Advances in medical sciences最新文献

Purpose: Patients with meningiomas mostly present good outcomes and optimal prognosis, but different grades of tumors have very different symptoms and recurrence rates. Therefore, effective diagnosis is crucial for early intervention and controlling tumor development. Circadian cycle and autophagy have both been proven to be related to neoplasm formation and pathogenesis; however, there is limited exploration and discussion on the relationships between the circadian cycle and autophagy in patients with meningiomas. This study was undertaken to elucidate the relationship between two autophagy markers (Beclin1, LC3B) and one circadian marker (NR1D1) with clinicopathological parameters in patients with meningiomas.

Materials and methods: Clinicopathological data of 124 enrolled patients were collected. Tissue-sectioned slides were analyzed via immunohistochemical stains and the relationship between the markers was evaluated.

Results: Individually low expression of NR1D1 and Beclin 1 was associated with better prognosis, lower pathological grade, and longer survival. Although correlation analysis showed that NR1D1, Beclin 1 and LC3B were related to each other. However, the dual marker NR1D1-/Beclin 1- was effective in predicting good prognosis in meningiomas, whereas NR1D1-/LC3B- was not.

Conclusion: NR1D1 and Beclin 1 could be adopted as a single marker or coupled as a combined marker to predict meningioma prognoses, pathological grades, and survival. This study provides insights into the association between autophagy and circadian cycles and may benefit future elucidation of molecular mechanisms.

Purpose: Pneumonia, respiratory failure, and fracture are common and highly burdensome for adults with cerebral palsy (CP). To date, there are no clinically friendly tools to assess individualized risk of these outcomes for adults with CP. The objective was to develop and validate prognostic models for 5-year risk of pneumonia, respiratory failure/collapse, and fracture for adults with CP.

Patients and methods: This single medical center retrospective cohort study used medical records from January 1, 2012 till June 1, 2024 from adults ≥18 years old with CP. The development cohort (n=1,520) included those with a start date of follow-up from January 1, 2015 till December 31, 2015 and evidence of being treated at the medical center for ≥3 years prior to day 0. The 5-year risk of outcomes was modelled using logistic regression and variations of the following predictors that were collected during the 3-year baseline: age, sex, Whitney Comorbidity Index, pneumonia, respiratory failure/collapse, fracture, and asthma/COPD. Discrimination (c-statistic) and calibration statistics assessed the model's performance. Decision curve analysis assessed the model's clinical utility. The models were validated in a temporal validation cohort, whose start date of follow-up was January 1, 2016 to May 31, 2019 (n=529).

Results: The prognostic models had good discrimination (c-statistic=0.76-0.78), good-to-excellent calibration, and demonstrated superior clinical utility in identifying true positives and true negatives. All models demonstrated temporal validation.

Conclusions: Prognostic models for 5-year risk of outcomes were developed and temporally validated for adults with CP using measures that can be easily collected from medical records.

Purpose: Therapeutic plasma exchange (TPE) is the treatment of choice in various neuro-immunological disorders in pediatric populations. This study assesses the safety and efficacy of TPE in this demographic.

Materials and methods: A single-center, retrospective cohort study involving pediatric patients who experienced neuro-immunological events and underwent TPE procedures at a tertiary referral center was conducted.

Results: The study included 81 patients (Guillain-Barre: 65, polyneuropathies: 5, myasthenia gravis: 8, multiple sclerosis: 3), undergoing collectively 360 TPE procedures. Fresh frozen plasma (FFP) was used in 76.1% of the TPE procedures. Adverse events (AEs) occurred in 50% of TPEs using FFP compared to 39.5% without. For procedures with at least two AEs, the rates were 24.5% with FFP vs 8.1% without. Incidence of allergic AEs was significantly higher in the FFP group (94.2% of TPE with at least one AE) compared to those without FFP (47.2%). Serious AE accounted for 1.2% of TPE procedures and 2.5% of patients. Effectiveness evaluations using a scale developed for this study and the Hughes Functional Grading Scale showed no significant clinical pre-treatment differences. After completing the treatment, children in the polyneuropathies group had the most severe clinical condition, and the largest relative improvement in clinical status was in the myasthenia gravis group.

Conclusions: TPE conducted by filtration is an effective and safe therapy for pediatric neuro-immunological diseases, with benefits outweighing the risks of complications. The use of FFP in therapy increases the probability of AE by 27%, and significantly raises the risk of allergic and multiple AEs.

Purpose: In this study, we examined novel autoantibodies targeting tumor-associated antigens (TAAs) as biomarkers for clinical assessment of hepatocellular carcinoma (HCC) in a Chinese population.

Methods and methods: A total of 119 patients with HCC and 130 healthy control (HC) volunteers who were age and gender matched were enrolled. The levels of circulating IgG antibodies were detected using an enzyme-linked immunosorbent test (ELISA) developed in-house with linear peptide antigens derived from Annexin A1(ANXA1) and proto-oncogene protein (MYC). The significant level was set at P<0.025 as two tests were performed.

Results: In comparison to the HC group, plasma level of ANXA1 autoantibodies was significantly elevated in HCC patients (t=-3.174, P = 0.002) but the change of plasma MYC autoantibody levels failed to reach the significance level (P>0.025). There was a significant increase in these two plasma IgG autoantibodies in male HCC patients (ANXA1: t=-3.590, P<0.001; MYC: t=-2.706, P=0.007). Pearson correlation analysis demonstrated that both anti-ANXA1 and anti-MYC IgG levels had a positive correlation with BCLC staging (both P <0.025) but a negative correlation with plasma albumin (Alb) (both P <0.025). The area under the ROC curve (AUC) values were 0.613 for anti-ANXA1 IgG assay and 0.567 for anti-MYC IgG assay. The anti-ANAXA1 IgG assay showed a high sensitivity of 31.4% against the specificity of 90.0% for detection of BCLC stages C+D.

Conclusions: Plasma anti-ANXA1 and anti-MYC autoantibodies are likely to serve as a potential biomarker for clinical assessment of HCC prognosis, particularly in male patients.

Purpose: Proper functioning of the endothelial barrier is crucial for cardiovascular system homeostasis. Oxidative stress can lead to endothelial dysfunction (ED), damaging lipids, proteins, and DNA. Reactive oxygen species also increase cytoplasmic Ca²⁺ levels, activating transient receptor potential melastatin 2 (TRPM2), a membrane non-selective calcium channel. The study aimed to assess TRPM2's significance in vascular endothelial cells' response to oxidative stress and the potential use of TRPM2 direct and indirect inhibitors in the prevention of oxidative stress-induced ED.

Materials and methods: EA.hy926 endothelial cells were exposed to hydrogen peroxide for 24 ​h to mimic oxidative stress conditions. To assess the significance of TRPM2 in the response of EA.hy926 ​cells to hydrogen peroxide TRPM2 siRNA as well as direct (N-(p-Amylcinnamoyl)anthranilic acid, flufenamic acid) and indirect (3-aminobenzamide, 3,4-dihydro-5[4-(1-piperidinyl)butyl]-1(2H)-isoquinolinone) TRPM2 inhibitors were tested.

Results: Results showed that hydrogen peroxide-induced ED is alleviated by TRPM2 downregulation. Moreover, preincubation of cells with both direct and indirect TRPM2 inhibitors for 30 ​min before hydrogen peroxide treatment reduces its negative effects on cell viability, cell migration, and junctional proteins.

Conclusions: The obtained results suggest that TRPM2 channel may be a potential target in therapy and prevention of cardiovascular diseases connected with oxidative stress-induced ED. However, further research is needed for clinical applications of direct and indirect TRPM2 inhibitors.

Purpose: This study aims to evaluate the prognostic value of contrast-enhanced ultrasound (CEUS) combined with tumour markers in patients with hepatocellular carcinoma (HCC) undergoing microwave ablation (MWA).

Methods: MWA patients with HCC were divided into good prognosis (n ​= ​75) and poor prognosis (n ​= ​69) groups. The levels of alpha-fetoprotein (AFP), carbohydrate antigen (CA19-9), and carcinoembryonic antigen (CEA) before and after MWA were analysed using an independent sample t-test. The correlation between prognosis, ablation lesion area, and tumour marker levels were analysed by Pearson's correlation. The diagnostic power of the ablation lesion area combined with tumour marker levels for the prognosis of patients with MWA was analysed using receiver operating characteristic (ROC) curves.

Results: The levels of AFP, CA19-9, and CEA in the good prognosis group were significantly lower than those in the poor prognosis group (all P ​< ​0.001). The levels of all tumour markers were significantly negatively correlated with the prognosis of patients who underwent MWA (all r ​< ​0, P ​< ​0.001) and positively correlated with the area of tumour-ablated lesions (r ​> ​0, P ​< ​0.001). Moreover, the diagnostic efficacy of CEUS combined with tumour markers for the prognosis of patients who underwent MWA was significantly higher than that of either single diagnostic modality.

Conclusions: CEUS combined with tumour marker monitoring can effectively improve the accuracy of prognostic diagnosis in patients with MWA and provide a reference for timely and reasonable treatment and therapeutic evaluation.

Purpose: Defibrillation in shockable rhythm is a well-known key intervention in cardiopulmonary resuscitation (CPR). The aim of this study was to analyze accuracy (the sum of the numbers of true positive results and true negative results, divided by the number of total results) of deciding by paramedics whether the rhythm was shockable or non-shockable.

Methods: In this study 103 paramedics from various regions of Poland participated voluntarily. Study participants were presented with 22 simulated various electrocardiogram (ECG) recordings based on 10-s videos. These rhythms were also assessed using a manual defibrillator with shock-advisory mode known as automated external defibrillator (AED) mode.

Results: Among the 103 participants, the mean of correct answers (correct decision to defibrillate or correct decision not to defibrillate) was 18/22 (83.7 ​%). The highest possible score was achieved by the participant with 22/22 (100 ​%) correct answers, while the lowest was 10/22 (45.5 ​%). The highest score obtained for single rhythm was 97.1 ​% and the lowest was 32 ​%. Mean accuracy of shock-advisory mode was 77.3 ​%.

Conclusions: Improving the quality of paramedic training and continuous quality monitoring (e.g., by analyzing ECG recordings from resuscitations) is essential to improve the accuracy of defibrillation rhythm recognition. The role of the AED mode can be advisory, but is not a substitute for assessment by medical professionals in Emergency Medical Service.

Purpose: Interstitial lung disease (ILD) damages the lungs and can be caused by environmental exposures and collagen-vascular diseases. The systemic immune-inflammation index (SII) is investigated to diagnose and manage ILDs in different etiological diseases. The study aims to examine the usefulness of SII in diagnosing specific ILDs like Sjogren's syndrome (SjS)-ILD, interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF).

Materials and methods: In this cross-sectional study, we included 109 patients with IPAF, IPF, and SjS-ILD. Demographic characteristics, symptoms, lung patterns, autoantibodies, and SII were assessed. Morphologic, serologic, and clinical factors determined the classification of IPAF. Student's t-test, Mann-Whitney U test, Pearson-Spearman's method, and receiver operating characteristic (ROC) curves were used to analyze data.

Results: Male patients were more common in IPF and IPAF, while SjS-ILD had mostly female patients. Raynaud's phenomenon and dry mouth/eyes were more common in SjS-ILD compared to IPF and IPAF. The groups had significant differences in patterns, antinuclear antibody positivity, and SII levels. SII levels differed significantly between IPAF, SjS-ILD, and IPF patients, and were correlated with CRP in IPAF and SjS-ILD. The cut-off value of the SII between IPAF and IPF in patients with ILD was 576.1 with 76.0 ​% sensitivity and 76.0 ​% specificity.

Conclusions: Evaluation of SII provides valuable information for understanding and identifying different disease groups with ILDs.

Purpose: Caloric restriction (CR), the permanent or periodic reduction of caloric intake, is a dietary strategy that promotes longevity and healthspan, yielding multiple beneficial effects, such as improved insulin sensitivity and mitochondrial function, decreased body weight, and mitigation of cardiometabolic risk factors. The purpose of our study was the in silico and in vitro assessment of the effects exerted by pinostilbene on SIRT1 and SIRT6 compared to those of resveratrol, a known activator of these enzymes.

Materials and methods: Molecular docking was carried out to determine the interactions with SIRT1 and SIRT6 and, further, the effect of pinostilbene on their activity was tested in vitro to evaluate if it parallels resveratrol's effects regarding SIRT activation.

Results: Molecular docking indicates that resveratrol and pinostilbene bind similarly to SIRT6, while pinostilbene may be able to activate SIRT1 more efficiently than resveratrol. In vitro activity assays showed that while both resveratrol and pinostilbene activate SIRT1 and SIRT6, the concentration-dependent effects differ. For resveratrol, a greater effect was observed at the medium concentration (25 ​μM), whereas pinostilbene showed a more pronounced activation at the lowest concentration (5 ​μM).

Conclusions: Our results offer a glimpse into the structural features and interactions of pinostilbene and resveratrol with SIRT1 and SIRT6, contributing to understanding their potential roles in various cellular processes regulated by SIRT.