Advances in Clinical and Experimental Medicine最新文献

Introduction: Proton pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs) are generally effective in preventing delayed bleeding and healing artificial wounds after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). This study aimed to review the therapeutic effects of PPIs and H2RAs on damage caused by EMR and ESD.

Material and methods: Thirteen articles were collected between 2002 and 2022 by searching Medlib, ScienceDirect, PubMed, International Scientific Indexing (ISI), Embase, and Scopus databases using valid keywords. The main inclusion criteria were delayed wound healing, bleeding, epigastric pain, intraoperative bleeding, and perforation. The odds ratio (OR) and 95% confidence interval (95% CI) were evaluated using a random or fixed effects model. Data analysis was performed using Stata v. 14.2.

Results: A total of 13 articles including 1,483 patients were analyzed. The results showed that delayed bleeding was significantly less frequent in the PPI group than in the H2RA group (OR = 0.6; 95% CI: 0.39-0.92). Subgroup analysis showed that PPI was more effective in preventing delayed bleeding than H2RA for ESD wounds (OR = 0.65; 95% CI: 0.44-1.08). There was no statistically significant difference between both groups regarding the incidence of epigastric pain, intraoperative bleeding, wound healing, and perforation after endoscopic treatments.

Conclusion: The meta-analysis results reveal that PPI is more effective than H2RA in preventing delayed bleeding after endoscopic treatment, particularly in patients treated with ESD. However, there was no significant difference between PPI and H2RA in terms of intraoperative bleeding, epigastric pain, wound healing, and perforation from endoscopic therapy.

Ceramic is a commonly used material in dentistry for reconstructing missing teeth or their tissues due to its biocompatibility, durability and excellent esthetic properties. Despite these advantages, the ceramic restoration damage remains a significant clinical problem. Its causes can be divided into clinical and laboratory factors. The most known include uneven occlusion, improper preparation, trauma, or parafunctions. This study focuses on characterizing less known laboratory causes of ceramic restoration damage. We reviewed the current literature available in the PubMed and Scopus databases. On the basis of 63 selected studies, 3 basic causes of damage were identified: excessive stresses between the framework and ceramic veneering, poor quality of the connection between the facing layer and the substructure, and defects resulting from the nature of the ceramic material such as defects in the ceramic layer, brittleness and lack of flexibility. The stages of the manufacturing process of various permanent ceramic restorations were presented. By controlling these procedures, we can eliminate the errors, resulting in long-term effective functioning of the ceramic restorations.

The so-called "amyloid cascade hypothesis" provides an elegant explanation of Alzheimer's disease (AD), has motivated the amyloid-lowering therapeutic strategy, and led to the elaboration of a rich experimental and conceptual toolkit for the field to progress. But it might be incorrect. The scientific evidence base supporting the efficacy and safety of current anti-amyloid antibody treatments in AD is weak. Nevertheless, we argue that there is a bias towards the amyloid-lowering therapeutic strategy amongst key opinion leaders in the research and advocacy communities. To demonstrate this, we first focus on the AD lexicon: while any accrual of amyloid on a brain PET scan can now permit diagnosis/definition of AD, lowering positron emission tomography (PET) amyloid is considered disease modification, and treatment-induced side-effects are hidden behind neutral-sounding acronyms: ARIA (amyloid-β (Aβ)-related imaging abnormalities: brain bleeding and swelling) and ARPA (amyloid-β (Aβ) removal-related pseudo-atrophy: brain shrinkage). Second, we underline that drugmakers did not test anti-amyloid antibodies against the best proven interventions and did not adequately inform trial participants of risks, thus violating research ethics of the Declaration of Helsinki on 2 counts. In conclusion, we are critical of over-reliance on the idea that PET amyloid-lowering treatments for AD are a therapeutic revolution as claimed, and consider that optimism does not excuse a lack of scientific, regulatory, and ethical integrity. We argue for rigorous, properly controlled (e.g. donepezil) anti-amyloid trials demonstrating cognitive and functional benefit before accepting amyloid-lowering drugs as the new standard of care for AD patients.

Venetoclax, a BH3 mimetic, is a novel targeted anti-cancer drug with a unique mechanism of action leading to the execution of apoptosis through inhibition of the Bcl-2 protein. The development of venetoclax has revolutionized the treatment paradigm of several hematologic malignancies, including treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL) as well as acute myeloid leukemia (AML) in unfit patients. However, despite the high effectiveness of venetoclax in these diseases, some patients, as in the case with other targeted therapies, develop primary or secondary resistance to the drug. Various mechanisms contributing to the resistance to venetoclax have been elucidated, including selection of mutations in the BCL-2 binding groove which decrease affinity to venetoclax, or compensatory overexpression of anti-apoptotic proteins such as MCL-1. Moreover, alterations in cell metabolism and signaling pathways like MAPK or ERK activation have also been reported, suggesting the resistance to venetoclax is highly complex and involves multiple pathways. This review aimed to describe the mechanisms of resistance to venetoclax in AML, CLL, multiple myeloma, and other hematologic malignancies, as well as to propose a perspective to circumvent it.

Background: Establishing a robust signature for prognostic prediction and precision treatment is necessary due to the heterogeneous prognosis and treatment response of clear cell renal cell carcinoma (ccRCC).

Objectives: This study set out to elucidate the biological functions and prognostic role of ferroptosis-related long non-coding RNAs (lncRNAs) based on a synthetic analysis of competing endogenous RNA networks in ccRCC.

Material and methods: Ferroptosis-related genes were obtained from the FerrDb database. The expression data and matched clinical information of lncRNAs, miRNAs and mRNAs from The Cancer Genome Atlas (TCGA) database were obtained to identify differentially expressed RNAs. The lncRNA-miRNA-mRNA ceRNA network was established utilizing the common miRNAs that were predicted in the RNAHybrid, StarBase and TargetScan databases. Then, using progressive univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis of gene expression data and clinical information, a ferroptosis-related lncRNA prognosis signature was constructed based on the lncRNAs in ceRNA. Finally, the influence of independent lncRNAs on ccRCC was explored.

Results: A total of 35 ferroptosis-related mRNAs, 356 lncRNAs and 132 miRNAs were sorted out after differential expression analysis in the TCGA-KIRC. Subsequently, overlapping lncRNA-miRNA and miRNA-mRNA interactions among the RNAHybrid, StarBase and TargetScan databases were constructed and identified; then a ceRNA network with 77 axes related to ferroptosis was established utilizing mutual miRNAs in 2 interaction networks as nodes. Next, a 6-ferroptosis-lncRNA signature including PVT1, CYTOR, MIAT, SNHG17, LINC00265, and LINC00894 was identified in the training set. Kaplan-Meier analysis, PCA, t-SNE analysis, risk score curve, and receiver operating characteristic (ROC) curve were performed to confirm the validity of the signature in the training set and verified in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) analysis showed that the signature was related to immune cell infiltration.

Conclusions: Our research underlines the role of the 6-ferroptosis-lncRNA signature as a predictor of prognosis and a therapeutic alternative for ccRCC.

Background: The clinical response rate for molecularly targeted medications is limited despite significant advancements in molecularly targeted therapy for hepatocellular carcinoma (HCC). Therefore, it is necessary to find new and robust therapeutic targets for the treatment of HCC. Recent research has shown that mesoderm/mesenchyme homeobox gene 1 (Meox1) is closely associated with cancer progression.

Objectives: The aim of this study was to evaluate the clinical relevance as well as biological function of Meox1 in HCC.

Material and methods: Meox1 protein expression level was identified through immunohistochemistry (IHC) examination of pathological tissues from 25 HCC patients. The aim of the analysis was to investigate the relationship between clinicopathological traits and Meox1 expression. Biological function assays of Meox1 in HCC, including proliferation, colony formation, migration, and invasion, were performed with Huh7 and Hep3B cells.

Results: In this study, Meox1 expression in HCC tissues was significantly higher (p < 0.05) compared to paracancerous tissues. Especially in HCC tissues of patients with cirrhosis, the level of Meox1 expression was significantly elevated when compared to HCC tissues of patients without cirrhosis (p < 0.05). High Meox1 expression was significantly associated with tumor-node-metastasis (TNM) stage (p < 0.05) and the Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.05). Moreover, Meox1 silencing suppressed the proliferation, colony formation, migration, and invasion of Huh7 and Hep3B cells.

Conclusions: Our data reveal that Meox1 may play a crucial role in the development of HCC, and given the function of Meox1 in proliferation and metastasis, targeting Meox1 may offer a promising approach for combined and adjuvant therapeutics of HCC.

Background: The imbalance between supply and demand for organ donations remains a hot topic for international debate. Brain-dead organ donors (DBDs) constitute the majority of organ donations in Poland.

Objectives: To identify the factors that guided intensivists in qualifying a brain-dead patient as a potential organ donor, and whether the factors that significantly influenced the decision to qualify constituted an actual contraindication.

Material and methods: We performed a retrospective study based on data from the Silesian ICU Registry from 2010-2020 and publicly available information from Poltransplant. We compared the demographic and clinical characteristics of patients diagnosed with brain death who were identified as eligible and ineligible organ donors.

Results: Out of 25,465 patients enrolled in the Silesian ICU Registry, brain death was diagnosed in 385 (1.51%) study participants, and 61 of the records were excluded due to data incompleteness. In the remaining group (n = 324), there were 201 men and 123 women. Of them, only 180 study participants were reported as eligible donors (55.5%). Six patients had absolute contraindications to organ donation.

Conclusions: A relatively small number of patients diagnosed with brain death were qualified by intensivists as eligible organ donors, with a limited number of medical factors influencing this decision. This means that other non-medical factors may affect the qualification of DBDs for organ procurement.

Mental health diagnostics is undergoing a transformation, with a shift away from traditional categorical systems like the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and the International Classification of Diseases, 11th Revision (ICD-11), and toward innovative frameworks like the Hierarchical Taxonomy of Psychopathology (HiTOP) and the Research Domain Criteria (RDoC). These emerging models prioritize dimensional and biobehavioral approaches in order to overcome limitations such as oversimplification, comorbidity and heterogeneity. This editorial explores the challenges of implementing these paradigms, such as the need for empirical validation, interdisciplinary collaboration and clinician training. It highlights the importance of advanced tools, biomarkers and technological integration to improve precision in diagnosis and treatment. Future research directions include creating reliable dimensional assessment methods, conducting longitudinal studies and fostering interdisciplinary networks. By bridging traditional and emerging frameworks, the field can progress toward personalized, biologically informed mental health treatment. This transition necessitates collaboration among researchers, clinicians and policymakers to improve diagnostic accuracy and treatment outcomes for those affected by mental health disorders.

Background: Previous research has shown that moral judgments are affected by social cognitive abilities, such as theory of mind (ToM). This study examines how information about an actor's beliefs and the consequences of their actions affect the moral evaluation of the character's behavior in social events. Our research builds upon previous studies, which have shown that these factors contribute differently to moral judgments made by both adults and young children.

Objectives: This study aimed to explore how participants with schizophrenia and healthy controls read stories about social situations in the context of moral judgments.

Material and methods: The study used the research procedure that included 4 variants of 16 scenarios describing social situations, and thus comprising 64 stories. After each story, participants evaluated their confidence level on a 4-point scale. To assess delusional beliefs, the Polish adaptation of the Peters Delusion Inventory (PDI) questionnaire and the Paranoia Checklist (PCh) were used. Respondents completed these questionnaires after completing the scenario test procedure.

Results: In social situations, patients with paranoid schizophrenia were found to evaluate actions of protagonists who attempted to harm another person more leniently than when it was an accident. Conversely, healthy individuals judged those actors who expressed intentions to hurt another person significantly more harshly than in an accident situation. Metacognition measures show that paranoid schizophrenia patients make moral judgments with high confidence, despite being based on an incorrect reading of the other person's intentions.

Conclusions: The study indicates that ToM has a significant impact on the moral judgment of others. Decreased moral cognition can result from both positive and negative symptoms. Deficits related to metacognition can also sustain such cognitive distortions.

Background: Osteoporosis is a metabolic disease characterized by increased bone fragility. As it is characterized as a general skeletal disease, changes can also be seen in the stomatognathic system (edentulism, wrong fitting of dentures, etc.). The question is whether early changes in the salivary mineral content and acid-base balance may reflect skeletal status and risk of bone fracture.

Objectives: The objective of the study was to evaluate whether minerals in the saliva were associated with skeletal fractures in a population of postmenopausal women.

Material and methods: In this observational study, dental examinations along with the collection of saliva were conducted in 117 randomly recruited women (mean age 64.6 ±5.9 years). The study group included 23 study participants with fractures, of which 10 had a history of osteoporotic fractures. Saliva samples for mineral content including copper (Cu), zinc (Zn), calcium (Ca), and phosphorus (P), as well as salivary pH were collected and analyzed to determine associations between salivary mineral content and fracture risk.

Results: As a result, the median pH value was 6.8, and the median levels for Cu (0.35 μmol/L), Zn (0.61 μmol/L), Ca (0.7 mmol/L), and P (6.64 mmol/L) were observed. No differences were noted in salivary mineral content and acid-basic balance between the fractured and non-fractured participants.

Conclusions: The results of our study suggest that salivary mineral content has limited usability in predicting skeletal fragility in postmenopausal women when used alone.