Advances in Clinical and Experimental Medicine最新文献

Background: Hepatocellular carcinoma (HCC) shows significant differences in incidence and mortality between genders.

Objectives: This study investigates the mechanisms by which estrogen receptors (ER), specifically ERα, influence HCC outcomes.

Material and methods: Bioinformatics approaches were used to study estrogen and its related pathways in relation to HCC. Estrogen receptor expression levels, along with downstream circular RNAs (circRNAs) and microRNAs (miRNAs), were measured in MHCC97H cells via quantitative reverse transcription polymerase chain reaction (RT-qPCR). Western blot was used to assess estrogen receptor 1 (ESR1) and SMAD family member 7 (SMAD7) protein expression. Cell proliferation, migration and cell cycle status of MHCC97H cells were measured using Cell Counting Kit-8 (CCK-8), Transwell assays and flow cytometry for cell cycle analysis.

Results: Bioinformatics analysis revealed that ERα acts as a transcription factor (TF) for 9 circRNAs with differential expression in HCC. We constructed the ERα/circRNA/miRNA/SMADs network based on the downstream targets of circRNAs, which were associated with the SMADs family. Survival studies revealed that ESR1 is correlated with favorable patient survival in liver cancer. In MHCC97H cells, qRT-PCR findings showed low expression of ESR1, hsa_circ_0004913 and SMAD7, but significant expression of hsa-miR-96-5p. Overexpression of ESR1 significantly increased the expression of hsa_circ_0004913 and SMAD7 while suppressing hsa-miR-96-5p. Western blot analysis confirmed these findings. Furthermore, ESR1 overexpression reduced MHCC97H cell proliferation and migration while inhibiting growth through G1 phase arrest. ESR1 acts as a TF that binds to the promoter of hsa_circ_0004913, as demonstrated using chromatin Immunoprecipitation followed by chromatin immunoprecipitation-quantitative real-time PCR (ChIP-qPCR). A dual-luciferase reporter experiment confirmed that hsa_circ_0004913 targets and regulates hsa-miR-96-5p.

Conclusions: ERα can function as aTF, modulating the expression of various circRNAs with differential expression in HCC. Through this regulation, it modulates the circRNA/miRNA/SMADs network, thereby inhibiting the progression of HCC.

Background: Breast cancer remains a major healthcare challenge, highlighting the need for early and accurate diagnosis. Shear-wave elastography (SWE), an ultrasound-based imaging technique that quantifies tissue elasticity, has emerged as a promising tool. Recent studies suggest that SWE may provide additional diagnostic value when used alongside conventional imaging methods.

Objectives: This study aimed to assess the diagnostic performance of SWE when combined with conventional ultrasound and magnetic resonance imaging (MRI) in the evaluation of breast lesions.

Material and methods: This retrospective study included patients with breast lesions who underwent SWE, conventional ultrasound and MRI. The diagnostic performance of each modality was evaluated individually and in combination. Histopathological results served as the gold standard for diagnosis. Key performance metrics - sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy - were calculated for each imaging approach.

Results: A total of 99 patients were included in the study, comprising 64 with benign lesions and 35 with malignant lesions. Malignant lesions were generally larger and exhibited distinct imaging characteristics across ultrasound, SWE and MRI. When assessed individually, SWE, ultrasound and MRI showed comparable diagnostic accuracy (64.6%, 62.6% and 62.6%, respectively). However, combining all 3 modalities significantly improved diagnostic performance, yielding sensitivity, specificity, PPV, NPV, and overall accuracy of 94.3%, 89.1%, 82.5%, 96.6%, and 90.9%, respectively (p < 0.001). The area under the curve (AUC) for the combined approach was significantly higher than for any single modality (0.917 vs 0.642, 0.627 and 0.633; p < 0.001).

Conclusions: While SWE alone offers diagnostic performance comparable to that of ultrasound and MRI individually, its greatest value lies in combination with these imaging modalities. Integrating ultrasound, SWE and MRI significantly enhances diagnostic accuracy, sensitivity and specificity, offering a promising multimodal approach for more reliable differentiation between benign and malignant breast lesions.

The rising prevalence of chronic diseases presents a major challenge to healthcare systems worldwide, particularly within primary care. While advances in diagnostics and therapeutics have improved disease management, traditional care models often neglect the individual contexts and lived experiences of patients. Personalized medicine (PM) offers a paradigm shift from standardized treatment approaches toward patient-specific care, integrating biological, behavioral and psychosocial dimensions to optimize outcomes. This editorial synthesizes findings from the Regions4PerMed (Horizon 2020) project, encompassing focus groups, stakeholder surveys and best practice analyses across 20 European countries. Stakeholders from government, academia, patient organizations and healthcare practice, identified key barriers to PM implementation, including fragmented data systems, insufficient clinician training and limited patient engagement. Cross-border data exchange standards, integration of real-world evidence (RWE) and sustainable funding mechanisms emerged as critical enablers of progress. The transition from concept to practice requires aligning policy, technology and human factors. Personalized care extends beyond genomics and precision therapies to encompass communication, motivation and shared decision-making. Training healthcare professionals in holistic competencies, enhancing digital literacy and promoting trust in data-driven systems are essential for successful adoption. By reframing personalization as both a scientific and relational endeavor, PM can strengthen chronic disease care through more adaptive, patient-centered models. Coordinated action across policy, education and technology domains is vital to embed personalization into everyday clinical practice and ensure sustainable, equitable healthcare delivery across Europe.

Background: Major depressive disorder (MDD) is frequently comorbid with mild cognitive impairment (MCI), yet its molecular basis remains unclear.

Objectives: This study aimed to identify shared differentially expressed genes (DEGs) and biological pathways that may underlie the comorbidity between MDD and MCI. Using integrative bioinformatics approaches applied to transcriptomic datasets, we sought to uncover molecular biomarkers that could inform early diagnosis and provide novel targets for mechanism-based therapeutic strategies.

Material and methods: Transcriptomic datasets from MDD (GSE58430) and MCI (GSE140831) patients were analyzed to identify DEGs. Functional enrichment analyses were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were constructed to identify core genes.

Results: A total of 301 DEGs were shared between MDD and MCI. Gene Ontology and KEGG enrichment analyses revealed key biological processes involved in neuroinflammation, oxidative stress, synaptic dysfunction, and apoptotic signaling. The PPI network analysis identified nine hub genes with high connectivity: HSP90AB1, CDC42, NFKB1, CD8A, CALM3, PARP1, CD44, H2BC21, and MYH9.

Conclusions: These findings reveal shared molecular biomarkers and pathways linking MDD and MCI, providing insights into their comorbidity. The identified core genes, particularly PARP1 and CDC42, may serve as novel targets for early diagnosis and mechanism-based therapeutic strategies in psychiatry and neurodegenerative disorders.

Background: Noninvasive ventilation (NIV) is an important treatment modality in the management of chronic obstructive pulmonary disease (COPD) by reducing respiratory distress, improving gas exchange and reducing exacerbations without the need for intubation and invasive airways.

Objectives: To synthesize data from randomized controlled trials (RCTs) and perform a meta-analysis to understand the beneficial effects of NIV across different COPD stages.

Material and methods: A systematic literature review was performed using MEDLINE (PubMed) and Cochrane Register of Controlled Trials (CENTRAL) al databases for RCTs that involved the administration of NIV vs usual treatment (oxygen supplementation, pharmacological agents, nasal cannulation) in patients with stable COPD, acute exacerbations of COPD (AECOPD), and post-exacerbation COPD (PECOPD). Mortality, exacerbation and intubation rates, and arterial blood gases (PaCO2 and PaO2 levels) were assessed in both groups. RevMan software was used to assess the risk of bias and calculate the pooled odds ratio (OR), mean differences (MDs) and subgroup analyses with a random-effects model.

Results: A total of 51 RCTs were included in the meta-analysis with information from 3,775 patients. Meta-analysis of the data showed that there was a significant decrease in mortality outcomes (p < 0.001), intubation frequency (p < 0.001) and PaCO2 levels (p < 0.001) but no significant improvement in exacerbation frequency (p = 0.12) and PaO2 levels (p = 0.69). Subgroup analyses demonstrated no significant difference between COPD stage on mortality outcomes (p = 0.32), PaCO2 level (p = 0.12) and PaO2 level (p = 0.64). There was a significant decrease in intubation rate in AECOPD patients receiving NIV and a statistically nonsignificant difference in exacerbation frequency in stable COPD patients using NIV.

Conclusion: The findings of this meta-analysis indicate a substantial overall enhancement in the frequency of exacerbations and intubations, mortality outcomes, and arterial gas levels among patients in various stages of COPD. Consequently, it is imperative to identify patients with COPD that are most likely to benefit from the use of NIV.

This review summarizes the latest advancements in stem cell (SC) mitochondrial proteomics. With the rapid development of biotechnology, mitochondrial proteomics has emerged as a pivotal area in SC research. The research methods used in mitochondrial proteomics include mass spectrometry (MS), with pre-MS sample processing, MS data acquisition employing both qualitative and quantitative approaches, and bioinformatics analysis to annotate and explore protein functions. In recent years, mitochondrial proteomics research has contributed to the establishment and expansion of our understanding of the roles of various mitochondrial proteins involved in regulating SC differentiation, metabolism and aging, including Drp1, Mfn1/2, OPA1, SIRT3, Bcl-2, YME1L, and PGC-1α. This multidisciplinary approach, combining qualitative and quantitative proteomics with bioinformatics, sheds light on the intricate regulatory mechanisms of mitochondrial proteins in SC. These findings provide a scientific basis for developing novel therapeutic targets and strategies, thereby advancing the field of regenerative medicine and personalized treatment paradigms.

Bacterial pneumonia is a cause of HIV-associated morbidity and mortality. Recurrent pneumonia, defined as 2 or more episodes within a 12-month period, is an AIDS-defining illness. The prevalence of bacterial pulmonary infections in HIV-infected patients has been decreasing with the introduction and widespread use of antiretroviral therapy. In well-developed settings, the frequency of bacterial pneumonia in people living with HIV is comparable to that in the general population. Studies have shown that the cumulative incidence of pneumonia is higher in HIV-infected patients with advanced immunosuppression, airflow limitation, smoking, intravenous drug use, or in those from underdeveloped countries and urban areas. In HIV-infected patients with community-acquired bacterial pneumonia, Streptococcus pneumoniae and Haemophilus species are the most frequently isolated pathogens. However, in untreated or poorly adherent HIV-infected individuals, opportunistic infections may occur. Although the incidence of opportunistic infections among HIV-infected patients has declined in well-developed settings due to the widespread use of antiretroviral therapy, tuberculosis remains a serious threat and a major cause of morbidity and mortality among HIV-infected individuals worldwide. Early diagnosis of HIV infection, timely initiation of antiretroviral therapy with good adherence, and promotion of vaccination remain priorities. This editorial provides an overview of community-acquired pneumonia in HIV-infected patients and discusses recent changes in its epidemiology and etiology.

Background: Research documenting the results of liver trauma surgery revealed a connection between prophylactic drainage (PD) and escalating infections or septic consequences.

Objectives: Meta-analysis research was conducted to review the wound complications (WCs) frequency of PD in liver resections (LRs).

Material and methods: Up until June 2024, comprehensive literature study was completed, and 757 related studies were reviewed. The 10 selected studies included 5,459 LRs at the beginning; 2,918 of them were drained and 2,541 were not. The dichotomous approaches and a fixed or random model were used to assess the WCs frequency of PD in LRs using odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: Prophylactic drainage had significantly higher surgical site wound infection rate (OR = 1.97; 95% CI: 1.09-3.55, p = 0.02) compared to non-PD in in LR patients, though no significant difference was found among PD and non-PD in LR patients in infected intra-abdominal collections (IIACs; OR = 3.17; 95% CI: 0.93-10.80, p = 0.07).

Conclusion: Prophylactic drainage had a considerably greater surgical site wound infection rate, and there was no discernible difference between IIACs and non-PD in LR individuals. Nevertheless, because there were not many studies nominated for comparison in the meta-analysis, care must be used when working with its outcomes, and further research is warranted to confirm these findings.

Background: Breast cancer (BC) is now the most common malignancy in women. Early detection and precise diagnosis are essential for improving survival.

Objectives: To develop an integrated computer-aided diagnosis (CAD) system that automatically detects, segments and classifies lesions in mammographic images, thereby aiding BC diagnosis.

Material and methods: We adopted YOLOv5 as the object-detection backbone and used the Curated Breast Imaging Subset of the Digital Database for Screening Mammography (CBIS-DDSM). Data augmentation (random rotations, crops and flips) increased the dataset to 5,801 images, which were randomly split into training, validation and test sets (7 : 2 : 1). Lesion-classification performance was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC), precision, recall, and mean average precision at a 0.5 confidence threshold (mAP@0.5).

Results: The CAD system yielded an mAP@0.5 of 0.417 and an F1-score of 0.46 for lesion detection, achieved an AUC of 0.90 for distinguishing benign from malignant lesions, and processed images at 65 fps.

Conclusions: The integrated CAD system combines rapid detection and classification with high accuracy, underscoring its strong clinical value.

Background: Amiodarone is the most commonly used class III antiarrhytmic drug with antiarrhytmic and vasodilator properties. Adenosine triphosphate (ATP) serves as a crucial source of intracellular energy, while resveratrol is known for its potent antioxidant activity.

Objectives: This study aimed to biochemically, histopathologically and immunohistochemically evaluate the effects of ATP, resveratrol and their combination on potential liver damage and dysfunction induced by amiodarone in rats.

Material and methods: The rats were divided into 6 groups: healthy control (HG), amiodarone alone (ADG), amiodarone + ATP at 2 mg/kg (AAG-2), amiodarone + ATP at 5 mg/kg (AAG-5), resveratrol + amiodarone (RAG), and resveratrol + amiodarone + ATP at 2 mg/kg (RAA-2). Amiodarone (50 mg/kg, orally), ATP (2 mg/kg and 5 mg/kg, intraperitoneally) and resveratrol (25 mg/kg, orally) were administered once daily for 14 days. Following treatment, liver tissues were excised for biochemical analysis. Oxidative stress was assessed by measuring malondialdehyde (MDA) levels, while antioxidant status was evaluated through total glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. To assess liver function, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in serum samples collected from the animals' tail veins. In addition, liver tissues were subjected to histopathological and immunohistochemical examination to evaluate structural and molecular changes associated with treatment.

Results: Amiodarone administration led to a significant increase in oxidative stress markers and a reduction in antioxidant levels in rat liver tissue. Additionally, serum levels of ALT and AST were elevated, indicating liver dysfunction. Histopathological and immunohistochemical analyses revealed severe (grade 3) oxidative damage in the liver tissue. All biochemical parameters in the 5 mg/kg ATP and resveratrol + 2 mg/kg ATP treatment groups were comparable to those observed in the HG group. Histopathological and immunohistochemical evaluations showed a reduction in liver damage severity to grade 2 in the groups treated with ATP (2 mg/kg) and resveratrol alone, and to grade 1 in the groups receiving ATP (5 mg/kg) or the combination of resveratrol + ATP (2 mg/kg).

Conclusions: The results of the present study suggest that adjusting the ATP dosage or using a combination of ATP and resveratrol may be effective strategies for minimizing amiodarone-induced liver damage.