Advances in Clinical and Experimental Medicine最新文献

Background: Breast cancer (BC) is now the most common malignancy in women. Early detection and precise diagnosis are essential for improving survival.

Objectives: To develop an integrated computer-aided diagnosis (CAD) system that automatically detects, segments and classifies lesions in mammographic images, thereby aiding BC diagnosis.

Material and methods: We adopted YOLOv5 as the object-detection backbone and used the Curated Breast Imaging Subset of the Digital Database for Screening Mammography (CBIS-DDSM). Data augmentation (random rotations, crops and flips) increased the dataset to 5,801 images, which were randomly split into training, validation and test sets (7 : 2 : 1). Lesion-classification performance was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC), precision, recall, and mean average precision at a 0.5 confidence threshold (mAP@0.5).

Results: The CAD system yielded an mAP@0.5 of 0.417 and an F1-score of 0.46 for lesion detection, achieved an AUC of 0.90 for distinguishing benign from malignant lesions, and processed images at 65 fps.

Conclusions: The integrated CAD system combines rapid detection and classification with high accuracy, underscoring its strong clinical value.

Background: Amiodarone is the most commonly used class III antiarrhytmic drug with antiarrhytmic and vasodilator properties. Adenosine triphosphate (ATP) serves as a crucial source of intracellular energy, while resveratrol is known for its potent antioxidant activity.

Objectives: This study aimed to biochemically, histopathologically and immunohistochemically evaluate the effects of ATP, resveratrol and their combination on potential liver damage and dysfunction induced by amiodarone in rats.

Material and methods: The rats were divided into 6 groups: healthy control (HG), amiodarone alone (ADG), amiodarone + ATP at 2 mg/kg (AAG-2), amiodarone + ATP at 5 mg/kg (AAG-5), resveratrol + amiodarone (RAG), and resveratrol + amiodarone + ATP at 2 mg/kg (RAA-2). Amiodarone (50 mg/kg, orally), ATP (2 mg/kg and 5 mg/kg, intraperitoneally) and resveratrol (25 mg/kg, orally) were administered once daily for 14 days. Following treatment, liver tissues were excised for biochemical analysis. Oxidative stress was assessed by measuring malondialdehyde (MDA) levels, while antioxidant status was evaluated through total glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. To assess liver function, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in serum samples collected from the animals' tail veins. In addition, liver tissues were subjected to histopathological and immunohistochemical examination to evaluate structural and molecular changes associated with treatment.

Results: Amiodarone administration led to a significant increase in oxidative stress markers and a reduction in antioxidant levels in rat liver tissue. Additionally, serum levels of ALT and AST were elevated, indicating liver dysfunction. Histopathological and immunohistochemical analyses revealed severe (grade 3) oxidative damage in the liver tissue. All biochemical parameters in the 5 mg/kg ATP and resveratrol + 2 mg/kg ATP treatment groups were comparable to those observed in the HG group. Histopathological and immunohistochemical evaluations showed a reduction in liver damage severity to grade 2 in the groups treated with ATP (2 mg/kg) and resveratrol alone, and to grade 1 in the groups receiving ATP (5 mg/kg) or the combination of resveratrol + ATP (2 mg/kg).

Conclusions: The results of the present study suggest that adjusting the ATP dosage or using a combination of ATP and resveratrol may be effective strategies for minimizing amiodarone-induced liver damage.

Background: Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide and claims roughly 700,000 lives each year; nearly 50% of global HCC fatalities occur in China.

Objectives: To conduct a comprehensive meta-analysis identifying predictors of sorafenib efficacy in combination with thermal ablation for HCC treatment.

Material and methods: A comprehensive literature search was conducted up to October 2024, reviewing 720 identified studies. From these, 19 studies were selected that included a total of 3,341 participants with HCC at baseline. The meta-analysis examined the effects of sorafenib in combination with physical thermal ablation, using odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses were performed using two-sided methods and either fixed-effect or random-effects models, depending on the level of heterogeneity.

Results: The meta-analysis revealed that combining physical thermal ablation with sorafenib significantly improved outcomes in HCC patients: Overall survival (OS) was more than doubled (OR = 2.03; 95% CI: 1.55-2.67; p < 0.001), recurrence rates were significantly reduced (OR = 0.62; 95% CI: 0.39-0.98; p = 0.04), and overall treatment efficacy was markedly higher (OR = 2.53; 95% CI: 1.61-3.96; p < 0.001) compared with thermal ablation alone.

Conclusion: In individuals with HCC, physical thermal ablation and sorafenib had significantly higher OS, lower recurrence rates, and high overall efficacy compared to physical thermal ablation. To validate this discovery, more research is needed, and caution must be implemented when interacting with its values.

Disasters, wars and health emergencies profoundly affect mental health, with nearly 1/3 of affected populations developing conditions such as posttraumatic stress disorder (PTSD), depression or anxiety, particularly among vulnerable groups like children, the elderly and the chronically ill. Access to mental health and psychosocial support (MHPSS) is often limited by conflict-related disruptions, stigma or resource shortages, while healthcare workers themselves face immense psychological strain and inadequate protection. Long-term strategies integrating disaster preparedness, mental health services and professional support are essential to safeguard both affected populations and frontline workers during emergencies.

Today, it is well established that the tumor microenvironment (TME), the tumor niche, along with melanoma cells, plays a crucial role in cancer dissemination and influences the effectiveness of anticancer therapies. Therefore, it may serve as a potential therapeutic target in melanoma treatment. In our research, we focused on the effects exerted by cells within the melanoma microenvironment on cancer progression and the development of therapy resistance. Specifically, we examined stromal cells accompanying melanoma cells in the tumor - cancer-associated fibroblasts (CAFs), cancer-associated keratinocytes (CAKs), and cancer-associated adipocytes (CAAs). Particular attention was given to keratinocytes, as their role in the melanoma microenvironment remains the least understood.

Background: Healthcare systems can present unique challenges for individuals in the lesbian, gay, bisexual, and transgender (LGBT) community, often making it difficult for them to access suitable and respectful care.

Objectives: The aim of this study was to perform a transcultural adaptations and to evaluate psychometric properties of the Spanish version of the Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale (LGBT-DOCSS-ES). This adaptation is intended for application within Spanish-speaking healthcare settings.

Material and methods: The LGBT-DOCSS was translated and adapted from the original English version into Spanish using a standardized process, including forward translation, back-translation, and expert panel review. Psychometric properties were tested on a sample of 270 participants from Spain. Internal consistency was evaluated using confirmatory factor analysis (CFA), Cronbach's alpha, the discriminative power index, and McDonald's omega (ω).

Results: The study included 270 participants, with 58.9% being female and 38.9% male. Of the respondents, 52.2% identified as heterosexual, 32.6% as homosexual and 13% as bisexual. The internal consistency of the Spanish version and its domains was good with an overall Cronbach's alpha of 0.746. The alpha ranges for each subscale domains were between 0.769 and 0.822. The McDonald's ω coefficient was 0.808.

Conclusions: The Spanish version of the LGBT-DOCSS-ES has good properties of factorial validity. This tool is a valuable resource for assessing cultural competence and clinical skills among healthcare providers in Spanish-speaking settings.

Background: Porphyromonas gingivalis is a major human oral opportunistic pathogen and a key etiological agent of periodontal disease, contributing to inflammation and bone loss in the oral cavity. Periodontitis is not limited to oral health complications; it has also been associated with a range of systemic conditions, including coronary heart disease (CAD), respiratory disease, rheumatoid arthritis, chronic kidney disease (CKD), and certain types of cancer.

Objectives: Immunization-based prevention of periodontitis appears to be a promising strategy; however, no vaccine is currently available for commercial use. In the present study, a novel vaccine candidate against P. gingivalis was proposed, consisting of a P. gingivalis protein, gingipain, glycosylated with the carbohydrate moiety of P. gingivalis lipopolysaccharide (LPS).

Material and methods: Glycosylation of gingipain was achieved in Escherichia coli by introducing the Campylobacter jejuni N-glycosylation system, the P. gingivalis LPS biosynthetic pathway and the gingipain gene.

Results: The neoglycoprotein was purified using column chromatography to a purity exceeding 99%, yielding a soluble antigen. The modified protein was recognized by commercial antibodies targeting the protein backbone, the carbohydrate moiety, and a custom monoclonal antibody specific to the purified LPS of P. gingivalis American Type Culture Collection (ATCC) 33277. The glycoprotein was used to immunize mice, and the resulting sera were analyzed for their ability to opsonize bacterial cells. The absence of detectable opsonization suggests that the elicited antibodies are more likely directed against the protein component of the vaccine rather than the glycan surface antigen.

Conclusions: The final product was most likely assembled correctly, as it was recognized by LPS-specific antibodies. Further evaluation in an animal model of induced periodontitis is necessary to determine whether the elicited antibodies can effectively inhibit gingipain released by the pathogen. If this vaccine candidate demonstrates protective efficacy, the approach could accelerate and enhance the safety of vaccine design against a wide range of other pathogens.

Background: A group of inflammatory spindle cell lesions (ISCLs) includes many nosological entities with a common histological image consisting of spindle-shaped cells and inflammatory infiltrate. Diverse diseases indicate different prognoses that can be difficult to predict. The most well-known neoplasm from the group is an inflammatory myofibroblastic tumor (IMT) that harbors tyrosine kinase gene rearrangement frequently affecting ALK, ROS1, RET, PDGFRB, NTRK, and IGF1R genes. In contrast, a reactive mass-forming lesion is regarded as an inflammatory pseudotumor (IPT).

Objectives: This study aimed to: 1) investigate the accuracy of the primary diagnosis of IMT and IPT with the diagnostics using extended analysis of clinical data, re-evaluation of histopathological slides and next-generation sequencing (NGS); and 2) to establish prognostic and diagnostic factors.

Material and methods: Finally, 46 cases of ISCLs were retrieved. The authors revised diagnoses and performed NGS based on ribonucleic acids isolated from selected paraffin blocks. Clinical and paraclinical data were also collected. The final diagnoses were made as a result of available information integration.

Results: The sequencing confirmed 4 IMTs and detected 4 fusion gene types - EML4-ALK, RANBP2-ALK, and ETV6-NTRK3. Additionally, 1 afunctional EGFR-PPARGC1A rearrangement was found in gastric inflammatory fibroid polyp. A subset of reactive lesions also contained some mutations, which is consistent with actual knowledge. Neoplasms with ganglion-like cells, nuclear atypia and increased mitotic activity gave local recurrences. A higher percentage of necrosis indicated IMTs and patients who died in the analyzed period. No relation between genetic alterations and relapse was found.

Conclusions: A final diagnosis can be made based on all clinical and paraclinical data. The prognosis after the treatment is dependent on the pathological diagnosis, disease location and resection completeness, presence of ganglion-like cells, nuclear atypia, mitotic index, and necrosis. Not only neoplastic but also reactive lesions can recur. The presence of gene rearrangements and necrosis can have diagnostic value.

Background: Polycystic ovary syndrome (PCOS) is a complicated endocrinological disorder.

Objectives: We investigated the ferroptosis-regulated role of MALAT1 and its potential modulatory mechanisms in granulosa cells (GCs).

Material and methods: Reverse transcripton quantitative polymerase chain reaction (RT-qPCR) was used to measure the relative expression of MALAT1/miR-155-5p/PAK2 in KGN cells after transfection. Online bioinformatic analysis was performed to predict the interactions between MALAT1/PAK2 and miR-155-5p. Dual luciferase assays were performed for relative luciferase activity in cell groups co-transfected with the pmiRGLO plasmids containing wild type (wt) or mutant type (mt) of MALAT1 (MALAT1-wt, MALAT1-mt), siRNA targeting MALAT1(si-MALAT1) miR-155-5p inhibitor or their control was transfected into KGN cells using Lipofectamine 2000. After 48 h, the transfected cells were collected for the following experiments. Cell viability and apoptosis were measured using Cell Counting Kit-8 (CCK-8) and flow cytometry. Malondialdehyde (MDA) level and reduced glutathione (GSH) / oxidized glutathione disulfide (GSSG) ratio were detected using commercial kits. Western blot was used to measure the relative protein changes in PAK2, SLC7A11 and GPX4.

Results: Knockdown of MALAT1 decreased cell viability, increased apoptosis and ferroptosis, which was reversed by miR-155-5p inhibition. MALAT1 downregulation inhibited PAK2, while miR-155-5p inhibition activated PAK2. The increase of relative luciferase activity in cells transfected with MALAT1-wt or PAK2-wt and miR-155-5p inhibitor suggests the bindings between miR-155-5p and MALAT1 or PAK2.

Conclusions: This study revealed a novel ferroptosis-modulated role of MALAT1 in PCOS in vitro via interactions with miR-155-5p/PAK2. Further in vivo and clinical studies are needed to validate these in vitro findings and fully assess the therapeutic potential of MALAT1 in PCOS.

Background: The chronic progression of viral hepatitis and the terminal stage of cirrhosis impose a long-term disease burden on patients. The assessment of liver damage can be facilitated through the measurement of liver biomarkers.

Objectives: To conduct a comprehensive analysis of the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), liver biomarkers, and cirrhosis via Mendelian randomization (MR).

Material and methods: A bidirectional multi-sample MR approach was used to extract data from publicly available genome-wide association studies (GWAS) databases. Information on liver biomarkers and cirrhosis, along with data from 351,885 HBV samples containing 19,079,722 single nucleotide polymorphisms (SNPs) and 176,698 HCV samples comprising 12,454,320 SNPs, were aggregated. The TwoSampleMR 0.5.7 package in R language facilitated the bidirectional MR analysis, utilizing methods such as inverse-variance weighting, weighted median and MR-Egger to investigate the causal relationships between HBV, HCV, liver biomarkers, and cirrhosis.

Results: The MR analysis revealed potential causal relationships between cirrhosis and HBV infection, indicating an increased probability of HBV as cirrhosis escalates (odds ratio (OR) = 1.253; 95% confidence interval (95% CI): 1.037-1.514; p = 0.019). Additionally, a potential causal link was observed between HBV and the level of aspartate aminotransferase (AST), with an increase in HBV leading to a gradual decrease in AST levels (OR = 0.972; 95% CI: 0.958-0.986; p < 0.01). A similar causal relationship was identified between HCV infection and cirrhosis, where the probability of cirrhosis significantly increases with rising HCV levels (OR = 2.213; 95% CI: 1.752-2.796; p < 0.01). The results demonstrated no pleiotropy or heterogeneity within the analysis.

Conclusions: This research highlights a causal relationship between HBV and AST levels, suggesting that monitoring AST levels can indicate the extent of liver damage caused by chronic HBV infection. Additionally, causal connections were established between HBV, HCV and cirrhosis, emphasizing that cirrhosis represents the terminal stage of chronic HBV and HCV infections. By managing the progression of the disease, the risk of cirrhosis can be reduced.