Balkan Medical Journal最新文献

{"title":"HPV16 E7-Containing Exosomes May Contribute to PD-L1 Expression in Tumor-Infiltrating Lymphocytes of Cervical Cancer.","authors":"Yajing Zhang, Guqun Shen, Li Luo, Yangchun Feng, Senyu Wang","doi":"10.4274/balkanmedj.galenos.2026.2026-6-20","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2026.2026-6-20","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus 16 (HPV16) plays a major role in the development of cervical cancer (CC). Programmed cell death ligand 1 (PD-L1) expression in tumor-infiltrating lymphocytes (TILs) is an important feature of the tumor immune microenvironment and may affect responses to immune checkpoint blockade. However, the relationship between the HPV16 E7 oncoprotein and PD-L1 expression in TILs remains unclear.</p><p><strong>Aim: </strong>To investigate the presence of HPV16 E7 protein in exosomes from CC tissues and plasma, determine the association between exosomal E7 and PD-L1 expression in TILs, and explore whether E7-rich tumor-derived exosomes contribute to increased PD-L1 expression in TILs.</p><p><strong>Study design: </strong>This study combined clinical observational analyses and <i>in vitro</i> experiments. Three CC single-cell RNA sequencing datasets, a 30-patient HPV16-positive cohort, and a 104-patient tissue microarray cohort were analyzed. <i>In vitro</i> experiments were conducted to further examine the potential relationship between exosomal E7 and PD-L1 expression in TILs.</p><p><strong>Methods: </strong>Blood and pathological samples from 30 patients with HPV16-positive CC, as well as culture fluid from the C33A and SiHa CC cell lines, were collected. Exosomes were isolated, and E7 protein expression was assessed. Bioinformatics analyses of CC single-cell RNA sequencing datasets were performed to evaluate CD274 mRNA expression in TILs. Immunohistochemistry (IHC) was used to assess PD-L1 protein expression in TILs in the 30-patient cohort, while multiplex immunofluorescence was used to evaluate E7 and PD-L1 expression in TILs in a 104-patient tissue microarray. Exosome uptake by TILs was assessed using confocal microscopy. TILs were co-cultured with exosomes, and HPV16 E7 and PD-L1 expression was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting in the TIL blank control, co-culture blank control, co-culture empty vector, and co-culture E7-overexpression groups.</p><p><strong>Results: </strong>E7 protein was detected in exosomes from the peripheral blood of 28 of 30 patients (93.3%) and in exosomes from SiHa cell culture. PD-L1 was expressed in TILs, with a positive rate of 43.3% (13/30). In the tissue microarray cohort (n = 103; 28 events), higher CD3<sup>+</sup>PD-L1<sup>+</sup>/CD3<sup>+</sup> expression was associated with poorer survival (HR = 2.97, <i>p</i> = 0.009). CD3<sup>+</sup>E7<sup>+</sup>/CD3<sup>+</sup> expression showed a borderline association with poorer survival in the dichotomized analysis (HR = 2.15, <i>p</i> = 0.052) but was significantly associated with survival when modeled as a continuous variable (per 10%: HR = 1.28, <i>p</i> = 0.002). In the 30-patient cohort, exosomal E7 protein content was significantly associated with PD-L1 expression in TILs (Cramér's V = 0.728, <i>p</i> = 0.0001). qRT-PCR and western blotting demonstra","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anterior Quadratus Lumborum Block for Postoperative Analgesia in Hip Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis.","authors":"Burhan Dost, Yunus Emre Karapinar, Esra Turunc, Engin İhsan Turan, Madan Narayanan, Dario Bugada, Alessandro De Cassai","doi":"10.4274/balkanmedj.galenos.2026.2026-8-37","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2026.2026-8-37","url":null,"abstract":"<p><strong>Background: </strong>Postoperative pain following hip surgery remains challenging to manage despite the use of multimodal analgesia. Anterior quadratus lumborum block (aQLB) has been proposed as an effective regional analgesic technique; however, its clinical efficacy remains uncertain.</p><p><strong>Aims: </strong>To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate whether aQLB reduces postoperative opioid consumption and pain following hip surgery.</p><p><strong>Study design: </strong>Systematic review and meta-analysis.</p><p><strong>Methods: </strong>PubMed, Scopus, Embase, CENTRAL, and Web of Science were systematically searched through March 2026. The primary outcome was 24-hour postoperative opioid consumption. Random-effects models were used for all pooled analyses. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and the certainty of evidence was evaluated using the GRADE approach. Subgroup and sensitivity analyses and trial sequential analysis were also performed.</p><p><strong>Results: </strong>Sixteen RCTs involving 994 patients were included in the analysis. aQLB reduced 24-hour postoperative opioid consumption, expressed as morphine milligram equivalents (MME) (mean difference, -6.60 mg; 95% confidence interval, -10.46 to -2.74; <i>p</i> = 0.003; I² = 94%). aQLB also reduced pain scores, postoperative nausea and vomiting (PONV), and rescue analgesic requirements, with no significant differences in time to rescue analgesia, mobilization, or hospital stay. The certainty of evidence was low for 24-hour MME, pain at rest across all assessed time points, and rescue analgesic requirements, and moderate for pain during movement at 6 hours and PONV.</p><p><strong>Conclusion: </strong>aQLB was associated with statistically significant reductions in 24-hour postoperative opioid consumption, early postoperative pain at rest, rescue analgesic requirements, and PONV after hip surgery. However, the magnitude of these benefits was small and did not consistently exceed established thresholds for clinical importance, and the certainty of evidence remained low.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Who Owns Cardiovascular-Kidney-Metabolic Care?","authors":"Mehmet Çelik, Servet Altay","doi":"10.4274/balkanmedj.galenos.2026.2026.290926","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2026.2026.290926","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel <i>TBC1D15::RAB21</i> Variant in T-Cell Acute Lymphoblastic Leukemia.","authors":"Zhan Su, Ren Zhong, Chunting Zhao","doi":"10.4274/balkanmedj.galenos.2026.2026-8-23","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2026.2026-8-23","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Paraganglioma Presenting with Spinal Cord Edema.","authors":"Yang Yang, Lanlan Feng, Yanli He","doi":"10.4274/balkanmedj.galenos.2026.2026-7-57","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2026.2026-7-57","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Endoscopy is Insufficient: Endovascular Management of Duodenal Varices in a Pediatric Patient.","authors":"Wioletta Guzik, Natalia Stalony, Krzysztof Korzeniowski, Kinga Kowalska-Duplaga, Aleksandra Banaszkiewicz","doi":"10.4274/balkanmedj.galenos.2026.2026-7-60","DOIUrl":"10.4274/balkanmedj.galenos.2026.2026-7-60","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNF113A Promotes Colorectal Cancer Metastasis by Regulating TGF-β Pathway and EMT via Ubiquitin-Mediated Degradation of SNIP1.","authors":"Kaoyan Feng, Mengbin Qin, Peng Peng, Wenfang Yang, Xiaoping Pan, Yanlin Tan, Sijie Yang, Jiean Huang, Jinxiu Zhang","doi":"10.4274/balkanmedj.galenos.2026.2026-7-40","DOIUrl":"10.4274/balkanmedj.galenos.2026.2026-7-40","url":null,"abstract":"<p><strong>Background: </strong>RNF113A is a RING finger protein that is upregulated in colorectal cancer (CRC). Smad nuclear-interacting protein 1 (SNIP1) negatively regulates the transforming growth factor-beta (TGF-β) pathway in CRC and plays a significant role in disease progression; however, its precise regulatory mechanism remains unclear.</p><p><strong>Aims: </strong>To investigate whether RNF113A is associated with SNIP1 protein stability and TGF-β pathway modulation in CRC and to explore the potential underlying molecular mechanisms.</p><p><strong>Study design: </strong><i>In vitro</i> experimental study.</p><p><strong>Methods: </strong>Immunohistochemistry and correlation analyses were performed on clinical CRC specimens to assess the expression relationships among RNF113A, SNIP1, and TGF-β1. CRC cell clonogenic capacity and migration were evaluated using colony formation, wound healing, and transwell assays. Co-immunoprecipitation was used to assess protein-protein interactions. Protein stability was examined via RNF113A overexpression and knockdown, with or without proteasome inhibition (MG132). TGF-β pathway-related protein expression and epithelial-mesenchymal transition markers were assessed by qPCR and Western blotting, using TGF-β1 (pathway activator) and SB525334 (ALK5 inhibitor) for pharmacological modulation.</p><p><strong>Results: </strong>RNF113A expression was inversely correlated with SNIP1 and positively correlated with TGF-β1 in clinical specimens. Functionally, RNF113A promoted CRC cell clonogenic capacity and migration. Mechanistically, RNF113A interacted with SNIP1. RNF113A overexpression decreased SNIP1 protein levels, whereas RNF113A knockdown increased them. This effect was reversed by MG132, suggesting ubiquitin-proteasome-mediated degradation.</p><p><strong>Conclusion: </strong>This study suggests that RNF113A is associated with SNIP1 ubiquitination and degradation, potentially modulating TGF-β signaling and CRC cell migration. These findings reveal a potential RNF113A/SNIP1/TGF-β regulatory axis and highlight RNF113A as a potential therapeutic target in CRC, warranting further mechanistic validation.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"575-585"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Habitat Imaging-Based Radiomics and Deep Learning Fusion for Preoperative Prediction of Lymphovascular Invasion in Invasive Breast Cancer: A Multicenter Study.","authors":"Lichang Zhong, Kui Wang, Juan Xie, Lin Shi, Liping Gu, Yuanyi Zheng, Xiaolei Yi","doi":"10.4274/balkanmedj.galenos.2026.2026-7-3","DOIUrl":"10.4274/balkanmedj.galenos.2026.2026-7-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Lymphovascular invasion (LVI) is a critical prognostic factor in invasive breast cancer; however, reliable preoperative prediction remains challenging because of the lack of non-invasive and accurate assessment tools. Ultrasound-based radiomics and deep learning have shown promise, but conventional single-modality approaches often fail to capture intratumoral heterogeneity, thereby limiting their predictive performance and clinical interpretability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;To develop and validate a non-invasive ultrasound-based model that integrates habitat radiomic features with deep learning features for the preoperative prediction of LVI in invasive breast cancer and to evaluate whether this model could enhance the diagnostic performance of radiologists.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design: &lt;/strong&gt;Retrospective multicenter diagnostic study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 1,096 patients from three institutions were included. Tumors on routine B-mode ultrasound were partitioned into three habitats using unsupervised k-means clustering (k = 3). Habitat2, identified as a high-risk subregion associated with LVI, was used for selective radiomic feature extraction. In parallel, deep learning features from all habitat subregions were extracted using a pretrained ResNet50 model. Radiomic and deep learning features were fused at the feature level, and a LightGBM classifier was trained and evaluated in an internal validation cohort and two independent external cohorts. Model performance was compared with that of the Habitat2 radiomics-only and ResNet50-only models using the DeLong test and with the performance of unaided senior and junior radiologists. Biological interpretability was assessed through correlation analysis with CD31-stained microvessel density.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The fusion model achieved areas under the receiver operating characteristic curve (AUCs) of 0.918 (training), 0.898 (internal validation), 0.890 (External Cohort 1), and 0.905 (External Cohort 2), significantly outperforming the Habitat2 radiomics-only and ResNet50-only models (DeLong test: fusion vs. Habitat2 radiomics, all &lt;i&gt;p&lt;/i&gt; &lt; 0.001; fusion vs. ResNet50, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, 0.021, 0.029, and 0.026, respectively). Habitat-specific radiomic and deep learning features showed weak-to-moderate correlations with CD31-stained microvessel density, supporting the biological interpretability of the model. Compared with radiologists, the fusion model achieved higher diagnostic performance than unaided senior and junior radiologists in both external cohorts, and model assistance substantially improved the performance of junior radiologists (AUCs up to 0.865 and 0.905).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This interpretable habitat-deep learning fusion approach based on routine ultrasound provides accurate preoperative LVI prediction with robust generalizability across multiple centers and suggests the potential to enhance clinical d","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"563-574"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misdiagnosis and Reflections on Two Cases of Placental Site Trophoblastic Tumors.","authors":"Hong-Ju He, Li-Juan Hao","doi":"10.4274/balkanmedj.galenos.2026.2026-7-6","DOIUrl":"10.4274/balkanmedj.galenos.2026.2026-7-6","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"591-593"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testosterone Therapy After TRAVERSE: Rethinking Cardiovascular and Prostate Cancer Safety.","authors":"Gökhan Çevik, Ateş Kadıoğlu","doi":"10.4274/balkanmedj.galenos.2026.2026.310826","DOIUrl":"10.4274/balkanmedj.galenos.2026.2026.310826","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"543-545"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}