Advances in Clinical and Experimental Medicine最新文献

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: 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.

Background: The neuroendocrine system's role in maintaining bodily homeostasis implicates it in insomnia, suggesting both causal relationships and therapeutic targets. Yet, studies examining the link between metabolic syndrome (MetS) components such as hypertension, elevated blood glucose levels and abnormal cholesterol and insomnia have been inconsistent. Some research suggests a correlation, proposing that metabolic dysfunctions might contribute to sleep disturbances. However, other studies found little to no significant connection, indicating the complexity of this relationship and the potential influence of genetic, lifestyle and environmental factors. These contradictory findings underscore the challenges in fully understanding the intricate interplay between metabolic health and sleep quality.

Objectives: To explore the relationship between MetS and insomnia.

Material and methods: This study used bidirectional two-sample Mendelian randomization (MR) analysis to determine the causal relationship between the characteristics of MetS components and insomnia. Based on Genome-Wide Association Studies (GWAS) public databases, we explored the causal relationship between waist circumference (WC), hypertension, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and the risk of insomnia. Sensitivity analysis was conducted to evaluate the stability, heterogeneity and potential presence of horizontal pleiotropy in the results.

Results: Waist circumference and hypertension were associated with an increased risk of insomnia (WC, odds ratio (OR) = 1.05, 95% confidence interval (95% CI): 1.03-1.06, p = 9.15e-07; hypertension, OR = 1.06, 95% CI: 1.02-1.10, p = 0.005). In the reverse MR analysis, there was no significant causal relationship between insomnia and WC, TG, HDL-C, and FBG.

Conclusions: Our study has demonstrated the close connection between MetS components and insomnia by genetic means, thereby guiding the future research direction of insomnia prevention and treatment.

Background: The impact of different systemic treatments on the health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC) is still unclear.

Objectives: To compare and evaluate the effects of various systemic interventions on the HRQoL in patients with mCRC.

Material and methods: A thorough search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to locate relevant literature published in peer-reviewed journals. The risk ratio (RR) and 95% confidence intervals (95% CIs) were calculated. The heterogeneity was examined using p-value, Cochrane Q and I² statistics. The analysis was performed with RevMan 5.4. At least 2 treatment regimens were tested in phase II or III trials. The primary objectives were shortand long-term mean changes in EORTC QLQ-C30 GHS/QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30, Global Health Status/Quality of Life) and EQ-5D health utility scores (EuroQol 5 Dimension). Multivariate meta-regression was used to combine direct and indirect comparison data into a network meta-analysis with a random-effects consistency model. The surface under the cumulative ranking (SUCRA) probability curve was used to compare different systemic therapy combinations.

Results: This meta-analysis involved 15 relevant randomized clinical trials (RCTs) with 7,699 patients with mCRC. The study had a low risk of bias (RoB) (p > 0.05 for Egger's regression test) and moderate heterogeneity (I2 < 60%). Results indicated that systemic therapies were substantially more effective than other agents in improving the overall survival (OS) of patients (RR: 0.85 (95% CI: 0.79-0.90); p < 0.001, I2 < 60%], ensuring progression-free survival (PFS) (RR 0.80 (95% CI: 0.75-0.85); p < 0.001; I2 < 60%), suggesting that there was moderate heterogeneity. Long-term findings demonstrated that cetuximab was the most effective treatment and was linked to a significant improvement in GHS/QoL.(coefficient [95% CI] = 0.23 [-0.68 to 0.96], p = 0.747). In terms of the longand short-term results of change in QLQ-C30 GHS/HUS QoL score, cetuximab performed the best (SUCRA 95.12%) among all therapies. It also showed a substantial advantage in comparison to chemotherapy (mean deviation (MD) 0.06, 95% CI: 0.01 to 0.09).

Conclusion: This network meta-analysis found that cetuximab monotherapy improves HRQoL and prolongs OS and PFS in patients with mCRC.

The introduction of artificial intelligence (AI) in healthcare has created novel challenges for the field of medical malpractice. As healthcare professionals increasingly rely on AI in their decision-making processes, traditional medicolegal assessments may struggle to adapt. It is essential to examine AI's role in clinical care - both its current applications and future advancements - to clarify accountability for diagnostic and therapeutic errors. Clinical decision support systems (CDSSs), in particular, unlike other traditional medical technologies, work as co-decision makers alongside physicians. They function through the elaboration of patient information, medical knowledge, learnt patterns, etc., to generate a decision output (e.g., the suggested diagnosis), which should then be evaluated by the physician. In light of the AI Act, CDSSs cannot function fully autonomously, but instead physicians are to be assigned an oversight role. It is questionable, however, whether it would always be appropriate to assign full responsibility, and consequently liability, to the physician. This would be especially true if oversight is limited to reviewing outputs generated by the CDSS in a manner that leaves no real control in the hands of the physician. Future research should aim to define clear liability allocation frameworks and design workflows that ensure effective oversight, thereby preventing unfair liability burdens.

Background: Mitochondrial dynamics is an important field in cell biology, encompassing mitochondrial fission and fusion. The balance between fission and fusion is responsible for the stability of the mitochondrial network and can be a regulator of mitochondrial function. Recent studies have emphasized that an imbalance in mitochondrial dynamics is the root cause of dysfunction and is involved in various stages, such as oxidative stress, inflammation and apoptosis. Reversing this imbalance can effectively alleviate disease conditions. Although the importance of mitochondrial dynamics has been widely recognized, there is still a lack of literature on the qualitative and quantitative description and analysis of advances in this field.

Objectives: This study is a bibliometric analysis of research trends, collaboration networks and thematic evolution in mitochondrial dynamics from 2000 to 2023.

Material and methods: Using the Web of Science Core Collection (WoSCC) database, we performed a bibliometric review, applying VOSviewer and CiteSpace to visualize and analyze publications, citations, collaborations, and key word trends.

Results: We analyzed 332 publications, identifying China and the USA as leaders in research output and international collaborations. Significant contributions were made by institutions like Chiang Mai University and the California Institute of Technology (Caltech), with major research shifts from basic mitochondrial functions to roles in diseases like Alzheimer's and cardiovascular disease.

Conclusion: Mitochondrial dynamics research has expanded, with increasing attention to its role in disease mechanisms. Future research should further explore these connections, potentially leading to innovative treatments.