Advances in Clinical and Experimental Medicine最新文献

Background: Emergency medical teams are a crucial component of healthcare systems, routinely providing essential care to pregnant patients in various situations.

Objectives: To evaluate the rate and outcomes of out-of-hospital deliveries attended by Emergency Medical Services (EMS) in Poland and identify areas for improvement in the care provided by emergency medical teams.

Material and methods: This retrospective study was based on 41,335 EMS emergency calls to women in advanced pregnancy, of which 879 births were delivered directly by medical teams between January 2018 and December 2022. Data were obtained from the Polish National Monitoring Center for Emergency Medical Services, encompassing all EMS interventions in Poland.

Results: The study involved 879 EMS team interventions for pregnant women, with an average patient age of 29.87 years. Most patients were in their 2nd pregnancy (28.26%) and delivering for the 2nd time (25.77%). The postnatal condition of newborns, assessed using the Apgar score, was missing in 408 cases (46.52%) due to incorrect completion of documentation. Emergency Medical Services teams, predominantly P-type (basic) teams, handled 69.78% of deliveries, while S-type (specialist) teams were involved in 30.22% of cases. Medical procedures often performed during childbirth included manual assistance in spontaneous delivery, pulse oximetry, physical examination, examination of systemic blood pressure, obtaining peripheral intravenous access, and gynecological examination.

Conclusions: Given the rate of encountered cases and the gaps identified in medical documentation, there is merit in potentially implementing a dedicated form to be completed by medical teams when caring for a pregnant patient. Ongoing training and enhancements in the range of assistance provided to the mother and newborn are imperative for ensuring appropriate care.

Transcranial direct current stimulation (tDCS) has emerged as a widely accessible, noninvasive technique capable of modulating cortical excitability. A rapidly expanding body of sports-science literature suggests that it can produce modest but measurable gains in endurance, strength, skill acquisition, and perceived exertion. This editorial reviews the physiological mechanisms underlying tDCS, evaluates the evidence for its ergogenic effects, and situates the technology within the broader framework of "neurodoping". Applying the 2021 World Anti-Doping Agency (WADA) Code, I argue that tDCS already satisfies 2 of the 3 criteria for prohibition - namely, potential performance enhancement and violation of the spirit of sport - while failing the 3rd criterion, as standard protocols pose minimal health risk. This editorial also considers practical and ethical counterarguments to a ban, including tDCS's low cost, relative safety, requirement for continued training effort, and the near-impossibility of detection or enforcement. Drawing parallels with accepted performance aids such as mindfulness, nutrition and altitude tents, this editorial concludes that outright prohibition could drive use underground and impede open scientific scrutiny. Instead, it advocates rigorous long-term safety monitoring, transparent research, and nuanced policy development that distinguishes therapeutic from performance applications. Ultimately, it frames tDCS as a "still-legal" yet ethically contested innovation at the frontier of sports technology, urging stakeholders to balance principles of fair play with scientific evidence as the debate over neurodoping continues to evolve.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune inflammatory disease with a multisystem manifestation and a variety of clinical symptoms. Over the last decades, the prognosis and life expectancy of patients with SLE improved significantly due to the implementation of corticosteroids combined with immunosuppressive agents. Nevertheless, the use of these medications is often associated with the occurrence of serious side effects and additional deterioration of organ function. Therefore, developing and implementing novel therapies that are both safer and more effective in managing disease is crucial. For a long time, European Alliance of Associations for Rheumatology (EULAR) recommended only 2 biological agents in the treatment of SLE: belimumab and rituximab. However, in 2023, anifrolumab, an interferon (IFN) receptor inhibitor, and voclosporin, a novel calcineurin inhibitor, appeared in new SLE treatment guidelines. In addition, several biological agents are targeting different cells or cytokines that are being evaluated in phase II and III clinical trials. Apart from that, experimental therapies such as targeting of plasma cells, chimeric antigen receptor T-cell therapy (CAR-T) or stem cell transplantation appear promising in the treatment of the severe forms of SLE.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Due to the lack of symptoms until advanced stages, early diagnosis of ccRCC is challenging. Therefore, the identification of novel secreted biomarkers for the early detection of ccRCC is urgently needed.

Objectives: This study aimed to identify novel secreted biomarkers for diagnosing ccRCC using bioinformatics and machine learning techniques based on transcriptomics data.

Material and methods: Differentially expressed genes (DEGs) in ccRCC compared to normal kidney tissues were identified using 3 transcriptomics datasets (GSE53757, GSE40435 and GSE11151) from the Gene Expression Omnibus (GEO). Potential secreted biomarkers were examined within these common DEGs using a list of human secretome proteins from The Human Protein Atlas. The recursive feature elimination (RFE) technique was used to determine the optimal number of features for building classification machine learning models. The expression levels and clinical associations of candidate biomarkers identified with RFE were validated using transcriptomics data from The Cancer Genome Atlas (TCGA). Classification models were then developed based on the expression levels of these candidate biomarkers. The performance of the models was evaluated based on accuracy, evaluation metrics, confusion matrices, and ROC-AUC (receiver operating characteristic-area under the ROC curve) curves.

Results: We identified 44 DEGs that encode potential secreted proteins from 274 common DEGs found across all datasets. Among these, insulin-like growth factor binding protein 3 (IGFBP3) and lectin, galactoside-binding, soluble, 1 (LGALS1) were selected for further analysis using the RFE technique. Both IGFBP3 and LGALS1 showed significant upregulation in ccRCC tissues compared to normal tissues in the GEO and TCGA datasets. The results of the survival analysis indicated that patients with higher expression levels of these genes exhibited shorter overall and disease-free survival times (OS and DFS). Decision tree and random forest models based on IGFBP3 and LGALS1 levels achieved an accuracy of 98.04% and an AUC of 0.98.

Conclusions: This study identified IGFBP3 and LGALS1 as promising novel secreted biomarkers for ccRCC diagnosis.

Background: Patients with aortic arch lesions involving the left subclavian artery (LSA) usually require endovascular surgery. The Castor single-branch stent graft provides a targeted solution for such cases, with potential benefits enhanced by the direction-turnover and unwrapping techniques.

Objectives: To evaluate the safety, efficacy and short-term outcomes of the direction-turnover joint unwrapping techniques combined with a Castor single-branch stent graft in treating aortic arch lesions involving the LSA.

Material and methods: From January 2022 to June 2023, 18 patients with aortic arch and LSA lesions underwent Castor stent graft placement at Binzhou Medical University Hospital (Shangdong, China). Preoperative and postoperative imaging with computed tomography angiography (CTA) was used to assess stent placement and efficacy at 1, 3, 6, and 12 months post-surgery.

Results: All 18 patients successfully received the stent graft without intraoperative complications, stent migration or residual shunting. Postoperative imaging confirmed accurate stent placement with no evidence of thrombosis or endoleaks.

Conclusions: The direction-turnover and unwrapping techniques improve the accuracy and safety of Castor stent graft placement, effectively reducing guidewire entanglement and enhancing procedural success. These techniques show promise for broader application in complex aortic arch interventions.

Background: Out-of-hospital cardiac arrests (OHCA) are a major global health concern, occurring frequently worldwide. Obesity may impact outcomes in OHCA patients.

Objectives: This study aimed to assess the impact of obesity on the return of spontaneous circulation (ROSC) in OHCA patients, considering sex differences.

Material and methods: A retrospective cohort study was conducted, analyzing medical records of patients assisted by the Emergency Medical System (EMS) in Poland from January 2021 to June 2022. The study included 33,636 patients with OHCA. Obesity status was determined using ICD-10 codes (E66) and descriptive diagnoses recorded by EMS teams.

Results: Univariate analysis indicated that obesity decreased the odds of ROSC by 25.47% (odds ratio (OR) = 0.75, 95% confidence interval (95% CI): 0.61-0.92) in women and by 19.76% (OR = 0.80, 95% CI: 0.66-0.97) in men. However, multivariate analysis, adjusting for confounding variables, did not confirm a statistically significant impact of obesity on ROSC outcomes. The likelihood of ROSC was significantly higher in individuals with an initial ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) rhythm compared to Asystole/pulseless electrical activity (PEA), being 4.204 times higher in women (95% CI: 3.525-5.014) and 3.655 times in men (95% CI: 3.320-4.023). Out-of-hospital cardiac arrest in a public place increased the odds of ROSC more than twofold for both sexes (women: OR = 2.20, 95% CI: 2.00-2.43; men: OR = 2.13, 95% CI: 1.98-2.29). Among women without obesity, hypertension decreased the odds of ROSC by 11.11% (OR = 0.89, 95% CI: 0.81-0.99).

Conclusions: Our study demonstrated that obesity was not an independent predictor of ROSC in OHCA patients. Different predictors of ROSC were identified for men and women. Initial VF/pVT rhythm, location of OHCA and age were the significant factors influencing ROSC.

Background: Intracranial aneurysm (IA) is a serious condition that can lead to a life-threatening rupture, often resulting in a hemorrhagic stroke. Vascular smooth muscle cell (VSMC) dysfunction is a critical factor in the pathogenesis of IA, yet the molecular mechanisms underlying this relationship are not yet fully understood. Recent studies suggest that circular RNAs (circRNAs) are involved in various vascular diseases. High-throughput sequencing identified hsa_circ_0008433 as significantly upregulated in IA tissues, especially in ruptured cases, suggesting a role in IA progression.

Objectives: To further investigate the potential effects of hsa_circ_0008433 on the rupture of human IA.

Material and methods: This study aimed to investigate the effects of hsa_circ_0008433 on IA rupture. We validated the expression of hsa_circ_0008433 in IA patient tissue samples through reverse transcription quantitative polymerase chain reaction (RT-qPCR), comparing ruptured and unruptured aneurysms. Human brain vascular smooth muscle cells (HBVSMCs) were utilized to establish overexpression and knockdown models for hsa_circ_0008433. Cell Counting Kit-8 (CCK-8) and wound healing assays were conducted to assess cell proliferation and migration, while western blotting was employed to measure VSMC phenotype markers including α-smooth muscle actin (α-SMA), smooth muscle protein 22-alpha (SM22α), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9).

Results: The RT-qPCR analysis confirmed that hsa_circ_0008433 was significantly upregulated in IA tissues, especially in ruptured samples (p < 0.05). Overexpression of hsa_circ_0008433 in HBVSMCs promoted proliferation, migration and phenotype switching, indicated by increased expression of MMPs and decreased contractile proteins. The effects were reversed by the knockdown of hsa_circ_0008433.

Conclusions: We have shown that hsa_circ_0008433 regulates vascular smooth muscle cell function and promotes behaviors that may lead to intracranial aneurysm instability. This study advances the understanding of the role of circRNAs in vascular pathology and identifies hsa_circ_0008433 as a potential therapeutic target for IA. These findings open opportunities for targeted treatments and broader applications in vascular disease research.

Sleep disorders have emerged as a significant public health issue, adversely affecting quality of life and precipitating severe complications. The association between obstructive sleep apnea syndrome (OSAS) and otolaryngological manifestations appears to be underrecognized. This study posits that manifestations in the ear, nose and throat (ENT) among patients with OSAS and users of continuous positive airway pressure (CPAP) therapy are relatively common. Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, this systematic review, registered at PROSPERO (No. CRD42023452473), involved a comprehensive search of the MEDLINE databases. We included studies published in English from 1979 to March 2021 that explored the linkages between OSAS, CPAP and otolaryngological manifestations. A total of 29 articles were reviewed, with findings indicating 12 studies on ear dysfunctions, 11 on nose dysfunctions and 6 on pharynx dysfunctions. Reported symptoms included hearing dysfunction, vestibular function disorders, cerebrospinal fluid leak, Eustachian tube (ET) dysfunction, rhinosinusitis, olfaction and taste disorders, dysphagia, dry mouth, and gastroesophageal reflux. The etiology of these ailments varies, yet an understanding of these symptoms can improve the diagnosis to confirm or rule out OSAS. Early identification of ENT symptoms related to OSAS may facilitate prompt diagnosis and mitigate serious complications.

Background: Long-term peritoneal dialysis (PD) leads to peritoneal injury, with mesothelial-to-mesenchymal transition (MMT) potentially serving as an initial and reversible stage of this process. Indoxyl sulfate (IS), a protein-bound uremic toxin that accumulates in patients with declining renal function, is known to be associated with epithelial-mesenchymal transition (EMT) in proximal renal tubular cells. However, its effects on peritoneal mesothelial cells, which serve as the first-line barrier during PD, have not yet been investigated.

Objectives: This study aimed to evaluate whether IS induces MMT in human peritoneal mesothelial cells during PD through the β-catenin signaling pathway.

Material and methods: A human peritoneal mesothelial cell line (HMrSV5) was used for this in vitro study. Cells were treated with IS or combined with β-catenin inhibitor ICG-001, and high glucose PD fluid (PDF) served as a positive control. Morphology, proliferation and adhesion were assessed, while the expression of β-catenin and α-smooth muscle actin (α-SMA) as mesenchymal markers, along with E-cadherin as a mesothelial marker, were analyzed at both RNA and protein levels using real-time polymerase chain reaction (PCR) and western blot, respectively.

Results: The number of viable and adherent cells was significantly increased in the IS and PDF groups compared to the control (p < 0.05). Treatment with ICG-001 significantly reduced both viable and adherent cell numbers compared to cells treated with IS or PDF alone (p < 0.05). At the RNA level, IS treatment significantly decreased E-cadherin expression (p = 0.002) while significantly increasing β-catenin (p = 0.001) and α-SMA (p = 0.002) expression compared to the control group. These changes were reversed by ICG-001 treatment. Protein expression showed similar trends.

Conclusions: Indoxyl sulfate induces MMT in human peritoneal mesothelial cells, and these changes can be reversed by the specific β-catenin inhibitor ICG-001. This suggests that IS may be considered as another inducer of MMT during PD through the β-catenin signaling pathway.

Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which is characterized by a lack of sensitive and specific biomarkers.

Objectives: This study investigates the association between ELAV-like RNA binding protein 1 (ELAVL1) and HCC patient outcomes.

Material and methods: This retrospective study encompassed 108 HCC patients who reported to Wuhan Fourth Hospital and Tongji Hospital, China, from January 2016 to August 2020. Clinical data collected included age, sex, body mass index (BMI), comorbidities, tumor-node-metastasis (TNM) stage, Barcelona Clinic Liver Cancer (BCLC) stage, and lymphatic metastasis. All patients received routine follow-up for survival and recurrence status ranged from 36 to 60 months. The serum levels of ELAVL1 were tested using enzyme-linked immuno-sorbent assay (ELISA). Levels of total bilirubin, alanine aminotransferase (ALT), aspartate transaminase (AST), HCC-related biomarkers of alpha fetoprotein (AFP), α-L-fucosidase (AFU), and carcinoembryonic antigen (CEA) were recorded.

Results: Our findings revealed a significantly higher expression of ELAVL1 in patients presenting with TNM stages III-IV, BCLC stages C-D, lymphatic metastasis, as well as deceased and recurrent patients. Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUCs) for ELAVL1 in predicting mortality, recurrence and poor prognosis (defined as mortality or recurrence) in HCC patients were 0.818, 0.732 and 0.827, respectively. Patients with higher expression of ELAVL1 showed significantly higher frequencies of TNM III-IV stages, BCLC D stage, lymphatic metastasis, higher mortality, and recurrence ratio, as well as higher AFP and CEA levels. ELAVL1 was positively correlated with levels of AFP and CEA. Higher BCLC stage, lymphatic metastasis, age, AFP, and ELAVL1 were independent risk factors for poor prognosis of HCC patients.

Conclusions: Higher serum levels of ELAVL1 are associated with worse clinical outcomes and poorer prognosis in ‑HCC patients.