Advances in Clinical and Experimental Medicine最新文献

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.

Background: Amputation followed by index finger pollicization is the gold-standard treatment for type III B thumb hypoplasia. However, despite its high success rate, some parents decline this procedure because it results in a four-finger hand.

Objectives: To evaluate the outcomes of reconstructive surgery in eight patients with type III B thumb hypoplasia, stabilized using a non-vascularized proximal interphalangeal (PIP) joint harvested from the foot when parental consent for pollicization was not granted.

Material and methods: The study cohort comprised 8 postoperative patients (mean follow-up: 7 years) who underwent reconstructive stabilization of a hypoplastic thumb using a PIP joint from the foot. Hand function was evaluated by measuring range of motion (ROM), thumb stability and length, grip strength, and performance on a manual manipulation test. Donor-site morbidity was assessed via foot examination following PIP joint harvest. Functional outcomes were further analyzed using specialized patient-reported questionnaires.

Results: Most patients achieved good thumb stability and a functional passive range of motion. Reconstructed thumbs averaged approx. 75% of the length of a normal thumb, and grip strength measured about 50% of that in the contralateral hand. Donor-site assessment revealed toe shortening in the majority of cases but no deficits in ambulation or weight-bearing. The overall complication rate was 25%, and most patients and their parents reported satisfaction with the treatment.

Conclusions: Thumb reconstruction with a non-vascularized PIP joint yields enhanced stability and reduced hypermobility, with outcomes comparable to those reported for similar techniques. This approach represents a viable alternative for patients whose parents decline pollicization.

Background: Basket trials are an innovative type of clinical trial primarily used in oncology. A distinctive feature of these studies is the grouping of patients based on specific molecular characteristics, such as genetic mutations or immunological subtypes, rather than traditional criteria like the type of cancer.

Material and methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medical databases were searched for studies published between 2014 and 2024. The inclusion criteria focused on basket trials as a clinical trial model in oncology.

Objectives: This work aims to outline the principles of conducting basket trials in oncology, analyze basket trials from the past decade, and highlight the emerging trends in this type of trial.

Results: The analysis of 76 articles meeting the inclusion criteria revealed that most of these studies are conducted as phase II clinical trials. The average duration of the basket trials in the analysis was 5.9 years (mean = 5.05), with an average recruitment target of 326 patients (mean = 123.5). Most of these studies were conducted in the USA, and the majority of basket trials focused on patients with solid tumors.

Conclusion: The systematic review confirms that basket trials have significant potential as a clinical trial model, as evidenced by the increasing number of basket trial projects being conducted.

Background: Research on the psychological distress experienced by women with benign breast disease (BBD) remains limited, though some evidence suggests it may resemble that of women with breast cancer (BC).

Objectives: This study aimed to use the Distress Thermometer (DT) to assess the levels of psychological distress and identify influencing factors during the diagnostic phase in patients with BC and BBD.

Material and methods: From October 2022 to May 2023, a questionnaire survey incorporating the DT and Problem List (PL) was conducted among inpatients in the diagnostic phase for BC or BBD at the Breast Surgery Department of Shanxi Bethune Hospital (Taiyuan, China). Statistical analysis, including descriptive and inferential methods, was performed to examine factors affecting psychological distress in patients with BBD and BC.

Results: In this study, 373 participants were evaluated for psychological distress during the diagnostic phase. Among 255 patients diagnosed with BBD, the median distress score was 4, with a distress prevalence of 52%. The primary sources of distress included anxiety (43.5%), fear (21.2%), pain (7.1%), sleep disturbances (6.7%), and childcare responsibilities (5.1%). Among 118 BC patients, the median distress score was slightly higher at 4.5, with a distress prevalence of 63.6%. Key distress factors were anxiety (47.5%), fear (33.1%), financial worries (21.2%), depression (18.6%), and sadness (15.3%). Key predictors of distress varied between the 2 groups. For patients diagnosed with BBD, younger age, lower education levels, unemployment, and a higher Breast Imaging Reporting and Data System (BI-RADS®) classification significantly contributed to higher distress levels. In patients diagnosed with BC, younger age, lower education levels, and unemployment were the primary risk factors.

Conclusions: These findings underscore the psychological burden faced by both patient groups during diagnosis, highlighting the need for early identification and management of distress in this population.

Background: Multidrug resistance remains a major obstacle in the treatment of ovarian cancer (OC) patients. Recent research has underscored the critical role of extrachromosomal circular DNA (eccDNA) in tumor initiation and progression. However, there is limited comprehensive understanding of the role eccDNA plays in tumor resistance.

Objectives: This study investigates the involvement of WWP1-eccDNA in the resistance mechanisms of OC.

Material and methods: Human OC cells (SKOV3 and cisplatin-resistant SKOV3/DDP) were cultured and high-throughput sequencing was performed, leading to the identification of eccDNA in SKOV3/DDP cells. Female BALB/cA-nu nude mice with SKOV3 and SKOV3/DDP xenografts received cisplatin (5.5 mg/kg), hydroxyurea (50 mg/kg) or saline for 14 days, followed by tumor weight assessment. Digital droplet polymerase chain reaction (ddPCR) and real-time quantitative polymerase chain reaction (qPCR) were used to quantify WWP1-eccDNA, evaluating their sensitivity and accuracy. Linear DNA removal and BsmI digestion were tested to improve eccDNA detection.

Results: WWP1-eccDNA was among the top upregulated eccDNA in SKOV3/DDP cells. Both cisplatin and hydroxyurea reduced tumor growth in mice, with cisplatin showing limited efficacy in resistant tumors. The ddPCR outperformed RT-qPCR in sensitivity, and linear DNA removal improved WWP1-eccDNA detection. WWP1-eccDNA levels were significantly elevated in SKOV3/DDP tumors. Treatment with cisplatin further increased its expression, whereas hydroxyurea led to a reduction in WWP1-eccDNA levels.

Conclusions: WWP1-eccDNA is critical in OC resistance, with cisplatin treatment increasing WWP1-eccDNA levels, contributing to resistance. The ddPCR proves to be a superior method for eccDNA detection.