Advances in Clinical and Experimental Medicine最新文献

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.

Perinatal mental health has been increasingly recognized as one of the most prevalent and consequential complications of pregnancy and childbirth. Approximately 1 in 5 women experience depression during or after pregnancy, and up to 1 in 4 encounter difficulties in establishing an emotional bond with their infants - a condition known as mother-to-infant bonding difficulties (MIBD). Pooled global estimates from meta-analyses indicate that these conditions are more prevalent than major obstetric complications such as gestational diabetes and preeclampsia. They also represent the leading cause of maternal mortality, particularly in high-income countries. For example, suicidal ideation (SI) is approx. 16 times more common among women with postpartum depression (PPD) than among those without. Moreover, SI occurring alongside PPD is often associated with prior depressive episodes and a lack of social support, whereas SI in the absence of depression tends to be linked to first-time motherhood, infection during pregnancy, or loneliness. Postpartum depression and MIBD are also closely interconnected, exhibiting a bidirectional relationship and sharing major risk factors such as prenatal depression, limited family support, and adverse childhood experiences. When left untreated, perinatal depression and MIBD can impair maternal functioning and delay infants' emotional, cognitive and social development. Emerging integrative approaches that combine psychotherapy with bonding-focused, lifestyle and psychosocial components show promise in improving outcomes. Future research should focus on developing comprehensive, multimodal interventions that integrate psychotherapy with lifestyle and psychosocial elements within a preventive, family-centered framework, promoting sustained recovery beyond active treatment.

Background: Many studies reported positive effects of physical exercise on the condition of dialysis patients. The insufficient value of those changes makes it difficult to interpret their clinical relevance.

Objectives: This study aimed to assess the influence of selected training (endurance, resistance, tai chi) on cardiopulmonary fitness and muscle function, as well as to analyze the factors having the most significant effect on cardiopulmonary fitness in a group of dialysis patients.

Material and methods: Ninety-eight patients agreed to participate in the study. Selection of the type of training was done by cluster randomization. Group 1 were patients in a cluster with an endurance exercise program, and group 2 in a cluster with resistance exercises. Group 3 consisted of patients who took part in a tai chi program (non-cluster randomization). Exercise programs with each of the 3 groups were conducted for a period of 6 months, 3 times a week (groups 1 and 2) and twice a week (group 3), up to 60 min for 1 session.

Results: The full exercises was completed by 45 patients: group 1 - 16; group 2 - 15; group 3 - 14. The significance of the observed difference in the cardiopulmonary function was confirmed only in endurance group for absolute oxygen concumption (VO2) and heart rate (HR). Measurements of peak torque (PTQ) and total work (TW) performed at a speed of 60°/s showed a significant increase in the measured values only in the resistance training group. Measurements of PTQ and TW performed at 180°/s showed a significant increase in the measured values in the endurance and resistance group.

Conclusions: The 6 months of training resulted in a slight improvement in cardiopulmonary parameters only in the endurance group. The above results seem to confirm the observed limited potential for improving aerobic capacity in dialysis patients. The results of strength and speed parameters shows the specificity of each training, expressed by selective improvements in isometric and both isokinetic tests.

Background: Despite legal advances and the depathologization of transgender identities, transgender individuals still face significant barriers and discrimination within healthcare systems. A pervasive lack of training in gender diversity among healthcare professionals often results in uncomfortable, even hostile, clinical encounters, exacerbating physical and mental health vulnerabilities. Consequently, fear of stigma and discrimination leads many transgender people to avoid seeking care, placing their wellbeing at further risk due to delayed or foregone medical attention.

Objectives: To explore transgender individuals' perceptions of healthcare professionals' awareness and responsiveness to their care and support needs in the Valencian Community (Spain).

Material and methods: We conducted a descriptive qualitative study with a phenomenological approach in the Valencian Community. Using convenience sampling, we recruited 14 participants. Data were collected between April and June 2022 via in-depth, semi-structured, open-ended interviews. The study comprised 2 sequential phases: An initial focus group session, followed by individual interviews conducted using a snowball sampling technique.

Results: We identified 3 thematic domains: T1: Experiences of professional care among transgender individuals; T2: Impact of cisgender-centric regulations within the healthcare system; T3: Gender diversity education needs for healthcare professionals.

Conclusions: The transformation of the health system is urgent to ensure inclusive and equitable care for transgender people. According to the interviews, they consider that better training of professionals will improve their care. In addition, they highlight the need to reduce bureaucratic barriers, create specific protocols, and improve access to specialized treatment. Implementing inclusive public policies will contribute to a fairer and more accessible system.

Background: Stroke is a leading cause of disability and one of the primary causes of death worldwide. Stroke survivors often experience a range of symptoms, including impaired motor function, speech and language abnormalities, swallowing difficulties, cognitive deficits, visual disturbances, and sensory impairments.

Objectives: This meta-analysis was conducted to assess and compare the relative effectiveness of telerehabilitation compared to traditional in-person speech and language therapy for individuals with aphasia.

Material and methods: A comprehensive literature search was conducted up to October 2024, reviewing 1,185 identified studies. Ultimately, 6 studies were selected that included a total of 168 participants with aphasia at baseline. The meta-analysis examined the relative effectiveness of telerehabilitation compared to traditional in-person speech and language therapy using continuous outcomes, with mean differences (MD) and 95% confidence intervals (95% CIs) calculated. Analyses were performed using either fixed-effect or random-effects models, depending on heterogeneity.

Results: In individuals with aphasia, telerehabilitation demonstrated significantly greater improvements in generalization post-intervention compared to face-to-face treatment (MD = 11.53; 95% CI: 3.64-19.43; p = 0.004). However, no significant differences were found between telerehabilitation and face-to-face treatment in naming accuracy post-intervention (MD = 3.09; 95% CI: 1.98-8.16; p = 0.23), Western Aphasia Battery (WAB) aphasia quotient (MD = -0.54; 95% CI: -9.96-8.88; p = 0.91), auditory comprehension post-intervention (MD = 0.66; 95% CI: -8.83-10.14; p = 0.89), or functional communication post-intervention (MD = -0.95; 95% CI: -10.19-8.29; p = 0.84).

Conclusion: In individuals with aphasia, telerehabilitation showed significantly greater improvements in generalization post-intervention compared to face-to-face treatment. However, no significant differences were observed between the 2 approaches in naming accuracy, WAB aphasia quotient, auditory comprehension, or functional communication post-intervention. To validate these findings, further research is needed, and caution should be exercised when interpreting the current results due to the limited number of included studies.

Minimally invasive techniques are progressively transforming colorectal (CRC) surgery. Given the high mortality and morbidity rates associated with conventional surgical treatments for CRC, the development of less invasive alternatives is crucial. The long-established use of transanal platforms for local excision of early-stage rectal cancers paved the way for the development of a transanal approach to total mesorectal excision (TME). Transanal total mesorectal excision (taTME) has emerged as a novel technique for treating low CRC, offering superior and more accurate visualization of the presacral mesorectal plane compared to the abdominal approach, and providing particular advantages in the narrow male pelvis. The current data on oncological and functional outcomes are promising. The transanal transection and single-stapled anastomosis (TTSS) approach represents the latest advancement in transanal techniques for treating low CRC. Evolving from taTME, it provides a more controlled and potentially safer anastomotic technique. However, the data are still preliminary, and larger studies are needed to validate its effectiveness. This review explores the evolution of minimally invasive and transanal surgical techniques for low CRC treatment, comparing outcomes across various approaches with a focus on patient selection criteria and oncological results.

Background: Despite the broad range of treatment options available for intestinal inflammation, the development of novel therapeutics remains essential due to the diminishing effectiveness of current therapies over time. Both the endocannabinoid system (ECS) and nociceptin/orphanin FQ peptide (NOP) receptors have been implicated in the pathogenesis of diseases associated with intestinal inflammation, highlighting their potential as therapeutic targets.

Objectives: We hypothesized that an interaction exists between cannabinoid receptors 1 and 2 (CB1 and CB2) and the NOP receptor, which may hold therapeutic relevance for the treatment of colitis.

Material and methods: In this study, we used 3 selective ligands: a CB1 antagonist (AM6545), a CB2 antagonist (AM630) and a NOP agonist (SCH221510) in a mouse model of colitis induced by 3% dextran sulfate sodium (DSS). Quantification of several secondary messengers was conducted using western blot analysis. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess CB1 expression levels in colonic tissue, while liquid chromatography-mass spectrometry (LC-MS) was used to evaluate the concentrations of endocannabinoids and related lipid mediators.

Results: We observed a statistically significant increase in the macroscopic score and a nonsignificant increase in the microscopic score in inflamed mice treated with both AM6545 and SCH221510 compared to those treated with SCH221510 alone. Additionally, the combination-treated group exhibited significantly lower levels of extracellular signal-regulated kinases 1/2 (ERK1/2) and significantly higher levels of phosphorylated protein kinase B (p-AKT) and β-arrestin relative to the SCH221510-only group.

Conclusions: Our study offers novel insights into the interaction between the ECS and the NOP receptor, which may inform the development of new therapeutic strategies for inflammatory conditions such as colitis.

Cardiovascular prevention guidelines are based on robust evidence, yet their implementation in primary healthcare remains inconsistent due to systemic barriers, workload pressures and insufficiently adapted tools. The 2025 European consensus emphasizes the need for multidisciplinary teamwork, digital innovation and equity-focused strategies to strengthen prevention across diverse healthcare systems. Translating these recommendations into actionable, context-specific approaches is essential to close the evidence-practice gap and improve population cardiovascular outcomes.