The associations of temporal risk scores with the outcomes were even stronger (depressive symptoms: B = 0.38, p < 0.001; psychological well-being: B = -0.15, p = 0.046; self-rated health: B = -0.82, p < 0.001; metabolic risk factors: B = 1.49, p < 0.001). Among individual behaviours, the temporal risk score of alcohol consumption was negatively associated with most outcomes, while smoking was associated with poorer mental well-being and physical inactivity with poorer health.

Conclusions: The current and temporal accumulation of multiple risky health behaviours were associated with poorer mental well-being and health. Preventing these behaviours early in adulthood and midlife is crucial to avoid their accumulation and subsequent health risks.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases, with a range of manifestations, such as hepatic steatosis. Our previous study showed that Kaili Sour Soup (KSS) significantly attenuated hepatic steatosis in rats. This study explored the main components of KSS and the mechanisms by which it exerts its protective effects against NAFLD.

Methods: Twenty-four 6-week-old male Sprague-Dowley (SD) rats were randomly assigned to three treatments: feeding a normal standard diet, a high-fat diet, or a high-fat diet plus gavage KSS. The effects of KSS treatment on hepatic lipid accumulation were assessed using biochemical, histological, and molecular experiments. The amounts of KSS ingredients were measured using biochemical assays. Network pharmacology analyses were performed to identify the hub genes of KSS targets and enriched pathways. CCK-8 assay was used to determine the effect of free fatty acids (FFA), lycopene, and estrogen on HepG2 viability. Quantitative Real-Time polymerase chain reaction (qRT-PCR) and Western blot assays were performed to determine the effect of KSS or lycopene on estrogen signaling and expression of lipid metabolism-related molecules. Statistical analyses were performed using GraphPad Prism and SPSS.

Results: KSS alleviated fat deposition in rat liver tissue and affected the expression of hepatic lipid synthesis, catabolism, and oxidative molecules. Lycopene was identified as the ingredient with the highest amount in KSS. Network pharmacology analyses showed that the hub genes were enriched in the estrogen signaling pathway. Cellular experiments showed that lycopene increased the expression of Estrogen Receptor α (ERα), Carnitine palmitoyltransferase 1 A (CPT1A), Peroxisome proliferator-activated receptor α (PPARα) (all p < 0.01), and Hormone sensitive lipase (HSL) (p < 0.05), and reduced the expression of lipid metabolism-related factors 1c(SREBP-1c) (p < 0.01), Acetyl-CoA carboxylase 1 (ACC) and Lipoprotein lipase (LPL) (all p < 0.05).

Conclusions: KSS ameliorated abnormal lipid metabolism in patients with NAFLD. Lycopene was the major component of KSS, and it affected estrogen signaling and the expression of lipid metabolism molecules. In short, both KSS and LYC could change lipid metabolism by lowering lipid accumulation and raising lipolysis.

Background: Liver X receptors (LXRs) are expressed in placenta and may be associated with pre-eclampsia (PE). Oxysterols act as agonists for LXRs. We recently proposed a new blood pressure-regulating circuit with oxysterol 4β-hydroxycholesterol (4βHC) acting as a hypotensive factor via LXRs.

Materials and methods: This study investigated the association between maternal plasma 4βHC, blood pressure (BP) indices, placental expression of LXR target genes, and patient characteristics using data from the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort. Plasma samples of 144 women with PE and 38 healthy pregnant controls as well as 44 PE and 40 control placental samples were available. In addition, genetic data from the FinnGen project was utilized to explore the associations of LXR alleles with PE and pregnancy hypertension.

Results: There were no significant associations between 4βHC and BP or maternal and perinatal characteristics in FINNPEC cohort. However, plasma 4βHC was inversely correlated with the maternal body mass index. There were no associations with the genetic variants of LXRs with PE in FinnGen. LXR target genes APOD, SCARB1, TGM2, and LPCAT3 were expressed differently between PE and normal pregnancies in placental samples of FINNPEC.

Conclusions: Our results demonstrate that plasma 4βHC and genetic LXR variants do not play a major role in PE and BP regulation during pregnancy. However, key LXR target genes involved in lipid metabolism were expressed differently in normal and PE pregnancies. Further research is needed to understand the complexities of oxysterols, LXRs, and their potential contributions to placental function and pregnancy outcomes.

Introduction: Virtual reality (VR) has been suggested as a promising technology for delivering cognitive training to persons with traumatic brain injury (TBI), as it can provide situations resembling everyday activities. Studies have demonstrated that persons with TBI manage utilizing VR in clinical settings; however, no studies have investigated VR use in home settings. The aim of this study was to explore how persons with TBI experience utilizing VR for rehabilitation at home and how they experience VR as cognitive training.

Methods: Individual qualitative interviews were conducted with ten persons with TBI, aged 18-65. Participants had experience using VR, as they were recruited from the intervention group in a randomized controlled trial investigating VR in cognitive training. The data were analyzed using thematic analysis.

Results: Participants highlighted the importance of creating new routines when fitting VR into everyday life. They addressed how being in a virtual world contributes to their motivation for cognitive training. Three themes were developed: 'Fitting VR-training into everyday life', 'Navigating through change' and 'Being in two worlds at the same time'.

Conclusion: This study shows that participants experienced VR as motivating, engaging, and easy to use, regardless of prior experiences with VR. The participants demonstrated how they included VR in everyday life by creating new routines when they performed cognitive training. Therewere few reports of adverse events. However, some experienced that VR had a negative impact on their energy level. Participants described the importance of therapeutic involvement for individual tailoring of the intervention.

Objective: Damage to the corpus callosum (CC) in amyotrophic lateral sclerosis (ALS) patients has been confirmed via electrophysiological, neuroimaging, and autopsy studies. Additionally, the CC is hypothesized to serve as a pathway for the spread of pathological information. This study aimed to investigate whether the CC plays a mediating role in the symptomatic spread of ALS.

Methods: In this observational study, diffusion tensor imaging (DTI) data were acquired from 45 individuals with the upper motor neuron-dominant (UMN-D) phenotype of ALS. The UMN-D ALS patients were categorized into two groups based on the direction of symptom spread, including 25 patients with horizontal spread (group H) and 20 patients with vertical spread (group V). Diffusivity indices were derived through whole-brain analysis and probabilistic fiber tracking.

Results: According to the voxel-based analysis and tract-based spatial statistics, differences in axial diffusivity (AD) in the CC were observed between disease subgroups, with patients in group H showing higher AD values than those in group V. Fiber tracking analysis revealed persistent differences in the AD indices of CC-primary motor cortex (PMC) fibers between the two disease subgroups.

Conclusion: In UMN-D ALS patients, the direction of symptom spread may be related to the degree of CC involvement. The AD metric may be a more specific indicator of CC damage.

Background: Pancreatitis poses a significant global health burden, disproportionately affecting children and adolescents. This study uses the global burden of disease (GBD) 2021 dataset to evaluate pancreatitis epidemiology in this demographic, focusing on disparities by age, sex, and region.

Objective: To assess global trends in pediatric pancreatitis, identify risk factors, and forecast disease burden to 2035.

Methods: We analysed GBD 2021 data on deaths and disability-adjusted life years (DALYs) for pancreatitis in individuals under 20. The socio-demographic index (SDI) assessed the link between societal development and health outcomes. Bayesian age-period-cohort (BAPC) modelling and Poisson's linear models were applied to project future burdens and estimate annual percentage changes (EAPCs) in age-standardized rates.

Results: In 2021, pancreatitis caused 1120.09 deaths in children and adolescents, comprising 2% of all pancreatitis-related deaths. Age-standardized death rate (ASDR) and DALYs rate declined from 1990 to 2021 (EAPC -0.92 and -0.86, respectively). Low-middle SDI regions, notably Andean and Central Latin America and Eastern Europe, faced the highest burden. Alcohol was a leading risk factor, accounting for 3.51% of related deaths, and males had higher death and DALYs rate.

Conclusions: Despite declining pancreatitis-related mortality and DALYs, the disease remains a challenge, particularly in low-middle SDI regions. Alcohol consumption is a key risk factor, underscoring the need for targeted public health interventions. Gender-, age-, and region-specific strategies are essential to mitigate pancreatitis impact in children and adolescents.

Objective: The fibrinogen/albumin ratio (FAR) is a novel inflammatory indicator, which has been associated with cardiovascular disease. However, the relationship between FAR and cardiovascular event (CVE) in patients with peritoneal dialysis (PD) remains unclear. This study aims to clarify the relationship between FAR and first-ever CVE in patients with PD.

Methods: A total of 278 patients were enrolled between January 2012 and June 2021. They were defined as the high FAR group and the low FAR group based on the median FAR value (0.107). The primary outcome was the occurrence of first-ever CVE. Kaplan-Meier's curves and Cox regression analysis were used to analyse the relationship between FAR and first-ever CVE in patients with PD. Forest plots were employed to depict the relationship between FAR and first-ever CVE in each subgroup.

Results: The average follow-up period was 40.26 ± 28.27 months. A total of 101 (36.3%) patients developed first-ever CVE. Kaplan-Meier's analysis showed that there was a higher risk of first-ever CVE (p = .002) in the high FAR group. Multivariate Cox regression analysis showed that FAR ≥ 0.107 and age were independently associated with the risk of first-ever CVE in patients with PD. Receiver operating characteristic (ROC) analysis showed that FAR had a greater predicting value on the first-ever CVE.

Conclusions: High levels of FAR are independently associated with an increased risk of first-ever CVE in patients with PD.

Background: Application-based interventions have gradually emerged as potential tools for improving the health status of cancer patients. However, the conclusions of existing studies on the effectiveness of app-based intervention in managing breast cancer symptoms vary.

Methods: This study systematically searched the PubMed, Web of Science, Scopus, Cochrane Library, and EMBASE databases from the inception of each database to October 25, 2024. Two researchers independently screened studies, extracted data, and evaluated the quality using the Cochrane Risk of Bias Tool. Data analysis was performed using RevMan 5.3 software, and the effect size was expressed as the standardized mean difference (SMD).

Results: Of 16 included randomized controlled trials, meta-analysis results indicated that, compared to usual care, app-based interventions significantly improved breast cancer patients' quality of life (14 studies, SMD = 0.84, 95%CI = 0.48 - 1.19, p < 0.00005, I² = 90%, GRADE = low), and positively alleviated physical pain and anxiety (5 studies, SMD = - 0.60, 95%CI = -0.92 to -0.29, p = 0.0002, I²= 56%, GRADE = very low; 3 studies, SMD = -0.75, 95% CI = -1.40 to -0.09, p = 0.03, I²= 86%, GRADE = very low). However, no statistically significant differences were observed in improving fatigue (3 studies, SMD = 0.18, 95%CI = - 0.05 - 0.42, p = 0.13, I² = 0%) and depression (2 studies, SMD = -0.65, 95%CI = - 2.12 - 0.82, p = 0.38, I² = 96%).

Conclusion: Application-based interventions can significantly improve the quality of life of breast cancer patients, effectively relieve pain, and reduce anxiety.

Background: Individuals with alcohol use disorder (AUD) often experience symptoms such as anxiety, depression, and decreased sleep quality. Although these are not diagnostic criteria, they may increase dependence risk and complicate treatment. This study aims to analyze comorbidities and their complex relationships in AUD patients through epidemiological surveys and network analysis.

Materials and methods: Using multi-stage stratified cluster random sampling, we selected 27,913 individuals and identified those with AUD for the study. All screened subjects were assessed with the General Health Questionnaire, Pittsburgh Sleep Quality Index, and Simple Coping Style Questionnaire, and diagnosed according to DSM-IV criteria. Network analysis and visualization were performed in R 4.4.0. The qgraph and bootnet packages in R were used to obtain partial correlation network analysis and node centrality of mental health, sleep quality, and coping styles in individuals with AUD through the estimateNetwork function. The bootnet package was used to assess the accuracy and stability of the network. The bnlearn package in R was used to construct directed acyclic graph (DAG) for individuals with AUD using the Bayesian hill-climbing algorithm.

Results: In the partial correlation network, among the three major comorbidity categories, 'anxiety/depression' was most strongly associated with 'sleep quality'. 'Anxiety/depression' and 'sleep quality' had the highest node centrality, with 'sleep latency' also showing notable centrality. The DAG results indicated that 'sleep latency' had the highest probability priority, directly affecting 'anxiety/depression' and key sleep quality symptoms such as 'subjective sleep quality', 'sleep disturbances', 'sleep duration', and 'sleep efficiency', while also indirectly influencing other symptoms.

Conclusions: Among the comorbid symptoms of AUD, sleep latency appears to be a key factor in triggering other comorbid symptoms. This study provides a basis for interventions aimed at reducing the comorbid symptoms of AUD and promoting recovery.