Biomedical Papers

The role of DNA methylation in the regulation of HLA expression

Adam Strnad, Martin Petrek — 2026-09-23 00:00:00

This review provides a thorough overview of how allele-specific DNA methylation influences immune responses by regulating gene expression within the immune system's primary regulatory complex. It emphasises the role of specific CpG-SNP interactions and epigenetic alterations in modulating susceptibility to autoimmune diseases. By linking molecular mechanisms to clinical relevance, the manuscript provides new insights into the epigenetic regulation of antigen presentation and immune tolerance. It also explores potential opportunities for discovering biomarkers and developing targeted therapeutic strategies.

Structure, function and usage of integrin alpha 6 (CD49f): A comprehensive review

2026-09-23 00:00:00

Integrin α6 (CD49f, ITGA6) is a laminin-binding adhesion receptor with essential roles in stem cell biology and cancer progression. This review synthesizes current knowledge on α6ITG isoforms, ligand interactions, downstream signaling pathways, and its context-dependent expression in both healthy and pathological tissues. Special attention is given to its expression in cancer stem cells and its potential as a prognostic or therapeutic target.

Mini review on the laboratory diagnosis of amyloidosis: An overview of methods, applications, and trends in analytical approaches

2026-09-23 00:00:00

This review summarizes key analytical strategies for detecting misfolded fibrillar deposits using three complementary approaches: tissue-based staining and immunolabeling, separation techniques, and proteomics. Mass spectrometry stands out for its precision in subtype identification. Together, these methods form a structured diagnostic framework that enables earlier recognition, supports individualized treatment, and improves outcomes in complex protein deposition disorders.

Serum vitamin D levels in patients with lung metastases

2026-09-23 00:00:00

This study investigates the relevance of serum vitamin D3 levels in patients with a history of malignancy, with particular focus on those with confirmed lung metastases. Among 38 patients, seasonal variations showed significantly higher vitamin D3 levels in summer. No significant difference in vitamin D3 levels was found between patients with or without lung metastases. However, in winter, patients with a history of multiple malignancies had notably lower vitamin D3 levels than those with a single malignancy. These findings suggest that vitamin D supplementation, particularly in winter, may be beneficial for certain subgroups, warranting further investigation in larger cohorts.

Serum drug levels and medication adherence in heart failure: A comparative cohort analysis

2026-09-23 00:00:00

Medication adherence is essential for effective heart failure management, yet non-adherence remains a significant concern. This study, part of the LEVEL-CHF Extended Registry, analysed adherence using serum drug level testing in cohorts from 2018 and 2020. While most patients adhered to treatment, adherence declined in 2020. Despite this, clinical differences between adherent and non-adherent patients were minimal. The study underscores the importance of direct adherence measurement and suggests that serum drug level testing could enhance heart failure treatment strategies, guiding personalized interventions.

Potential of silymarin and its polyphenols to affect Nrf2 signalling pathway in human skin cells

2026-09-23 00:00:00

Silymarin, a well-known hepatoprotective agent, has become the focus of dermal application. Minimal knowledge exists about its effect on transcriptional nuclear factor erythroid 2-related factor 2 (Nrf2). However, evidence for severe adverse effects of prolonged Nrf2 activation in skin is accumulating, predominantly keratinocyte hyperproliferation and impaired skin barrier function. This study showed no significant effect of silymarin or its components on the studied Nrf2 regulating proteins or Nrf2-driven genes.

The relationship of the systemic immune inflammation index to severity in chronic spontaneous urticaria

2026-09-23 00:00:00

This article is an investigation of the association between the severity of chronic spontaneous urticaria (CSU) evaluated using the Urticaria Activity Score-7 (UAS-7) and its relation to the systemic immune inflammation index (SII). The SII, a simply available and objective inflammatory marker has a good correlation with UAS-7, and may be used as an addition to the UAS-7 in the treatment CSU. The SII may be a useful tool in the evaluation and management of CSU.

Comparing the efficiency of two prophylactic approaches in patients at risk of developing Intraoperative Floppy Iris Syndrome

2026-09-23 00:00:00

Intraoperative Floppy Iris Syndrome (IFIS) is a condition that can potentially lead to serious complications during cataract surgery that threaten the patient's final vision. There are a number of guidelines for operative technique modifications with the aim of preventing the development of IFIS. This study focuses on two options for prophylactic strategies: the application of atropine drops and the instillation of intracameral epinephrine. Epinephrine clearly leads to a reduced number of mild forms of IFIS, however it is not sufficiently effective in severe forms of IFIS, where atropine was more effective. The authors confirm that IFIS is difficult to predict and that there is still no clear recommendation that would prevent the development of IFIS in all high-risk patients.

A case-control study of promoter and 5'UTR VEGF polymorphisms in diabetic retinopathy

2026-09-23 00:00:00

As a complication of diabetes, retinopathy is a major cause of blindness in diabetic patients worldwide. Vascular endothelial growth factor (VEGF) plays a key role in mediating angiogenesis in the retina, which is characteristic of diabetic retinopathy (DR). A potential significant role of VEGF in the development of DR is highly anticipated, and hence we investigated multiple polymorphisms in the promoter and 3'-untranslated regions. The distribution of these polymorphisms was significantly different in diabetic patients versus controls, and in diabetic patients with DR versus without DR. Multiple haplotypes were significantly increased in diabetes mellitus (DM) patients, while some were more common in DR patients. These results emphasize the potential effect of VEGF on DR risk. More mechanistic studies should follow to investigate this role.

Thoracic duct stenting as a treatment for chylothorax and chylous ascites in patient with Yellow Nail Syndrome

2026-09-23 00:00:00

Yellow Nail Syndrome is a rare lymphatic disorder for which no curative treatment exists. When conservative management fails, patients with recurrent chylothorax and chylous ascites have few options beyond repeated drainage. The authors describe a case in which retrograde transvenous access to the thoracic duct enabled balloon dilation and stent placement at an ostial stenosis, restoring physiological lymphatic drainage. At six-month follow-up, thoracocentesis was no longer required and nutritional status normalized. To the authors knowledge, this is the first reported use of thoracic duct stenting specifically in a Yellow Nail Syndrome patient, expanding the potential role of interventional radiology in central lymphatic disease.

Independent causal effect of α, β, and γ crystallin on cataract: A Mendelian randomization study

Xin Li, Ling-Li Xu, Jian Cheng, Qi-Di Hu — 2026-07-20 09:09:32

Objective. This study aimed to explore the independent causal relationship between three types of crystallin proteins (α, β, and γ) and risk of cataract, using single nucleotide polymorphisms (SNPs) as instrumental variables for α, β, γ crystallin through Mendelian randomization (MR) analysis. Methods. Genetic instruments associated with α, β, γ crystallin levels and cataract were obtained from the IEU Open GWAS Project (GWAS IDs: prot-a-673, prot-a-674, prot-a-675, and ukb-d-20002_1278). Two-sample MR analyses were conducted using five different MR algorithms containing MR-Egger, inverse variance weighted (IVW), Weighted median, Simple mode, and MR-PRESSO. Results. The MR analysis revealed a significant causal relationship between α crystallin level and the risk of cataract [odds ratio (OR)_IVW= 0.9989, 95% CI 0.9978~0.9999; OR_MR-PRESSO= 0.9988, 95% CI 0.9978~0.9999]. Conversely, no significant causal relationship was found between β or γ crystallin and the risk of cataract. Conclusion. The occurrence of cataract may be potentially linked to abnormal levels of α crystallin, suggesting that monitoring and managing these levels could be crucial in understanding and potentially mitigating the risk of cataract.

The prevalence of increased lipoprotein (a) in the Czech general population and in patients with coronary heart disease

Otto Mayer Jr, Daniel Rajdl, Jan Bruthans, Renata Cifkova, Jan Filipovsky — 2026-07-14 16:09:26

Background. Lipoprotein(a) (Lp(a)) is a cardiovascular risk factor (RF) with potentially high clinical impact. However, in the "real world", it remains largely overlooked, and the epidemiological circumstances of this RF have not yet been systematically studied in the Czech population. The aim of this study was to determine the prevalence of elevated values in cardiovascular patients and in the general population of this country. Methods. A descriptive survey and case-control study were conducted on 2001 subjects [mean age 61.5 years (±SD 12.5); 62.9% males], 1016 cases-patients with manifest coronary heart disease, (CHD), and 985 controls-a random general population sample. Results. The CHD patients had a significantly higher prevalence of increased Lp(a) (≥125 nmol/L) than the control group (25.1 vs 12.9%, P<0.0001). We found a similar relative difference using a lower cut-off, i.e., Lp(a) ≥105 nmol/L (28.9 vs. 14.6%, P<0.0001). In case-control analysis, fully adjusted odds ratio for Lp(a) ≥125 nmol/L was 1.69 (95%CI: 1.13-2.53, P=0.011), while for Lp(a) ≥105 nmol/L, 1.71 (95%CI: 1.16-2.52, P=0.006). Increased Lp(a) was also independent of other conventional RFs, and the only major coincidence we found was elevated LDL cholesterol. Conclusions. This study showed a significantly higher prevalence of Lp(a) in patients with manifest CHD compared to the general population. The systematic screening of this RF and pharmacologic intervention are probably warranted in routine clinical practice.

Successful transcranial motor evoked potentials monitoring under remimazolam-based anaesthesia: Case reports of two patients

Jan Hudec, Tereza Prokopova, Michal Galko, Roman Gal — 2026-07-07 15:08:28

Introduction. Intraoperative neurophysiological monitoring is a standard in surgeries with an increased risk of iatrogenic neurological injury development. The gold standard for this monitoring modality is propofol-based total intravenous anaesthesia (TIVA). Although there seems to be no clinically significant complication for propofol administration in patients with soy, egg, or peanut allergies, a whole range of recommendations still prohibit propofol administration in patients with these allergies. Remimazolam is a new, ultra-short-acting benzodiazepine that can potentially be an alternative in cases of propofol contraindications in need of TIVA. Case reports. We report two cases of a 19-year-old girl and a 17-year-old boy undergoing scoliosis surgery with transcranial motor evoked potentials monitoring (TcMEP). We chose remimazolam-based total intravenous anaesthesia due to the severe peanut and soy allergy, respectively. Total intravenous anaesthesia was maintained with remimazolam at a dose of 1.5-2 mg/kg/h and remifentanil at a dose of 0.5-0.8 µg/kg/min. Depth of anaesthesia was controlled using frontal EEG monitoring. TcMEP remained stable and showed no significant alterations throughout the surgeries. No new neurological deficits were detected after the surgeries. Conclusion. Our results show that remimazolam-based anaesthesia may be a safe alternative to propofol-based anaesthesia for surgeries with an intraoperative neurophysiological monitoring, or patients with propofol contraindications but more data are needed.

Corneal tomography detection of elevated ectasia risk in atopic dermatitis patients with no prior ophthalmologic diagnosis

2026-07-07 14:56:46

Background. To investigate the association between atopic dermatitis (AD) and keratoconus (KC) in atopic dermatitis patients with no prior ophthalmologic diagnosis. Methods. Thirty eyes of 30 patients with moderate to severe AD were included in this pilot study and compared to healthy controls (n=20) and patients with forme fruste KC (n=28). In the AD group, diagnosis of KC was based on clinical signs and corneal topography criteria such as inferior steepening (inferior-superior difference>1.45 D) and elevated maximum keratometry values (>47 D). Subclinical KC was defined by the presence of specific sensitive indices from corneal topography, tomography, or biomechanical assessments. Risk factors analyzed for ectasia development were the onset and severity of AD, sensitization to aeroallergens, systemic therapy, concomitant atopic diseases, eyelid eczema, and total IgE. Results. We identified two manifest KC (6.7%), and six subclinical KC (20%) cases in patients with AD but with no previous diagnosis of KC. No overall differences were found in corneal tomography and biomechanics indices between control and AD patients. However, eye rubbing was not identified as a risk factor for developing ectasia in the AD group. Conclusion. Dermatologists should be aware that patients with moderate or severe AD may have a higher risk for developing corneal ectasia, particularly when eyelid eczema is present. The estimated prevalence of KC in patients with AD appears to be higher than that in the general population but more studies are needed.

Clinical efficacy of combined sacubitril/valsartan and the Chinese herbal preparation, Qili Qiangxin Capsules on reverse cardiac remodeling in patients with heart failure with reduced ejection fraction

Fengyun Chen, Jing Gu — 2026-06-15 14:31:03

Background. Heart failure with reduced ejection fraction (HFrEF) is mainly characterized by cardiac remodeling. Sacubitril/valsartan and Qili Qiangxin Capsules (QLQX a Chinese patent medicine, commonly used for the treatment of CHF with wide acceptance in Chinese patients), each benefit HFrEF alone, however, further high-quality clinical evidence is needed to confirm their combined effect on reversing cardiac remodeling. Objective. To study the role of sacubitril/valsartan plus QLQX in reversing cardiac remodeling in HFrEF patients, and provide evidence for optimizing HFrEF treatment. Methods. 124 HFrEF patients were admitted to our hospital from Feb 2023 to Apr 2025. After exclusions, 118 were analyzed and divided by treatment (per electronic records) into two groups: sacubitril/valsartan (58 cases) and sacubitril/valsartan + QLQX (combined group, 60 cases). Primary outcomes included left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular global longitudinal strain (GLS), and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Secondary outcomes included serum cardiac troponin I (cTnI), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), clinical efficacy, 6-minute walking test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ), and adverse events. Results. The combined group showed significantly greater improvements in LVEF and absolute GLS (all P<0.001), greater reductions in LVEDD (P=0.026), LVESD (P=0.039) and NT-proBNP (P=0.020) than the monotherapy group. The combined group had greater reductions in CRP (P=0.003), TNF-α (P<0.001) and cTnI (P<0.001), a higher total clinical effective rate (P=0.008), a greater increase in 6MWT (P=0.025) and a greater decrease in MLHFQ score (P<0.001) than the monotherapy group. Adverse event incidence did not differ significantly between groups (P=0.431). Conclusion. Sacubitril/valsartan combined with QLQX effectively improves cardiac structure and function, boosts HFrEF patients' clinical efficacy and quality of life, and is well-tolerated. It offers a reliable option for optimizing HFrEF treatment.

Comparative study of the endometrial microenvironment's immunohistochemical profile in pre-tumour and tumour conditions: endometrial hyperplasia, endometrioid carcinoma, and serous carcinoma

Paata Jorjoliani, Zaza Bokhua, George Burkadze, Shota Kepuladze — 2026-05-06 09:45:10

Background. Endometrial carcinogenesis involves complex interactions between hormonal signaling and the local immune microenvironment. While atypical endometrial hyperplasia is a recognized precursor to carcinoma, the spatial and phenotypic evolution of immune and hormonal markers during progression remains incompletely characterized. Methods. A retrospective cohort of 150 endometrial specimens, including hyperplasia without atypia (n=40), hyperplasia with atypia (n=40), endometrioid carcinoma (n=40), and serous carcinoma (n=30), was analyzed using immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, estrogen receptor (ER), and progesterone receptor (PR). Digital whole-slide imaging and QuPath were applied to quantify immune cell densities in intratumoral and peritumoral compartments. Correlations between immune markers and hormonal receptors were evaluated, and a subgroup of 27 paired hyperplasia-carcinoma cases was analyzed separately. Results. CD3⁺ and CD8⁺ T-cell densities increased progressively from hyperplasia to carcinoma (P<0.001), with hyperplastic lesions demonstrating predominant peritumoral localization consistent with immune exclusion. FOXP3⁺ regulatory T cells were enriched in neoplastic lesions, particularly in ER/PR-positive tumors. CD8⁺ intratumoral and peritumoral densities showed significant inverse correlations with ER and PR expression (both r=-0.76, P<0.001), whereas FOXP3⁺ infiltration correlated positively with ER and PR (r=0.64, P<0.001). M2 CD163⁺ macrophages demonstrated an inverse association with ER (r=-0.49, P<0.01), while M1 CD68⁺/iNOS macrophages showed no statistically significant correlations. In the paired subgroup, higher peritumoral than intratumoral CD8⁺ densities persisted, indicating residual immune exclusion despite malignant transformation. Conclusions. Endometrial neoplastic progression is characterized by a transition from peritumoral immune exclusion in hyperplasia to increased intratumoral immune infiltration in carcinoma, although this shift is not universal. Hormone receptor-positive tumors exhibit enrichment of FOXP3⁺ regulatory T cells and CD163⁺ macrophages, suggesting hormone-linked immune suppression. These findings highlight combined immune-hormonal biomarkers as potential indicators of progression risk and support further investigation of integrated immunomodulatory and hormone-targeted therapeutic strategies.

Spectrum of germline variants in a group of patients with ovarian cancer

2026-05-05 10:04:04

Introduction. Ovarian tumours represent a highly malignant disease that is often diagnosed at an advanced stage and is associated with a poor prognosis. The most common histological type is high-grade serous carcinoma, characterized by significant genomic instability and homologous recombination defects, particularly due to pathogenic variants in the BRCA1 and BRCA2 genes. The introduction of high throughput sequencing methods has enabled the identification of a broader spectrum of predisposing genes and further emphasised the importance of genetic testing for targeted prevention and individualised treatment. Methods. The aim of our study was to determine the frequency of germline mutations in 117 unrelated patients diagnosed with ovarian, tubal, or primary peritoneal cancer. We also assessed epidemiological and tumor pathogenesis data. The patients were examined with the "CZECANCA" gene panel sequenced by next-generation sequencing (NGS) on an Illumina platform. Results. Pathogenic variants were found in 29% of patients, most commonly mutations in the BRCA1 and BRCA2 genes. The median age of patients with high-grade serous ovarian cancer was 61 years. The median age of BRCA1/2-positive women was 54 years, and all had a positive family history of cancer. Conclusion. Identifying carriers of pathogenic variants enables targeted prevention, earlier detection, and personalized therapy. Despite significant advances in treatment, early diagnosis and screening of at-risk individuals remain a major challenge.

Identification of abnormal expression profile of peripheral blood miRNA and its diagnostic value in grading the severity of COPD

Xiaoqing Zhang, Xiujuan Gong, Lianxia Zhang — 2026-05-04 14:56:47

Background. Chronic obstructive pulmonary disease (COPD) is now a major contributor to illness and death on a global scale. Traditional classifications based on pulmonary-function variables like the FEV1 (% predicted), lack sensitivity to early inflammatory changes and disease heterogeneity. In contrast, MiRNAs have emerged as promising biomarkers for respiratory conditions including COPD. The aim of this study was to examine the association between selected MiRNAs and COPD. Methods. A total of 200 COPD patients (GOLD I-IV, n=50 each) and 50 healthy controls were enrolled. Differentially expressed miRNAs were identified from the GEO database and validated by RT-qPCR. Univariate analysis and LASSO regression were used for feature selection. A logistic regression model incorporating selected variables was established for the forecast COPD severity. KEGG pathway enrichment of miR-518b target genes was performed using DAVID. Results. Five miRNAs (miR-216a, miR-518b, miR-106a, miR-1233, and miR-184) were substantially increased in COPD and correlated with disease severity (P<0.001). LASSO regression identified FEV1 (% predicted), DLCO (% predicted), CAT score, miR-518b, and age as key predictors. The combined model showed excellent classification performance (AUC=0.953; sensitivity=92.9%; specificity=81.3%). MiR-518b emerged as a strong independent risk factor (OR=18.91, P=0.003). Gene set enrichment of miR-518b targets pointed to involvement in both the Toll-like receptor and Hippo pathways, implicating its critical roles in inflammation and airway remodeling. Conclusions. MiR-518b is closely associated with COPD severity and may be useful in clinical practice. A model integrating miRNA expression and clinical parameters provides high predictive value for COPD classification and supports precision diagnosis.

The association between C-reactive protein/albumin ratio and coronary collateral circulation in patients with chronic coronary syndromes and chronic total occlusion

2026-04-16 09:37:01

Background. The C-reactive protein-to-albumin ratio (CAR) has recently gained attention as a novel biomarker reflecting both systemic inflammation and nutritional status. Since inflammation plays a critical role in the formation of the coronary collateral circulation (CCC), this study aimed to investigate the association between CAR and the extent of CCC in patients with chronic coronary syndromes (CCS) and chronic total occlusion (CTO). Methods. A total of 123 consecutive patients with CCS and angiographically documented CTO were included. CCC was assessed using the Rentrop classification and patients were divided into two groups: poor CCC (grades 0-1) and good CCC (grades 2-3). Laboratory data including C-reactive protein (CRP), albumin, lipid parameters, renal and liver function tests, glucose, and complete blood count were recorded. CAR was calculated by dividing CRP (mg/L) by albumin (g/dL), and neutrophil-to-lymphocyte ratio (NLR) was also evaluated. Results. Patients with poor CCC had significantly higher CRP, CAR, and NLR levels (P<0.05 for all). In multivariate logistic regression, both CAR (OR=1.200, 95% CI: 1.102-1.394, P<0.001) and NLR were independently associated with poor CCC. ROC analysis showed that CAR had better predictive value (AUC=0.79) than CRP (AUC=0.75, P=0.02) and NLR (AUC=0.67, P=0.03). A CAR cutoff of 2.36 yielded 67% sensitivity and 68% specificity. Conclusion. Elevated CAR is independently associated with impaired CCC in patients with CCS and CTO. CAR may serve as a simple and superior marker over traditional inflammatory indices in assessing collateral vessel development.

Current perspectives on the indications and surveillance of prosthetic arteriovenous grafts for haemodialysis

Julia Jarosciakova, Petr Utikal, Petr Bachleda, Jana Janeckova — 2026-04-09 11:28:12

A prosthetic arteriovenous graft (AVG) represents a type of vascular access for haemodialysis (HD), employing a synthetic conduit that replaces a native vessel and permits repeated cannulation. Due to their associated complications, particularly thrombosis and infection, arteriovenous grafts (AVGs) have long been regarded as a secondary option. Current recommendations advocate an individualized approach to vascular access planning based on patient´s anatomy, life expectancy, anticipated dialysis duration, and personal preferences, leading to a broader and more flexible use of AVGs. Their key advantage is the potential for early initiation of HD, while minimizing the need for central venous catheters. However, a major disadvantage of AVGs is their tendency to develop stenotic lesions, predominantly at the venous anastomosis, which adversely affects graft patency. If left untreated, this may lead to graft thrombosis. Regular evaluation of AVG function is essential for early detection of stenosis and maintenance of graft patency. Despite its widespread use in clinical practice, the role of AVG surveillance in vascular access management remains a subject of considerable debate, as current evidence regarding its effectiveness in preventing thrombosis and prolonging graft patency is inconclusive.

Perioperative outcomes and graft patency in coronary artery bypass grafting (CABG) after no-touch saphenous vein harvesting: A single-center exploratory study

2026-03-25 11:32:22

Background. The no-touch (NT) technique for saphenous vein harvesting aims to preserve vascular integrity and improve graft performance in coronary artery bypass grafting (CABG). However, concerns remain regarding wound healing disorders and local complications at the graft harvest site. Methods. This prospective observational comparative study included 60 consecutive patients undergoing CABG, allocated to conventional saphenous vein harvesting (CONV, n=30) or the NT technique (NT, n=30). Group allocation was based on routine clinical practice and surgeon preference, without formal randomization. The primary outcome was the incidence of wound healing disorders and local complications at the harvest site. Secondary outcomes included perioperative parameters, major adverse cardiovascular events (MACE), and venous graft patency assessed by computed tomography coronary angiography one year after surgery. Results. Operative time and aortic cross-clamp time were comparable between groups. Shorter graft harvesting time was observed in the NT group (35 ± 7.5 min vs. 43 ± 9.1 min; P=0.001), along with significantly reduced perioperative blood loss (15 ± 7 mL vs. 40 ± 12.1 mL; P<0.0001). The incidence of subcutaneous hematoma on postoperative day 7 was significantly lower in the NT group (20% vs. 60%; P=0.003). No statistically significant differences were found between groups in wound infection rates, MACE, or venous graft patency at one-year follow-up. Conclusion. The NT technique for saphenous vein harvesting offers relevant perioperative advantages, including shorter harvesting time, reduced blood loss, and fewer early local complications, without adversely affecting operative time, major adverse cardiac events, wound infection, or one-year graft patency.

Suicide mapping: Case study on Olomouc and Zlín regions in Czech Republic in 2018-2022

2026-03-19 15:06:36

Background and Aims. Suicide represents a major public health issue influenced by a complex interplay of individual, social, and environmental factors. While suicidological research traditionally focuses on psychological and clinical aspects, spatial dimensions of suicidal behavior remain less explored, particularly in Central Europe. This study presents a geospatial analysis of completed suicides in the Olomouc and Zlín Regions of the Czech Republic between 2018 and 2022, using a unique dataset derived from forensic autopsy records. The primary goal was to demonstrate the potential of spatial processing and interdisciplinary collaboration between forensic medicine and geoinformatics in identifying contextual patterns of suicidal behavior. Methods. A dataset of 585 completed suicides was compiled from forensic autopsy reports, including detailed individual-level characteristics and geolocation data. Spatial analyses were conducted using GIS software, integrating additional layers such as land use, demographic and socioeconomic indicators, and quality of life indices. Both point-level and aggregated data (municipality and administrative district levels) were used to explore correlations and spatial variability. Results. The study confirmed known trends - such as male predominance and the role of alcohol - and identified new spatial relationships, including a negative correlation between blood alcohol concentration and latitude, and between age and distance from residence to suicide location. Spatial analyses were conducted at multiple levels of aggregation and combined with selected socioeconomic and environmental indicators, including quality of life, urban-rural context, and foreclosure (enforcement) rates. The results demonstrate that spatial patterns and correlations between suicide rates and area-based characteristics vary depending on the spatial scale of analysis. Conclusion. The findings illustrate the potential of interdisciplinary collaboration between forensic medicine and geoinformatics and provide an exploratory basis for further research and more context-sensitive suicide prevention approaches.

Analysis of the impact of sleep duration and quality on tear‑film in adults with complementary validation of a mobile healthy‑lifestyle application

2026-03-12 09:19:40

Aims. This study aimed to investigate the relationship between sleep parameters and tear film hydration assessed by tear meniscus height (TMH), and to evaluate the usability of a mobile application for remote behavioral and physiological data collection. Methods. Eighteen healthy adults (mean age 29.6 ± 6.4 years) completed five consecutive days of linked measurements combining objective sleep tracking (using Fitbit Charge 4) and slit-lamp imaging of TMH under standardized conditions. Behavioral data on stress, caffeine intake, and smartphone use were collected via a custom mobile application, whose usability was assessed by the System Usability Scale (SUS). Results. Ninety valid daily records were analyzed. TMH correlated positively with total sleep time (r=0.31, P=0.0033), REM sleep duration (r=0.28, P=0.0066), and sleep quality (r=0.32, P=0.0024). Each additional 30 min of REM sleep increased TMH by approximately 0.014 mm. Short sleepers (<6 h) showed significantly lower TMH (0.121 mm) than normal sleepers (≥6 h; 0.153 mm; P=0.0023). Stress and evening smartphone use were associated with reduced sleep quality and lower TMH. The mobile application achieved excellent usability (SUS = 87 ± 6). Conclusions. Our data indicate that sleep duration and architecture play essential roles in maintaining tear film stability. Behavioral habits that impair sleep continuity may thus directly affect ocular surface physiology. The combined use of wearable sensors and mobile self-reporting represents a practical approach to studying the interaction between sleep and ocular physiology.

20-year experience with laparoscopic adrenalectomy at a high-volume center

2026-03-10 09:11:33

Objective. To evaluate transperitoneal laparoscopic adrenalectomies performed at the University Hospital, Olomouc over a period of 20 years. Introduction. Thanks to the increased availability of imaging, the detection of adrenal disease is increasing. Laparoscopic adrenalectomy is now regarded as the gold standard for the treatment of adrenal disease due to its safety and efficacy despite the increasing popularity of robotic-assisted surgery. Methods. Over a period of 20 years, from 2002 to 2021, we retrospectively evaluated a cohort of 405 patients who had undergone laparoscopic adrenalectomy. The indication criteria for laparoscopic adrenalectomy were hormonally active symptomatic tumours (pheochromocytoma, Conn's syndrome, Cushing's syndrome, etc.), symptomatic cysts or myelolipomas, carcinomas, metastatic disabling or incidentalomas, growing at a rate >1 cm or more per year. Data collected focused on sex, age, medical classification, imaging, operative time, side dominance, hormonal activity, complications associated with surgery, length of hospital stay, and histopathologic verification. No patient who had undergone laparoscopic adrenalectomy was excluded from the cohort. Patients in our cohort were not operated by a single surgeon. Results. Women accounted for 52.1% (211) and men 47.9% (194). The mean age was 55.6 years, BMI 28.7, and median ASA score was 2. Preoperative imaging included abdominal CT in 352 (86.9%) patients, abdominal MRI with contrast agent in 8 (2.0%), and PET/CT in 45 (11.1%) patients. More frequent findings were on the right side in 223 (54.39%) patients. Hormonal activity was found in 271 patients (67 %). Hormone overproduction from the right adrenal gland was found in 120 (44.3%) patients, and from the left in 151 (55.7%). Adenoma was the most frequent histological finding, followed by hyperplasia. Conversion to open surgery was due to bleeding in 2 patients. There was no perioperative or postoperative mortality. According to the Clavien-Dindo classification, minor complications (Grade I) occurred in 375 patients (92.6%). Grade II complications were reported in 17 patients (4.2%). Grade III complications were identified in 13 patients (3.2%) due to operative field bleeding; in three cases (0.7%), surgical revision of the adrenalectomy bed was required. Conclusion. Laparoscopic adrenalectomy is a safe surgical method for the management of adrenal disease and our retrospective follow-up confirmed that it remains the gold standard.

Vitamin D modulates the basal secretion of inflammatory cytokines in breast cancer cells: An in-vitro study

Lina Elsalem, Lina Aldarayseh, Nosayba Al-Azzam, Haneen A. Basheer — 2026-01-23 14:04:25

Background. Proinflammatory cytokines are a pivotal factor in cancer initiation and progression. The paracrine and autocrine secretions of such inflammatory cytokines are reported in different cancer types. Recently, C-C motif ligand (CCL) 5 (CCL5), CCL22, granulocyte-colony stimulating factor (G-CSF), and interleukin-1 receptor antagonist (IL-1 RA) have been detected in basal secretions of breast cancer (BC) cells and linked to BC pathogenesis. While Vitamin D has been found to have anti-inflammatory effects, its modulation on cytokine expression is rarely studied in relation to cancer. Aims. In this study, we evaluated whether vitamin D could modulate cytokine basal levels in BC. Materials and Methods. This in vitro study was conducted on BC cell lines, MCF-7 and MDA-MB-231. Cells were treated with vitamin D (10 and 100 nM), and cytokine levels were measured using the Enzyme-Linked Immunosorbent Assay (ELISA). Results. There was a significant reduction in CCL5 total levels in MCF-7 cells at both concentrations (P≤0.01) and in MDA-MB-231 at 100 nM (P≤0.05). Both concentrations reduced CCL22 levels significantly in MCF-7 (P≤0.05) and MDA-MB-231 (P≤0.01). Regarding G-CSF, a significant reduction was found in MCF-7 at both concentrations (P≤0.05) and at 100 nM in MDA-MB-231 (P≤0.01). In comparison, IL-1 RA levels were significantly elevated in MCF-7 (100 nM (P≤0.01)) and MDA-MB-231 (10 nM (P≤0.05) and 100 nM (P≤0.01)). Conclusion. Vitamin D down-regulated the pro-inflammatory and up-regulated the anti-inflammatory cytokines. This indicates that vitamin D can modulate the expression of inflammatory mediators, particularly in a cancer setting. The results support the potential use of vitamin D as an anti-cancer agent with anti-inflammatory properties.

Prognostic significance of L1CAM in cervical cancer: A narrative review

Martina Romanova, Jaroslav Klat — 2026-01-06 12:13:37

Cervical cancer remains a major contributor to cancer-related mortality among women worldwide, despite substantial progress in prevention and treatment strategies. While established prognostic factors such as tumor size, lymphovascular space invasion, and nodal status guide clinical decision-making, they lack sufficient specificity for individualized risk stratification. Consequently, there remains an unmet need for robust biomarkers capable of reliably predicting recurrence and treatment response. L1 cell adhesion molecule (L1CAM), a neural adhesion protein implicated in epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis, has emerged as a candidate prognostic marker in several solid tumors, including gynecologic malignancies. Its role in cervical cancer, however, remains insufficiently defined. This narrative review synthesizes preclinical evidence and clinical studies evaluating L1CAM expression in cervical cancer, with an emphasis on its biological rationale, methodological challenges, and prognostic significance across different disease contexts. Data from early-stage and from locally advanced disease were critically appraised. Most early-stage studies have not demonstrated an independent prognostic effect of L1CAM, although associations with adverse histopathological features have been reported. In contrast, recent multicenter evidence suggests that high-level L1CAM expression (≥50%) may predict inferior pelvic control in patients undergoing chemoradiotherapy, underscoring a potential context-dependent prognostic role. Current evidence emphasizes the need for standardized immunohistochemistry protocols, prespecified positivity thresholds, and integration of L1CAM assessment with other. Prospective, adequately powered studies are essential to validate L1CAM as a clinically actionable biomarker and to determine whether its incorporation into prognostic models can enhance treatment personalization in cervical cancer.

Effects of intravesical cocktail instillation on outcomes and serum pain factors of patients with bladder pain syndrome

Yunpeng Jia, Yuanning Zhang, Bo Wang, Junjia Shi — 2025-11-11 15:09:11

Aims. We aimed to assess the effects of intravesical cocktail instillation on the outcomes and serum pain factors of patients with bladder pain syndrome (BPS). Methods. The clinical data of 86 female BPS patients hospitalized between March 2017 and March 2024 were collected for retrospective analysis. All patients were treated with oral medication (amitriptyline) + local intravesical instillation of drugs, and then assigned to a control group (sodium hyaluronate intravesical instillation) and a research group [intravesical instillation of dimethyl sulfoxide (DMSO) + chondroitin sulfate (CS) + low-molecular-weight heparin (LMWH) cocktail]. Results. The research group (n=43) had lower urination frequency in 24 h, Pelvic Pain and Urgency/Frequency Patient Symptom Scale score, and O'Leary-Sant interstitial cystitis symptom index and interstitial cystitis problem index, as well as larger single urination volume than those of the control group (n=43) after 3 and 6 months of treatment (P<0.05). In the serum, the levels of substance P (SP), 5-hydroxytryptamine (5-HT), prostaglandin E₂ (PGE₂), neuropeptide Y (NPY), β-endorphin (β-EP), and dopamine (DA) declined in the two groups after 1 month of treatment in comparison to the pre-treatment levels. The levels of SP, 5-HT, PGE₂, and NPY were lower, while the levels of β-EP and DA were higher in the research group than those in the control group (P<0.05). Conclusion. The intravesical instillation of DMSO + CS + LMWH cocktail is superior in long-term outcomes. It is more conducive to improving the levels of serum pain factors, with a good safety profile and without increasing adverse reactions.

Efficacy and safety of bifidobacterium triple viable capsules combined with entecavir in the treatment of Hepatitis B cirrhosis

Rongquan Liu, Yun Ji, Jie Zhang — 2025-10-02 08:14:21

Background. Liver cirrhosis caused by hepatitis B is a critical progression of chronic hepatitis B. It is often accompanied by intestinal dysbiosis and impaired intestinal mucosal barrier function, which further exacerbate hepatic inflammation and fibrosis. Therefore, exploring effective combined therapeutic approaches to improve patient outcomes is of significant importance. Objective. This study compares the efficacy and safety of entecavir combined with bifidobacterium triple viable capsules versus entecavir alone in treating Hepatitis B cirrhosis. Methods. This retrospective case-control study enrolled 110 patients with Hepatitis B cirrhosis diagnosed and treated from January 2021 to January 2024. The control group received entecavir alone, while the observation group received entecavir combined with bifidobacterium triple viable capsules Efficacy was assessed at 24 weeks and 48 weeks post-treatment. Comparisons were made between the two groups regarding changes in intestinal flora count, intestinal mucosal barrier function, liver function, HBV-DNA negativity rate, liver fibrosis indices, liver stiffness measurement (LSM), inflammatory factor indices, and treatment safety. Results. At 24 weeks and 48 weeks post-treatment, the observation group exhibited significant modulation of the intestinal microecology, with a notable decrease in the count of pathogenic bacteria (Candida albicans, Enterobacteriaceae, Enterococcus) in feces compared to pre-treatment and the control group (all P<0.05), and a significant increase in the count of probiotics (Lactobacillus, Bifidobacterium) (all P<0.05). Meanwhile, the observation group showed more significant improvement in intestinal mucosal barrier function, with lower levels of endotoxin, D-lactic acid, and diamine oxidase compared to the control group (all P<0.05). Regarding liver-related indices, the observation group demonstrated significantly greater improvement in liver function (ALT, AST, TBIL, ALB), liver fibrosis markers (HA, PC-III, IV-C, LN), and LSM compared to the control group (all P<0.05), with more pronounced improvement at 48 weeks than at 24 weeks (P<0.05). Notably, the observation group exhibited a higher HBV-DNA negativity rate at 48 weeks (90.91% vs 76.36%, P=0.039) and superior regulation of inflammatory factors (decreased TNF-α, IL-6, IL-8, and increased IL-10) (all P<0.05). The final clinical efficacy assessment revealed a significantly higher total effective rate in the observation group compared to the control group (83.64% vs 65.45%, P=0.029). Adverse event rates were comparable between the observation and control groups (7.27% vs. 10.91%, P=0.507), supporting the safety of the intervention. Conclusion. The treatment regimen of bifidobacterium triple viable capsules combined with entecavir is significantly superior to entecavir alone in improving intestinal flora, repairing the intestinal mucosal barrier, promoting liver function recovery, and alleviating liver fibrosis in patients with Hepatitis B cirrhosis. It also demonstrates more pronounced long-term efficacy, a higher HBV-DNA negativity rate, superior overall clinical efficacy, and good safety.

Validity of the AMS questionnaire for screening hypogonadism in men with type 2 diabetes: A cross-sectional study

2025-10-01 10:56:46

Background. Hypogonadism is common among men with type 2 diabetes mellitus (T2DM), but diagnosis can be confounded by overlapping symptoms from diabetic complications. The Aging Males' Symptoms (AMS) questionnaire is widely used for screening, yet its validity in this specific population remains unclear. Objective. To evaluate the relationship between AMS scores and serum testosterone levels in men with T2DM, assess diagnostic accuracy at various AMS cut-offs, and examine the influence of diabetic comorbidities on AMS scores. Methods. We conducted a cross-sectional study in 158 men with T2DM. Participants completed the AMS questionnaire and underwent morning testosterone measurement. Comorbidities such as neuropathy, nephropathy, and obstructive sleep apnea were assessed. AMS diagnostic performance was evaluated using different cut-off values (≥27, 30, 35, 40). Results. AMS total score showed a modest inverse correlation with testosterone (ρ = -0.16, P=0.047), primarily driven by the physical subscale. Neuropathy and nephropathy were associated with higher sexual subscale scores. An AMS ≥27 cut-off had high sensitivity (91%) but poor specificity (21%) for testosterone <12 nmol/L. Conclusion. AMS scores correlate weakly with testosterone levels in men with T2DM. Diabetic complications can elevate AMS scores independently, suggesting the need for caution and possibly higher cut-offs when using AMS for hypogonadism screening in this population.

Minimal residual disease and prognostic significance of circulating tumour cells in early-stage colorectal cancer

2025-08-20 09:42:09

Aim. The recurrence rate of colorectal cancer remains high even after radical surgery. Existing criteria for administering adjuvant treatment lack sufficient precision, often leading to undertreatment or overtreatment. This study investigates circulating tumour cells (CTCs) as a potential prognostic biomarker to improve the accuracy of patient selection. Methods. Forty-six colorectal cancer patients without distant metastases who underwent radical surgery were enrolled in this prospective study conducted at Tomas Bata Hospital in Zlín. The study protocol was approved by the hospital's Ethics Committee. Circulating tumour cells (CTCs) were measured in peripheral blood samples collected preoperatively, on the second postoperative day, and one month after surgery. CTCs were detected and characterized using semiautomated microscopy. Comprehensive clinicopathological data were recorded as part of standardized perioperative care. The prognostic significance of CTCs was evaluated based on the time to recurrence (TTR) parameter. Results and Conclusion. Growing evidence from circulating tumour cell (CTC) research supports their potential role as a valuable biomarker in cancer management. In this study involving stage I-III colorectal cancer patients, a recurrence rate of 20% was observed among individuals with detectable CTCs, whereas no recurrence occurred in patients with a sustained absence of CTCs. Despite this apparent difference, the time to recurrence (TTR) did not differ significantly between the groups (log-rank test, P=0.175). Although the result was not statistically significant, the observed trend suggests a possible prognostic value of CTCs that merits investigation in a larger cohort. Furthermore, neither individual time-point measurements nor dynamic changes in CTC levels demonstrated a significant correlation with TTR.