Advances in Clinical and Experimental Medicine最新文献

Background: Osteoarthritis (OA) and chondrosarcoma (CHS) are joint-disabling diseases that differ in their clinical manifestations, pathobiological mechanisms and management strategies.

Objectives: This study aims to investigate the cellular heterogeneity and molecular mechanisms underlying osteoarthritis and CHS using single-cell RNA sequencing and molecular docking approaches, with the goal of identifying potential therapeutic targets.

Material and methods: Publicly available single-cell RNA sequencing datasets for osteoarthritis and CHS were retrieved for detailed analysis. The t-distributed stochastic neighbor embedding method (t-SNE) and the uniform manifold approximation and projection (UMAP) method were used to visualize cellular clustering, and differential expression analyses were performed to evaluate key genes across distinct cell populations. Additionally, we conducted a computational study, including molecular docking of the DAP3 protein with the natural compounds curcumin and resveratrol, to assess their potential as therapeutic agents.

Results: We identified significant differences in the distribution of cell subpopulations and gene expression profiles between OA and CHS. Only selected cell subgroups - including neurons, chondrocytes and immune cells - exhibited tissue-specific expression differences in disease-associated genes. In silico molecular docking demonstrated that curcumin and resveratrol can bind to the DAP3 protein suggesting a potential molecular basis for developing novel therapeutic strategies.

Conclusions: This study provides detailed single-cell insights into OA and CHS and identifies potential therapeutic targets. These findings not only deepen our understanding of the cellular and molecular features of these diseases but also highlight promising avenues for future therapeutic development.

Background: Since older patients are at high risk of hypotension and hypoxia during anesthesia, it is crucial to choose safe sedatives.

Objectives: To compare the efficacy and safety of remimazolam with propofol in elderly patients undergoing endoscopic procedures.

Material and methods: This multicenter, single-blind, randomized study included patients aged ≥65 years (American Society of Anesthesiologists (ASA) physical status I-III) who were randomized in a 1:1 ratio to receive either remimazolam (0.1-0.2 mg/kg) or propofol (0.3-0.5 mg/kg). The primary endpoint was the rate of occurrence of hypotensive events. Secondary endpoints included time to patient unresponsiveness and time to awakening (defined as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤3 and ≥4), time to leaving the operating room, cognitive function assessment (using the Mini-Cog test), and additional parameters.

Results: A total of 300 patients aged ≥65 years were enrolled. Patients who received remimazolam (n = 132) experienced a significantly lower incidence of intraoperative hypotension compared with those treated with propofol (n = 138) (56.8% vs 82.6%, p < 0.001). The median time to reach a MOAA/S score of 3 was shorter in the remimazolam group than in the propofol group (1.17 min [interquartile range (IQR): 0.85-1.44] vs 1.33 min [IQR: 0.88-2.00], p = 0.041). At 10 min post-awakening, the median Ramsay sedation score was lower in the remimazolam group (2.03 ±0.17 vs 2.14 ±0.35, p = 0.001). Tukey's post hoc analysis showed a significant decline in cognitive scores before and after anesthesia in the propofol group (p = 0.002), whereas no significant change was observed in the remimazolam group (p = 0.658). There was no significant difference in treatment-related adverse events (AEs) between the 2 groups.

Conclusions: Remimazolam significantly reduced the incidence of intraoperative hypotension during colonoscopy, providing a safer sedative option for elderly patients and supporting its use as a preferred agent in this population.

Alzheimer's disease (AD) remains one of the most pressing challenges in contemporary neurology, with growing evidence highlighting the limitations of the amyloid hypothesis and monomodal therapies. This editorial advocates for a shift toward multidimensional research and therapeutic frameworks that integrate molecular, electrophysiological, neuroimaging, and behavioral data. Emphasis is placed on the potential of microRNA-based biomarkers, electroencephalography (EEG) analysis, and non-invasive methods to improve early diagnosis. Emerging multimodal treatment strategies - including immunotherapy, neurostimulation, and nutraceuticals - are discussed alongside ethical and regulatory challenges in implementing novel interventions. The authors propose an integrated, patient-centered model that combines precision medicine with preventive approaches rooted in lifestyle, digital biomarkers, and AI-powered personalization. A paradigm shift toward systemic, translational, and ethically grounded strategies is urgently needed to meet the growing burden of AD.

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.

Congenital heart disease (CHD) remains the foremost cause of mortality in children under 20 years of age. Given their ease of harvest, robust proliferative capacity and multilineage differentiation potential, stem cells (SCs) have emerged as a promising therapeutic alternative. In particular, mesenchymal stem cells (MSCs) derived from Wharton's jelly in the umbilical cord, i.e., an abundant byproduct of childbirth, especially in lowand middle-income settings, can be induced toward a cardiomyocyte lineage, making them an attractive cell source for cardiac regeneration. Although MSCs can be directed toward a cardiomyocyte lineage using growth factors or chemical cues, most in vitro-differentiated cells remain developmentally immature, with only a small fraction achieving the structural, functional and metabolic maturity required for therapeutic use. In resource-limited laboratories, the primary challenge is to develop a simple, cost-effective protocol that reliably differentiates MSCs into structurally, functionally and metabolically mature cardiomyocytes. This review presents a streamlined, cost-effective in vitro differentiation protocol for umbilical-cord MSCs into cardiomyocytes, designed for laboratories with minimal resources, involving 3 sequential stages. First, induce cardiac mesoderm commitment by treating umbilical cord-derived MSCs (UC-MSCs) with 5-azacytidine (5-Aza) or bone morphogenetic protein (BMP). Next, specify cardiac progenitor cells by adding a Wnt-pathway inhibitor (e.g., IWP-2). Finally, drive cardiomyocyte maturation by supplementing the culture with insulin-like growth factors (IGFs). In laboratories lacking complex bioreactors, seeding the cells onto a simple biocompatible scaffold, such as a collagen or fibrin hydrogel, can further boost differentiation efficiency and promote tissue-like organization.

Background: Pancreatic cancer (PC) is among the most aggressive and lethal malignancies, characterized by development within a complex tumor microenvironment (TME) that includes a desmoplastic stroma composed of extracellular matrix (ECM) and various cellular components.

Objectives: This study aims to elucidate the cellular and molecular mechanisms regulating PC progression through an integrated analysis of single-cell pseudotime trajectories and intercellular communication.

Material and methods: We constructed pseudotime trajectories using single-cell RNA sequencing (scRNA-seq) data from PC tissues to trace the developmental progression of cancer cells. Transitional cell states and critical genes involved in the shift from early-to-advanced disease stages were identified. Through a comprehensive analysis, we pinpointed key transcription factors and signaling pathways implicated in tumor progression. Expression of stemness-associated genes in pancreatic stellate cells (PSC) was validated using immunofluorescence and transmission electron microscopy (TEM). Additionally, cell-cell communication analysis was performed to examine interactions within the TME, with particular emphasis on ligand-receptor pairings.

Results: Our analysis identified key transcription factors and signaling pathways that drive the cellular transitions associated with cancer progression. The findings revealed extensive intercellular crosstalk between cancer cells, stromal fibroblasts, and diverse immune cell subpopulations. Notably, the study underscored the distinct functional contributions of these cell populations to tumor development, immune evasion and metastatic dissemination.

Conclusions: The study uncovers the complex cellular diversity and intercellular crosstalk in PC, providing novel avenues for therapeutic interventions and early predictive markers in diagnosis. These findings support the potential for more targeted, personalized treatment strategies in combating PC.

Background: Abdominal aortic aneurysm (AAA) is a cardiovascular condition characterized by the abnormal dilation of the abdominal aorta.

Objectives: A circular RNA (circRNA) microarray was utilized to identify differentially expressed circRNAs in angiotensin II (Ang II)-stimulated AAA mice.

Material and methods: Male apolipoprotein E-deficient (apoE-/-) mice were randomly assigned to 2 groups and subjected to 28 days of infusion with either Ang II or saline. At the end of the experiment, the mice were euthanized via exsanguination under anesthesia. The periadventitial tissues were carefully removed from the aortic wall to measure the maximal external diameter of the suprarenal aorta, and then stored for further analysis. Samples from both the control and AAA groups were used for circRNA expression profiling. The R package Bioconductor was employed to perform Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Arraystar's proprietary miRNA target prediction software, integrating miRanda and TargetScan, was used to predict the circRNA/miRNA interactions. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to confirm the reliability of the microarray results.

Results: A total of 13,103 circRNAs were detected. Compared to the control group, 90 circRNAs were upregulated and 234 were downregulated in the Ang II-induced AAA group. Gene Ontology analysis indicated that the target genes associated with the differentially expressed circRNAs were involved in a variety of biological processes. The KEGG pathway analysis revealed that the differentially expressed circRNAs influenced several critical pathways, including the MAPK signaling pathway, insulin signaling pathway, Ras signaling pathway, and autophagy. The results of RT-qPCR showed that the expression levels of circRNA_30395, circRNA_30398 and circRNA_012594 were significantly increased in AAA, while circRNA_006097 and circRNA_009932 were notably decreased. The top 5 miRNAs related to each validated circRNA were identified through bioinformatic analysis. Among these differentially expressed circRNAs, miR-136-5p was predicted to be the target gene of circRNA_30398 with high probability.

Conclusions: The differential expression of various circRNAs identified in AAA suggests that the circRNA-miRNA-mRNA axis may serve as a potential molecular regulatory mechanism for AAA.

Background: Phonemic awareness is defined as the ability to break down a word into smaller units called phonemes or described as the ability to synthesize words from segments of one's own speech. Impaired phonemic hearing, depending on the degree of severity, hinders or prevents speech reception, disrupts the proper development of a child's pronunciation, may cause disorders in already developed speech, and complicates the acquisition of writing skills or disturbs the skill that has already been acquired.

Objectives: To create an objectified tool for phonemic hearing diagnostics to ensure that verbal material is always presented at the same intensity, from the same distance, and in the same direction. Another aim was to compare children with and without auditory processing disorder (APD) if they have disrupted phonemic hearing.

Material and methods: A study involving 20 individuals was conducted using a sound level meter to determine the level of the auditory stimulus (therapist's voice) provided to patients during the diagnosis. Each participant in the study was tasked with repeating, in the most natural way for them, 2 pairs of words containing opposing sounds.

Results: The analysis revealed significant discrepancies both in the articulation of verbal material by different examiners and in the presentation of the same material by a single examiner using different methods. When the same phonemic opposition was presented in an identical manner by different diagnosticians, amplitude differences of up to 10.8 dB were observed, with a standard deviation (SD) of 2.5 dB. These findings underscored the need to develop an objectified tool for phonemic hearing diagnostics to ensure consistency and reliability in assessment.

Conclusions: In the research group encompassing children with APD, disorders within phonemic hearing occur more frequently and have a deeper nature. Phonemic hearing disorders in children are associated with significant difficulties in learning and daily functioning.

The 2025 Nobel Prize in Physiology or Medicine honored the seminal discovery that regulatory T cells (Tregs) restrain immune responses and prevent autoimmunity through peripheral immune tolerance. However, to obtain a holistic view of peripheral immune tolerance, it is also necessary to consider the role of mesenchymal stem/stromal cells (MSCs) in this process. Therefore, I propose a two-tier model that incorporates both Tregs and MSCs, with Tregs acting within the immune system as an "internal checkpoint" to temper effector cell activity, and tissue-resident MSCs - or "master signaling cells" - serving as an "external checkpoint." Injuryor pathogen-induced inflammation activates MSCs, which in turn secrete a broad repertoire of immunomodulatory molecules, create a local anti-inflammatory milieu, promote tissue repair, and directly dampen excessive immune activity at the site of damage. The concerted actions of Tregs and MSCs are essential for effective peripheral immune tolerance, shielding the host from pathogens and collateral tissue injury. This model helps explain the pathophysiology of autoimmunity and tumor immune evasion, as well as the therapeutic potential of MSC-based interventions.

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.