Advances in Clinical and Experimental Medicine最新文献

Pulmonary arterial hypertension (PAH) is a rare and progressive syndrome that is frequently diagnosed at an advanced stage due to the nonspecific nature of its symptoms. Current research aims to identify novel diagnostic tools, including biomarkers, to facilitate earlier detection and differentiation of pulmonary hypertension (PH) subtypes. Matrix metalloproteinases (MMPs) play a critical role in the pathogenesis of PAH through extracellular matrix (ECM) remodeling, with their activity tightly regulated by tissue inhibitors of metalloproteinases (TIMPs). This review summarizes existing studies on the potential of MMPs and TIMPs as biomarkers for PAH. Our analysis highlights significant differences in MMP concentrations between PAH patients and healthy controls. In particular, MMP-2, MMP-7 and MMP-9 exhibit promising prognostic value, which could contribute to risk stratification and support clinical decision-making in the future. However, large-scale, randomized prospective studies involving well-characterized patient cohorts are necessary to confirm their clinical utility and clarify their mechanistic roles in PAH pathogenesis.

Breast cancer (BC) remains a leading cause of cancer-related mortality worldwide, underscoring the need for novel, more effective therapies. Neoantigen-based immunotherapy - which harnesses tumor-specific somatic mutations to boost immune recognition - has emerged as a particularly promising strategy. Advances in next-generation sequencing and computational immunopeptidomics now allow systematic mapping of the tumor mutanome and rapid identification of immunogenic neoantigens, enabling personalized vaccine design and more precise deployment of immune-checkpoint blockade. However, intratumor heterogeneity, immune-escape mechanisms and the often-limited intrinsic immunogenicity of individual neoepitopes continue to constrain clinical efficacy. This review synthesizes the current landscape of neoantigen-targeted immunotherapies in BC, outlines the principal obstacles to their broader impact and highlights emerging solutions - including improved epitope-prediction algorithms, multi-epitope vaccine constructs and synergistic combination regimens. A deeper understanding of the immunogenic mutanome is expected to translate into more durable and widely applicable treatments for patients with breast cancer.

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.

Clinical skills refresher courses focusing on competence are essential for enhancing the clinical performance of healthcare providers. These courses play a pivotal role in nursing and midwifery education, offering students initial exposure to clinical environments and preparing them for subsequent internships. This systematic review aimed to assess the effectiveness of clinical skills refresher courses on clinical performance, particularly focusing on competency-based supplementary clinical skills courses. A comprehensive literature search was conducted across articles published in the last 15 years, utilizing PubMed, Embase, Cochrane Library, Web of Science, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases with specific keywords. This extensive search yielded 1,751 records, of which 13 were selected based on strict inclusion and exclusion criteria. Of these, 5 studies examined the effect of competency-based education (CBE) on the quality of clinical skills, 5 studies assessed clinical skills in detail, and 3 studies discussed other variables related to nursing skills, such as anxiety. The results indicate that CBE significantly enhances clinical skills and self-efficacy among nursing students, addressing gaps in practical training and psychological readiness for clinical internships. This review recommends the implementation of well-organized competency-based training courses in nursing and midwifery education. By bridging the gap between theoretical knowledge and practical experience, this approach equips nurses and midwives to effectively address contemporary healthcare challenges, ultimately improving patient outcomes, enhancing professional confidence and ensuring adherence to healthcare standards.

Background: Septic shock in pediatric intensive care units (PICUs) requires accurate prognostic tools. The Sequential Organ Failure Assessment (SOFA) and the Phoenix Sepsis Score (PSS) are both widely used, yet their comparative effectiveness has not been fully established.

Objectives: To evaluate the prognostic sensitivity of the SOFA and PSS scores in predicting mortality among pediatric patients with septic shock, and to compare their performance across different patient subgroups.

Material and methods: This retrospective study included 110 pediatric patients with septic shock admitted to the PICU of Shanxi Children's Hospital between 2020 and 2024. SOFA and PSS scores were recorded at admission, along with demographic, clinical, and outcome data. Patients with congenital organ abnormalities or severe inherited metabolic disorders were excluded. Predictive accuracy was assessed using correlation analyses and receiver operating characteristic (ROC) curve analysis.

Results: Both SOFA and PSS scores showed moderate correlations with mortality (SOFA: r = 0.57; PSS: r = 0.56), with SOFA demonstrating slightly higher overall predictive accuracy. PSS exhibited greater sensitivity in severe cases. Neurological and respiratory dysfunctions were the strongest predictors of mortality, whereas coagulation parameters had minimal prognostic value. Age-specific analysis revealed that SOFA was more accurate in patients aged 1-3 years and >7 years, while PSS outperformed SOFA in children aged 3-6 years.

Conclusions: Both SOFA and PSS scores are effective tools for predicting mortality in pediatric septic shock. SOFA demonstrated superior overall performance, whereas PSS showed advantages in specific age ranges and disease categories. Using the two scoring systems in combination may support more informed clinical decision-making.

Background: The healing rate after treatment in patients with high anal fistula (HAF) remains low. In individuals with HAF, the loose combined cutting seton (LCCS) technique has shown promising effectiveness, demonstrating a high cure rate, low incidence of incontinence and reduced pain levels.

Objectives: To assess the long-term efficacy and safety of LCCS technique in patients with HAF.

Material and methods: The LCCS procedure was conducted in patients with HAF between December 2020 and February 2022. All participants were followed up for 12 months. The primary outcome was fistula healing, while secondary outcomes included fistula recurrence, visual analogue scale (VAS) pain score, severity of fecal incontinence, and quality of life.

Results: A total of 132 patients with HAF were included in the final analysis, with a mean follow-up duration of 17.0 ±3.8 months. At the 12-month follow-up, 130 patients (98.5%) achieved fistula healing. Among them, 103 patients who received primary HAF treatment at our center fully recovered, while 27 of 29 patients previously treated unsuccessfully at other hospitals achieved healing within 12 months, corresponding to a 93.1% success rate. Ninety patients (68.2%) reported no fecal incontinence at follow-up (Wexner Continence Grading Scale (WCGS) score = 0), and 42 patients had a WCGS score of 1. The LCCS procedure was associated with a persistently low risk of postoperative perianal discomfort, with 127 patients (96.2%) scoring 0 and only 5 (3.8%) scoring 1 on the VAS.

Conclusions: The LCCS technique is a safe and effective treatment for patients with HAF.

Background: Breast cancer (BC) is a heterogeneous disease classified into 4 molecular subtypes, each with distinct molecular characteristics that influence treatment strategies, clinical outcomes and prognosis. These subtypes are associated with specific changes in cellular metabolism, which may play a crucial role in tumor development and progression.

Objectives: To identify distinctive serum metabolic biomarkers for each molecular BC subtype and to evaluate their associations with estrogen receptor (ER) and human epidermal growth factor 2 (HER2) receptor status, thereby refining molecular classification and informing personalized treatment strategies.

Material and methods: The study utilized the proton nuclear magnetic resonance (1H NMR) metabolomics method to collect serum metabolic profiles from BC patients. Pattern recognition analysis was employed to analyze the metabolic data. Metabolic markers specific to each molecular subtype were selected, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was employed to explore serum metabolic pathway heterogeneity.

Results: Distinct metabolic markers were identified for each molecular subtype, demonstrating strong discriminatory power. Additionally, we identified specific serum metabolites whose levels correlate with ER and HER2 expression profiles. The KEGG pathway analysis revealed significant heterogeneity in serum metabolic pathways across different subtypes.

Conclusions: This study demonstrates pronounced metabolic differences across BC subtypes that mirror their distinct molecular profiles and may underlie variations in therapeutic response. These metabolomic insights hold promise for refining tumor classification, improving diagnostic accuracy and guiding more personalized treatment strategies.

Electroencephalography has advanced from spectral analyses to integrate functional-connectivity and oscillatory metrics, offering mechanistic insights into network dysfunction across neurological and psychiatric disorders. Methodological advances, such as source reconstruction and brain modelling, enhance spatial precision and mitigate volume conduction. Empirical studies show that oscillatory brain activity and functional connectivity serve human cognition and their disruptions underlie symptoms in a variety of neuropsychiatric disorders. The study of the relation between brain oscillations and connectivity is pivotal for the advances in cognitive and clinical neuroscience. Crucially, integrating these biomarkers into machine-learning frameworks and closed-loop neuromodulation holds promise for personalized diagnostics and interventions.

Background: Cognitive impairment (CI) is common in patients with alcohol-use disorder (AUD)-related liver cirrhosis, especially those awaiting liver transplantation (LT). There are conflicting results in terms of the role of hepatic encephalopathy (HE) in CI development and persistence.

Objectives: This study investigated the impact of hyperammonemia on CI and evaluated the role of routine magnetic resonance imaging (MRI) in detecting CI among patients with AUD-related cirrhosis listed for LT at a single center.

Material and methods: Fifty-two adults (36 males, 69%) with AUD-related liver cirrhosis (mean age: 51 ±11 years; mean Model for End-Stage Liver Disease (MELD) score 16 ±6) were evaluated. Cognitive function was assessed using the Addenbrooke's Cognitive Examination III (ACE-III), with scores below 82 indicating probable dementia. Magnetic resonance imaging evaluations focused on cortical-subcortical atrophy, vascular-origin changes, and chronic HE.

Results: Magnetic resonance imaging revealed HE-related changes in 38 patients (73%), vascular-origin changes in 32 patients (62%), and cortical-subcortical atrophy in 15 patients (29%). Cognitive impairment was present in 46 patients (88%), with 30 (58%) suspected of having dementia. Patients with MRI evidence of HE scored lower in the ACE III language subdomain (p = 0.032) and tended toward a higher Child-Pugh classification (p = 0.083). No significant differences were found in ACE-III results or clinical data between patients with and without vascular-origin changes or cortical-subcortical atrophy. Additionally, no correlations were observed between radiological findings, ammonia levels, ACE-III scores, and liver-related mortality.

Conclusions: These findings reveal a high prevalence of CI and significant MRI abnormalities in AUD patients awaiting LT. Further studies are needed to clarify the role of routine MRI in detecting cognitive deficits.

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.