2026-02-27 2026, Volume 10 Issue 1

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  • research-article
    Yuhang Yu, Yukai Tang, Shengyi Liu, Limin Liu

    Radiation myelopathy (RM) is a severe, late-onset complication of radiotherapy, involving complex pathological processes, such as vascular endothelial cell damage, disruption of the blood-spinal cord barrier, inflammation, demyelination, hypoxia, and tissue necrosis. Traditional treatments, including corticosteroids and immunoglobulins, can effectively alleviate acute symptoms, but their long-term use may cause side effects and offer limited efficacy, especially in advanced stages of the disease where significant neurological recovery remains challenging. In recent years, emerging therapeutic strategies for RM – such as neuromodulation technologies, stem cell transplantation, tissue engineering, and gene therapy – have gained increasing attention. These approaches promote spinal cord repair and functional recovery through mechanisms, such as neuroprotection, myelin regeneration, axonal regeneration, and immune modulation. In addition, the use of biomaterials, such as hydrogels and nanodelivery systems has enhanced the delivery efficiency and therapeutic efficacy of both drugs and cells. Future research should focus on optimizing intervention timing and developing combination treatment strategies – such as incorporating antifibrotic drugs, anti-inflammatory therapies, and hyperbaric oxygen therapy – to improve the microenvironment of injury and enhance therapeutic outcomes. This review evaluates the pathological mechanisms of RM, explores emerging therapeutic strategies, and highlights future research directions to improve clinical efficacy.

  • research-article
    Zhaoxia Qu, Xiaozhen Pen, Xingjun Lu, Shunli Luo

    Colorectal cancer is characterized by high prevalence, poor clinical outcomes, and unfavorable prognosis, significantly contributing to human mortality. It is well established that phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the pathogenesis and progression of colorectal cancer. In this review, we examine the role of the PI3K/AKT/mTOR signaling pathway in a variety of cellular processes, including proliferation, autophagy, apoptosis, angiogenesis, and epithelial-mesenchymal transformation in colorectal cancer. Furthermore, the latest advancements in the research on PI3K/AKT/mTOR inhibitors are discussed, offering new insights for targeted therapy in colorectal cancer.

  • research-article
    Fatima Zohra Attouahri, Boutaina Addoum, Leila Benbacer, Samira Mimount, Bouchra El Mchichi, Abdelhamid Barakat, Hanane El Ouazzani, Ismail Rhorfi, Ahmed Abid, Mouna Ababou, Khalid Ennibi, Khaoula Errafii, Mohammed El Mzibri

    Lung cancer (LC) remains the most common malignancy in both genders and is the leading cause of cancer-related death worldwide. Despite significant advances in therapeutic approaches, radiotherapy (RT) continues to be one of the main approaches to LC treatment. However, radioresistance represents a major challenge to effective disease management and contributes significantly to treatment failure and poor prognosis. Radioresistance can be intrinsic, existing before treatment, or acquired during RT. It is a highly complex and multifactorial mechanism involving various cellular and molecular processes that are not yet fully understood. Key mechanisms contributing to radioresistance include enhanced DNA damage repair, cell cycle redistribution, inhibition of apoptosis, disruption of intracellular signaling pathways, interaction with the tumor microenvironment, autophagy-mediated survival, cancer stem cell-related resistance, and deregulation of non-coding ribonucleic acids. Understanding these pathways is essential for identifying new therapeutic targets and developing strategies to overcome resistance and improve patient outcomes. This review provides a comprehensive overview of the molecular mechanisms underlying radioresistance in LC.

  • research-article
    Diogo Pinto da Costa Viana, Thiago Bracks Oliveira

    Obesity remains widely treated as a sex-neutral condition, despite decades of evidence revealing distinct sex-specific metabolic and behavioral trajectories between men and women. This neutrality perpetuates unequal outcomes: Men often achieve faster initial weight loss, whereas women face greater early resistance but display superior long-term resilience. The question persists: Why do men and women respond differently to the same intervention? The answer lies not in a single mechanism, but in the complex interplay among body composition, hormonal and neuroendocrine regulation, adaptive thermogenesis, and sociocultural determinants. To address this gap, this review proposes an integrative four-axis model encompassing: (i) Body composition and fat distribution, (ii) hormonal and neuroendocrine control, (iii) energy efficiency and adaptive thermogenesis, and (iv) sociocultural determinants. Drawing on literature from the past 25 years, it synthesizes physiological and behavioral evidence to explain how biological sex and menopausal status influence weight-loss responses. The narrative approach bridges clinical and experimental findings to offer a conceptual framework capable of guiding personalized strategies in obesity care. By integrating metabolic, hormonal, and psychosocial domains, the proposed model underscores that obesity cannot be reduced to a mere caloric equation. Recognizing sex-based dimorphism is essential for improving equity, sustainability, and precision in treatment outcomes. This framework invites a paradigm shift, from calorie-centered to complexity-informed medicine, where management is tailored to the distinct physiological and social realities of men and women.

  • research-article
    Inês Sousa, Diana Martins, Fernando Mendes

    Introduction: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, and its aggressive nature necessitates the development of alternative therapeutic strategies. Immune checkpoint inhibitors (ICIs) have shown remarkable success in LC treatment. Despite advances with programmed cell death protein-1/programmed cell death ligand-1 inhibitors, many patients experience limited or short-lived responses, prompting interest in novel ICIs such as T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain (TIGIT), lymphocyte-activation gene 3 (LAG-3), and indoleamine 2,3-dioxygenase 1 (IDO-1).

    Objectives: This narrative systematic review aimed to assess the clinical efficacy and safety of these novel ICIs compared to standard ICI therapy in LC.

    Methods: A systematic literature search was conducted across PubMed, Web of Science, and ClinicalTrials.gov. The search covered studies published from January 2020 to January 2025, to identify randomized controlled trials (RCTs) evaluating novel ICIs in LC. Due to substantial heterogeneity in study design, intervention targets, and outcome reporting, findings were synthesized narratively in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using RoB 2.

    Results: Five RCTs involving a total of 825 patients were included. TIGIT inhibition demonstrated benefit in progression-free survival and response rate. LAG-3 inhibitors showed mixed efficacy, with potential dose-related differences. IDO-1 inhibitors failed to improve outcomes compared with standard ICI. Reporting quality varied, with concerns regarding incomplete outcome data in some trials.

    Conclusion: These findings suggest promise for novel ICIs but are limited by small study numbers, methodological bias, and clinical heterogeneity. Larger, well-designed Phase III trials are required to validate these results.

  • research-article
    Malefo Tshepiso Mofokeng, Rahul Chandran, Heidi Abrahamse

    Due to its multifaceted nature, cancer remains a formidable disease that continues to cause substantial mortality globally. Conventional treatments, such as surgery, chemotherapy, and radiation therapy, often fail to adequately control this aggressive disease, thereby reducing the quality of life of affected individuals. Photodynamic therapy (PDT) has emerged as a promising treatment modality that utilizes lasers to destroy cancer cells. While PDT has shown promise as a safer and more targeted treatment with fewer side effects compared to some conventional therapies, it faces certain limitations, such as limited light penetration for deep tumors and the need for tissue oxygenation in hypoxic regions. The emergence and potential use of artificial intelligence (AI)-driven technologies in PDT may offer favorable outcomes for cancer treatment by addressing some of the limitations of conventional PDT. AI uses machine learning (ML) and deep learning (DL) algorithms to continuously learn, adapt to changes, recognize abnormalities in a dataset, and make accurate predictions. In this review, we propose integrating AI tools, such as ML and DL, with PDT to combat cancer and address some of the limitations of conventional PDT. The combination of AI and PDT could improve the precision and effectiveness of PDT for cancer treatment by monitoring the effects of PDT during treatment, advancing imaging techniques for better diagnosis of specific tumor types, enabling monitoring of light in real time, and overcoming light-delivery limitations associated with deep, internal tumors, with the potential to improve overall clinical outcomes in cancer patients.

  • research-article
    Lunzhi Liu, Ao Wang, Ke Yi

    Introduction : The association between mitochondrial DNA (mtDNA) copy number and hypertensive disorders in pregnancy has been explored in several observational studies; however, due to methodological limitations and confounding factors, consistent conclusions have not been reached.

    Objectives: This study aimed to determine whether genetically predicted mtDNA copy number has a causal effect on the risk of hypertensive disorders in pregnancy using Mendelian randomization (MR) analysis.

    Methods : MR analyses were performed to assess genetic relationships and potential causal associations among four hypertensive pregnancy outcomes: Pre-existing hypertension complicating pregnancy, gestational hypertension, pre-eclampsia or eclampsia (POE), and pre-eclampsia (PE). The mtDNA copy number for each outcome was obtained from genome-wide association study datasets. The primary MR method was inverse variance weighting (IVW), supported by four complementary approaches (MR-Egger, weighted median, simple mode, and weighted mode) to ensure robust inference.

    Results : IVW analysis revealed a significant inverse correlation between mtDNA copy number and both POE (odds ratio [OR] 95% confidence interval [CI] = 0.738 [0.578 – 0.943];p =0.015) and PE (OR [95% CI] = 0.735 [0.563 – 0.960];p =0.024), suggesting a protective effect of higher mtDNA copy number.

    Conclusion : This MR investigation demonstrates a positive causal relationship between higher mtDNA copy number and reduced risk of PE and related hypertensive disorders in pregnancy.

  • research-article
    Long Guo, Yan Zhang, Jun Liu, Xiaodan Li, Wende Li, Yanwen Liang, Wenjing Cheng, Hua Ye, Yi Liu

    Introduction: Prognosis and treatment outcomes of colon cancer (CC) patients are poor due to the limitations of the current early diagnostic techniques. Recently, innovations in liquid biopsy technology have inspired research into identifying early peripheral blood-based diagnostic markers for CC.

    Objective: The objectives of the study are to evaluate the potential of plasma miR-378a as a diagnostic biomarker for early CC.

    Methods: In this study, quantitative reverse transcription polymerase chain reaction was used to measure plasma miR-378a levels in CC patients, patients with colon polyps (CPs), and healthy controls (HCs). The study included 94 CC patients (56 males, 38 females; age range 35 – 82 years, mean age 57.7 ± 10.1 years) and 65 patients with CPs (40 males, 25 females; age range 42 – 91 years, mean age 63.0 ± 11.4 years), including 24 adenomatous polyps, 15 inflammatory polyps, 12 hamartomatous polyps, 14 hyperplastic polyps, and 45 HCs. The correlation between miR-378a and clinicopathology features was analyzed, and diagnostic value of miR-378a in each group was assessed using receiver operating characteristic (ROC) curve analysis.

    Results: CC patients had significantly lower plasma miR-378a levels compared to patients with CPs (p <0.0001) and HCs ( p =0.0018). miR-378a levels were significantly correlated with TNM stage, tumor size, and lymph node metastasis (p <0.05). ROC curve analysis illustrated strong diagnostic discriminative power of miR-378a for CC and CPs, with an area under the curve of 0.8202 (95% confidence interval: 0.7528 – 0.8876), sensitivity of 89.36%, and specificity of 66.15%.

    Conclusion: These findings suggest that plasma miR-378a may serve as a potential biomarker for early diagnosis of CC.

  • research-article
    Jianfeng Zhang, Hongyan Duan, Jie Zhang, Mengchen Ji, Xia Shen, Yueqin Ni

    Introduction: Patients with liver cancer frequently receive multiple transcatheter arterial chemoembolization (TACE) treatments. While some studies have investigated the symptoms and symptom clusters that occur following TACE, there is limited understanding of the core symptoms and symptom clusters experienced during the intervals between TACE treatments.

    Objective: This study aims to identify core symptoms and symptom clusters in patients with primary hepatocellular carcinoma (HCC) during the intermittent period of TACE, providing a reference for precise symptom management.

    Methods: A convenience sample of 344 patients undergoing intermittent TACE was recruited. Symptom prevalence and severity were evaluated using the Chinese version of the MD Anderson symptom inventory and the HCC-specific symptom module. Principal component analysis was used to extract symptom clusters. A symptom network was constructed to illustrate inter-symptom relationships and to calculate centrality indices.

    Results: Four symptom clusters were identified: upper gastrointestinal, feeling of illness, emotional-psychological, and liver function impairment. Lack of appetite demonstrated the highest strength ( rs = 1.10) and closeness (rc = 0.0076) centrality in the symptom network. The strongest marginal association was found between distress and sadness (r = 0.545).

    Conclusion: Lack of appetite emerged as the core symptom, while the emotional–psychological cluster was the core symptom cluster. Nursing interventions should prioritize addressing appetite loss and managing emotional symptoms such as distress and sadness to enhance the effectiveness of symptom management during the intermittent period of TACE in patients with primary HCC.

  • research-article
    Xiangbing Zheng, Zhengqiang Wan, Bing Liu, Jun Yin, Cheng Chen, Yuzhen Ma, Yong Zou

    Introduction: Keloid, a fibroproliferative tumor characterized by excessive collagen deposition and fibroblast hyperplasia, lacks effective therapeutic strategies due to unclear molecular mechanisms.

    Objective: This study aims to elucidate keloid pathogenesis and identify diagnostic biomarkers through multi-omics integration.

    Methods: Single-cell RNA sequencing (ScRNA-seq) data (GSE163973) and bulk RNA sequencing datasets (GSE162904/GSE145725) were analyzed. Fibroblast subpopulations were identified using the Seurat R package, and cell–cell interactions were explored using the CellChat R package. Weighted gene co-expression network analysis (WGCNA) was employed to identify key gene modules in fibroblasts. Hub genes were screened using Lasso regression and validated through machine learning algorithms and a gene-immune convolutional neural network (CNN). Immune infiltration patterns were evaluated using the MCP-counter and Immuno-Oncology Biological Research R packages.

    Results: ScRNA-seq analysis revealed eight distinct cell subtypes within keloid tissues, with fibroblasts significantly enriched compared to normal skin. Fibroblast clusters 1 and 5 exhibited elevated midkine–low-density lipoprotein receptor-related protein 1-mediated interactions and enhanced differentiation activity. WGCNA identified three critical modules-“brown,” “cyan,” and “yellow”-linked to fibroblast activation. Lasso regression produced an eight-gene signature that effectively distinguished keloid from normal skin (area under the curve = 0.885 – 0.889). Nonnegative matrix factorization classified keloids into four subtypes, each with distinct immune infiltration profiles correlated with hub gene expression. The gene-immune CNN model achieved 100% sensitivity and 88.9% specificity in diagnostic classification.

    Conclusion: This study elucidates the molecular mechanisms underlying keloid formation through integrated single-cell and transcriptomic analysis, proposing an eight-gene signature as a potential diagnostic and therapeutic target. The identified keloid subtypes and associated immune infiltration patterns provide novel insights for advancing precision medicine approaches in keloid management.

  • research-article
    Kexin Liu, Xiaoyu Huang, Ping Li, Ting Wang, Ting Sun

    Introduction: RAS wild-type (WT) is the most common genotype in colorectal cancer (CRC). In recent years, an increasing number of researchers have focused on the pathogenesis, clinical features, and treatment strategies of RAS WT CRC.

    Objective: This study aims to provide a comprehensive analysis of the current state of research in the field, including key research trends and intricate networks of collaborations.

    Methods: Literature on RAS WT CRC was retrieved from the Web Of Science core collection (2009 – 2022). Using CiteSpace (v6.1.R6) and VOSviewer (v1.6.18), we analyzed 495 publications from 57 countries/regions, 368 institutions, and 426 authors.

    Results: According to statistics, the country with the most publications on this topic is Italy ( n = 118, 23.8%), followed by the United States ( n = 105, 21.2%), Germany ( n = 90, 18.2%), and China ( n = 79, 16.0%). S. Stintzing ( n = 26) has the highest number of publications, while E. Van Cutsem ( n = 306) has the highest number of citations. Istituto di Ricovero e Cura a Carattere Scientifico was the main publishing institution in this field, Clinical CRC was the most important publication journal, and Journal of Clinical Oncology was the most cited journal in the field ( n = 442). Chemotherapy, first-line treatment, metastatic CRC, acquired resistance, cetuximab, and bevacizumab were among the popular keywords in the field of RAS WT CRC. The current frontier research topics in this field include “plus bevacizumab,” “elderly patient,” and “primary tumor.”

    Conclusion: Over the past decade, research on RAS WT CRC has continued to grow, reflecting the sustained attention and investment of the academic community. Italy, Germany and the United States, which had the highest number of publications, were found to maintain close international collaborative networks. The current research landscape focuses on novel methods and applications of targeted drugs for treating RAS WT CRC, such as tailoring treatment regimens according to the location of the primary tumor and introducing targeted drugs.

  • research-article
    Ke Ren, Xin Gou, Weiyang He

    Introduction: Hormone-sensitive prostate cancer typically progresses to a castration-resistant stage after an average of 18–24 months of androgen deprivation therapy (ADT). The anti-apoptotic factor X-linked inhibitor of apoptosis protein (XIAP) is not only implicated in the development of prostate cancer but also plays a critical role in its progression to the castration-resistant state.

    Objective: This study aims to investigate the relationship between ADT and the regulation of XIAP.

    Methods: The protein expression levels of midline 1 (MID1), serine/threonine kinase proviral integration site for Moloney murine leukemia virus 2 (PIM2), protein phosphatase 2A (PP2A), eukaryotic translation initiation factor 4B (EIF4B), phosphorylated EIF4B, and XIAP were analyzed and compared among castration-naïve, hormone-sensitive, and castration-resistant prostate cancer (CRPC) tissues. The MID1 gene was manipulated in both androgen-dependent and androgen-independent prostate cancer cells to evaluate its effect on XIAP protein expression and the apoptosis rate of the prostate cancer cells.

    Results: XIAP protein expression and EIF4B phosphorylation levels were significantly increased in CRPC. In contrast, PIM2 and EIF4B protein expression levels remained similar before and after the development of castration resistance. MID1 protein expression level was significantly elevated, while PP2A expression was significantly reduced in CRPC tissues.

    Conclusion: ADT may lead to elevated MID1 and reduced PP2A protein expression levels, which indirectly enhance the phosphorylation activity of PIM2 on EIF4B, thereby increasing XIAP expression and reducing apoptosis in prostate cancer cells. This mechanism likely contributes to disease progression toward the castration-resistant stage.

  • research-article
    Xulong Zhu, Xinmiao Liu, Ziyu Luo, Shuhan Wu, Hengtao Song, Ke Yan, Yue Wang, Liping Yang, Wenjun Shu, Kenian Pan, Jianhui Li

    Introduction: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is characterized by increased cell proliferation and a high potential for metastasis, resulting in a poorer prognosis–especially when brain metastases occur. At present, no definitive clinical factors or predictive models exist to guide prognosis in this patient group

    Objective: This study aims to identify prognostic factors affecting survival in HER-2 breast cancer patients with brain metastases and to construct a model to assess prognosis based on clinical characteristics.

    Methods: Data from female patients diagnosed with breast cancer brain metastases between 2011 and 2020 were extracted from the Surveillance, Epidemiology, and End Results database. Seventeen clinical factors were evaluated for their association with brain metastasis in HER2-positive breast cancer. Univariate and multivariate Cox proportional hazard regression analyses were performed, and Kaplan-Meier survival curves were plotted based on independent risk factors. A nomogram model was then developed to predict survival rates at different time intervals. Model performance was evaluated using calibration curves and the concordance index. Receiver operating characteristic analysis and decision curve analysis (DCA) were also conducted to evaluate predictive accuracy and clinical utility.

    Results: Cox regression analyses identified nine clinical characteristics significantly associated with overall survival (OS) and seven factors influencing breast cancer-specific survival: molecular subtype, age, node stage, liver and lung metastases, and estrogen receptor and progesterone receptor status. The models achieved concordance indices of 0.680 (OS) and 0.663 (breast cancer-specific survival). The nomogram demonstrated strong predictive power, with area under the curve values of 0.767 and 0.700, respectively. DCA showed that the model curve significantly outperformed the two extreme curves.

    Conclusion: This study identified key prognostic factors and developed a nomogram-based model with strong predictive value for HER2-positive breast cancer patients with brain metastases.

  • research-article
    Yufeng Li, Zhipeng Wei, Yifan Xu

    Introduction: Lung adenocarcinoma (LUAD) exhibits significant genomic heterogeneity, with SMARCA4 mutations often co-occurring with other mutated genes that may shape disease progression and patient outcomes.

    Objective: The objective of the study is to investigate the impact of co-mutated genes on the prognosis and immunotherapeutic response in SMARCA4 -mutant LUAD.

    Methods: Genomic and clinical data from SMARCA4 -mutant LUAD patients were extracted from the Memorial Sloan Kettering cohort through cBioPortal, with overall survival (OS) as the primary endpoint. We systematically assessed the most frequent coexisting genomic alterations.

    Results: Within a cohort of 5,957 LUAD patients, we identified 8% ( n = 477) harboring SMARCA4 mutations. The most frequent co-mutations included TP53 ( 49%), STK11 ( 48%), KEAP1 ( 46%), KRAS (39%), and CDKN2A (33%). TP53 co-mutations exhibited significant mutual exclusivity with STK11 , KEAP1 , KRAS , and CDKN2A . Multivariable analysis revealed that KRAS , STK11 , and KEAP1 co-mutations independently predicted shortened survival, whereas CDKN2A and TP53 co-mutation status showed no significant prognostic impact. Notably, TP53 co-mutations were associated with elevated tumor mutational burden and higher programmed death-ligand 1 expression. In Stage IV SMARCA4 -mutant LUAD patients, an improved prognosis associated with co-mutation of TP53 and KRAS was observed with immune checkpoint inhibitor therapy.

    Conclusion: In SMARCA4 -mutant LUAD patients, TP53 , STK11 , KEAP1 , KRAS , and CDKN2A were the most frequent co-occurring genomic alterations. Multivariable analysis identified KRAS , STK11 , and KEAP1 co-mutations as independent adverse prognostic factors. Notably, tumors harboring STK11 / KEAP1 double mutations or KRAS / STK11 / KEAP1 triple mutations exhibited extremely poor OS, whereas TP53 co-mutations correlated with favorable outcomes and significant immunotherapy benefit. Intriguingly, TP53 mutations demonstrated mutual exclusivity with KRAS , STK11 , and KEAP1 alterations, suggesting divergent oncogenic trajectories.

  • research-article
    Hui Liu, Somchai Bovornkitti, Sarisak Soontornchai, Xiaoqiang Qiu, Wenjie Shi

    Introduction: Inflammatory responses play an essential role in metabolic dysfunction-associated steatotic liver disease (MASLD).

    Objective: This study investigates the mediating role of systemic inflammation in the pathophysiology of heavy metal-induced MASLD.

    Methods: We employed data from the National Health and Nutrition Examination Survey from 2017 to 2020 to examine the relationship between 16 heavy metals and MASLD. Vibration-controlled transient elastography was used to evaluate hepatic steatosis and determine the Systemic Immune Inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI). Data analysis was conducted using linear or logistic regressions, weighted quantile sum regression (WQS), restricted cubic spline, and mediation effect models.

    Results: The study involved 2,934 patients, with an average age of 44.86 ± 20.58 years, of whom 50.23% were female. Urinary cadmium (Cd), lead (Pb), arsenic, mercury, and tungsten were all positively associated with MASLD risk. The WQS model showed a strong positive correlation between a high amount of urea-metal mixtures and higher SII, SIRI, and MASLD (p <0.01). Mediation analysis found that systemic inflammation mediated the effects of single metals (Cd, cesium [Cs], and Pb) on MASLD risk. The mediation proportions of urinary metal mixtures on MASLD risk, mediated by SII and SIRI, were 57.84% and 65.21%, respectively.

    Conclusion: Based on the findings, systemic inflammation partially mediates the association between metals such as Cd, Cs, and Pb-and their combined effects-and metabolic dysfunction and steatosis. Hence, reducing systemic inflammation could help prevent and treat metal-related steatohepatitis caused by environmental exposure.

  • research-article
    Meryem Saban Güler, Saniye Bilici, Hakan Bulak

    Introduction: Malnutrition is a common yet frequently underdiagnosed complication in cancer patients and is strongly associated with poor prognosis. Early identification through accurate screening and comprehensive nutritional assessment is essential for improving nutritional status and quality of life.

    Objective: The objective of this study was to evaluate the nutritional status of adult cancer patients using the Patient-Generated Subjective Global Assessment (PG-SGA) in combination with anthropometric, biochemical, and dietary parameters.

    Methods: This cross-sectional study assessed the nutritional status of 279 adult cancer outpatients using the PG-SGA, supplemented by medical and dietary histories, physical examinations, anthropometric measurements, and laboratory parameters.

    Results: According to PG-SGA scores, 31.3% of men and 12.6% of women were classified as severely malnourished. Anthropometric values showed a significant decline across PG-SGA categories, from well-nourished (PG-SGA-A) to severely malnourished (PG-SGA-C) patients ( p <0.05). Serum albumin, total protein, hemoglobin, and total cholesterol levels were significantly higher in PG-SGA-A patients, whereas C-reactive protein was elevated in PG-SGA-C patients ( p <0.05). Analysis of nutrient intake revealed higher consumption of fiber, fat, saturated fat, and cholesterol among PG-SGA-A patients compared with PG-SGA-C patients ( p <0.05). Body weight, body mass index, mid-upper arm circumference, triceps skinfold thickness, mid-upper arm muscle area, mid-upper arm muscle circumference, and lean body mass were all negatively correlated with malnutrition severity ( p <0.05).

    Conclusion: These findings confirm the high prevalence of malnutrition in oncology outpatients and underscore the importance of integrating both subjective and objective tools for early detection and timely management of malnutrition in cancer care.

  • research-article
    Federico Ruta, Sipontina Rita Zerulo, Roberta Di Matteo, Sabrina Cannone, Francesca Dal Mas, Paolo Ferrara, Tatiana Bolgeo, Mauro Parozzi, Giovanni Cangelosi, Stefano Mancin, Alice Masini, Gabriele Caggianelli

    Introduction: Advances in pediatric oncology have increased survival rates of patients. To support the long-term care of these survivors, the Survivorship Passport (SurPass) provides a personalized, portable summary of their diagnosis, treatments, and potential sequelae.

    Objective: This study investigates the correlation between SurPass use and long-term knowledge gains among survivors, as measured by its impact on the accuracy of treatment recall and awareness of potential long-term effects.

    Methods: This observational study included long-term survivors classified into two arms: Those with SurPass (Arm A) and those without (Arm B). A structured questionnaire assessed recall of diagnosis, chemotherapy, radiotherapy, and awareness of late effects. Responses were scored for accuracy, and between-group comparisons were performed.

    Results:Survivors with SurPass, who are typically followed up in specialized centers, demonstrated markedly higher recall accuracy than those without it. Correct recollection of radiotherapy and chemotherapy was higher in Arm A by 64% (p=0.05) and 48% (p=0.03), respectively. Awareness of late effects and adherence to structured follow-up were also greater within Arm A. The SurPass mitigated the expected decline in recall accuracy over time, particularly for survivors treated at younger ages.

    Conclusion: Preliminary findings suggest that SurPass may support patient engagement and continuity of care in survivorship settings; however, longitudinal studies are needed to confirm these exploratory findings.

  • research-article
    Zijiao Li, Yinli Su, Liying Qin, Han Wu, Wan Fu, Xinyu Wang, Longyang Li, Xuerou Wang, Di Chen, Ya Xie, Linlin Li

    Introduction: PIK3CA mutations are prevalent in ovarian cancer (OC) and drive cancer progression by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Sulforaphane (SFN), a natural compound derived from cruciferous vegetables, exhibits antitumor effects; however, its specific mechanisms, especially those related to metabolic reprogramming in PIK3CA-mutated cancers, remain unclear.

    Objective: This study investigates the alterations in glucose metabolism and the selective inhibitory effects of SFN in PIK3CA-mutated OC cells.

    Methods: Clinical samples from OC patients were analyzed to determine PIK3CA mutation status and its prognostic relevance to patient outcome. PIK3CA-mutated and wild-type OC cell lines were used for in vitro analysis. Glycolysis and mitochondrial respiration were assessed using the Seahorse XF Analyzer. Gene and protein expression were analyzed through RNA sequencing, real-time quantitative polymerase chain reaction, and Western blotting. Metabolite levels were m-easured through untargeted mass spectrometry. The effects of SFN were validated in vitro and in a mouse xenograft model.

    Results: PIK3CA mutations were associated with poorer progression-free survival in OC patients. PIK3CA-mutated OC cells exhibited enhanced glycolysis and tricarboxylic acid (TCA) cycle activity compared to wild-type cells. SFN selectively inhibited the proliferation of PIK3CA-mutated cells by suppressing glycolysis and the TCA cycle, downregulating key glycolytic enzymes (e.g., hexokinase 1 and 2) and reducing TCA cycle intermediates (e.g., α-ketoglutaric acid and citrate). Mechanistically, SFN inhibited the PI3K/Akt pathway, resulting in reduced Akt phosphorylation. In vivo, SFN more effectively inhibited tumor growth in mice bearing PIK3CA-mutated xenografts.

    Conclusion: PIK3CA mutations enhance both glycolysis and the TCA cycle in OC. SFN selectively inhibits the growth of PIK3CA-mutated OC cells by targeting the PI3K/Akt pathway, leading to the suppression of glucose metabolism. These findings highlight the therapeutic potential of SFN for PIK3CA-mutated OC.

  • research-article
    Kristina Bliznakova, Radoslav Georgiev, Zhivko Bliznakov

    Introduction: Lumbar spine magnetic resonance imaging (MRI) is a high-volume diagnostic examination, yet increasing caseloads and reporting complexity continue to strain radiology workflows. Emerging artificial intelligence (AI)-assisted reading tools may help streamline interpretation and reduce report turnaround times, but their real-world impact on efficiency remains insufficiently quantified.

    Objective: To evaluate the impact of an AI-based reading tool on lumbar spine MRI interpretation and reporting time.

    Methods: We randomly selected 236 lumbar spine MRI examinations performed between 2018 and 2023 in patients aged 18 and older. Cases with prior lumbar surgery or scoliosis were excluded. Digital imaging and communications in medicine (DICOM) data were processed using a commercial deep-learning software package, and outputs were reviewed in a standard DICOM viewer. Five radiologists participated. Studies 1 and 2 assessed the effect of AI on interpretation time using a within-reader design: radiologists interpreted each examination with AI support and then reinterpreted the same examinations 2 months later without AI, enabling direct comparison of interpretation times. Study 3 evaluated the effect of AI by comparing AI-assisted and unassisted interpretations in 146 randomly selected examinations.

    Results: AI assistance significantly accelerated report generation. Across the full dataset, AI-supported interpretation reduced time by approximately 52% compared with unassisted reading. AI-assisted generation of preliminary reports reduced radiologists’ overall time by nearly 30%. Linear mixed-effects modeling indicated that these reductions were statistically significant. The smaller reduction observed in Study 3 (9.21%) may reflect limited familiarity with the software’s reporting style and occasional instances in which the AI outputs did not fully support the radiologists’ findings.

    Conclusion: AI assistance improves the efficiency of lumbar spine MRI reporting and shortens reporting time.

  • research-article
    Mattia Morri, Felicia Iacovone, Cristiana Forni, Grazia Lisciandrello, Francesca Corvino, Davide Maria Donati, Daniela Di Nicolantonio

    Introduction: Distress is common among cancer patients, especially in orthopedic oncology, but its perioperative course remains insufficiently explored

    Objective: This study aimed, first, to describe the emotional distress experienced by patients with benign and malignant bone and soft-tissue tumors before orthopedic oncologic surgery and, second, to examine how the level of distress varied during hospitalization.

    Methods: A retrospective observational study was performed, and patients admitted to the orthopedic oncology department were enrolled. Distress was recorded before and after surgery. A reduction of at least one point in the Distress Thermometer (DT) score was considered an improvement. Potential causes of distress were systematically documented. Data required for the study were extracted from patients’ medical records by a research nurse.

    Results: During the study period, 319 patients were screened, of whom 119 were included in the analysis. The mean DT score was 5.2 at admission and 4.3 at discharge, with a statistically significant difference of 0.9 (95% confidence interval: 0.4–1.5; p <0.001). Pain was the main reported cause of distress at both admission and discharge. The presence of distress at admission, shorter duration of hospitalization, and receipt of psychological support were associated with a decrease in distress.

    Conclusion: Perioperative distress in patients undergoing orthopedic oncologic surgery must be carefully monitored in clinical practice. Pre- to postoperative distress showed a favorable trajectory, with a significant reduction observed. Pain and emotional problems were identified as the main sources of distress, though with different trajectories: increasing for pain and decreasing for anxiety. Targeted pain management and psychological support pathways should be encouraged for these patients.

  • research-article
    Wang Ting, Salwismawati Badrin, Salziyan Badrin

    Introduction: Cancer patients often experience psychological distress that accompanies their physical symptoms; consequently, heightened spiritual needs may reflect an important coping response. In Chinese cultural settings, the manifestation of spirituality is significantly different from that suggested by Western paradigms, with greater emphasis on non-religious aspects of spirituality, including harmony between people and inner peace, than on traditional religious beliefs.

    Objective: The current study aims to assess the spiritual needs of Chinese cancer patients in the hospital and to define sociodemographic, psychological, and clinical variables correlated with these needs using Chinese-validated instruments.

    Methods: A cross-sectional study was conducted between February and April 2025, involving 189 cancer patients who presented to Shanxi Bethune Hospital in China. Participants were requested to complete the Chinese version of the 27-item Spiritual Needs Questionnaire (SpNQ-Ch-27), the Patient Health Questionnaire-9, and the Multidimensional Scale of Perceived Social Support. The data were analyzed using descriptive statistics, correlation analyses, and multiple linear regression.

    Results: Participants reported moderate spiritual needs, with an average SpNQ-Ch-27 overall score of 37.23 (standard deviation = 16.91). The highest scores were obtained in the domains of active giving and inner peace, and the lowest in the religious domains, indicating a prevalence of a non-religious spiritual orientation. The predictors of spiritual needs identified using multivariate regression included a time since diagnosis of <6 months ( β = 0.52, p <0.001), greater severity of depressive symptoms ( β = 0.21, p =0.002), rural residence ( β = 0.19, p =0.003), and low household income <3,000 RMB/month), which also showed a significant negative association ( β = −0.14, p =0.029). The final model explained 78.9% of the variance in spiritual-needs scores.

    Conclusion: Recently diagnosed cancer patients demonstrate the highest spiritual needs, with depression and socioeconomic vulnerability serving as additional risk factors. Chinese patients prioritize relational and existential spiritual dimensions over religious practices.

  • research-article
    Mattia Morri, Marco Cotti, Riccardo Ruisi, Pietro Cimatti, Davide Maria Donati

    Introduction: Evidence on early functional recovery and inpatient physiotherapy after lower limb salvage surgery for bone sarcomas is limited

    Objective: This study aims to describe early ambulation and explore potential prognostic factors.

    Methods: A retrospective cohort study was conducted, including patients aged 12–70 years with bone and soft-tissue sarcoma who underwent lower limb resection and reconstruction between 2019 and 2023. The primary outcome was time to ambulation, and the secondary outcome was length of hospital stay.

    Results: A total of 84 patients were included in this study. The median time to ambulation was 4 post-operative days (interquartile range [IQR], 4), and the median length of stay was 8 (IQR, 4). In multivariable Cox regression, earlier ambulation was associated with tumor location in the diaphysis/other sites (hazard ratio [HR] = 4.39, p =0.002), older age (HR = 1.02 per year, p =0.006), and higher physiotherapy intensity when initiated on post-operative day 1 (HR = 1.74, p =0.001). Bone graft/other procedures were associated with a lower hazard of ambulation compared with prosthetic reconstruction (HR 0.46, p =0.037). Each additional day of ambulation was associated with a 12% lower hazard of discharge (HR = 0.88, p =0.009).

    Conclusion: Early mobilization and intensive physiotherapy appear to facilitate functional recovery following lower limb salvage surgery for bone and soft-tissue sarcomas. These findings emphasize the value of structured, staff-led rehabilitation programs that actively encourage and guide recovery, highlighting the role of clinical staff in optimizing post-operative outcomes and may improve patients’ independence.

  • research-article
    Arash Moradi, Seyedeh Hanieh Safavi Komamardakhi, Ramtin Mohammadi, Majid Pornour, Azar Heidarizadi, Mahmoud Hatami, Mariasanta Napolitano, Shahla Mohammad Ganji

    Introduction: Colorectal cancer (CRC) is a leading cause of cancer mortality. MicroRNAs are key regulators of gene expression implicated in carcinogenesis. While miR-182 is an established oncomiR and miR-490 acts as a tumor suppressor, the prognostic significance of their mature arms (−3p/−5p) remains unclear.

    Objective: This study aims to validate these mature arms in CRC and assess their association with 5-year overall survival.

    Methods: We combined bioinformatics with experimental validation in 48 CRC patients. Putative targets were analyzed for their involvement in biological pathways. Expression levels were quantified in tumor and paired normal tissues using quantitative PCR. Associations with survival were evaluated using Kaplan–Meier and Cox proportional hazards models.

    Results: Bioinformatics linked miR-182 targets to cell movement and miR-490 to the mitotic cell cycle. In patient tissues, miR-182-5p (fold change [FC]: 16.19) and miR-182-3p (FC: 3.38) were significantly upregulated ( p <0.05). Conversely, miR-490-5p (FC: 0.26) and miR-490-3p (FC: 0.76) were significantly downregulated ( p <0.05). Despite this dysregulation, multivariate Cox models showed no significant association with 5-year survival. Hazard ratios (HR) lacked significance for both miR-182-5p (HR = 0.858, 95% CI: 0.610–1.205, p =0.377) and miR-490-3p (HR = 0.665, 95% CI: 0.357–1.239, p =0.198).

    Conclusion: This study validates the opposing dysregulation of mature miR-182 and miR-490 arms in CRC, reinforcing their respective oncogenic and tumor-suppressive roles. However, these profound expression changes did not translate into prognostic utility for 5-year survival in this cohort, suggesting that larger high-throughput-based studies are required to detect putative prognostic effects.

  • research-article
    Raditya Wratsangka, Monica D. Hartanti, Gatot Purwoto, Lily M. Surjadi, Miranti P. Aulia, Alvionita Kogoya

    Introduction: Cervical cancer continues to pose a substantial worldwide health challenge, primarily linked to human papillomavirus (HPV) infection. In regions like Indonesia, understanding local genotype distribution is critical for refining screening and vaccination efforts.

    Objective: This research explores the complex relationship between various risk factors and the types of HPV detected in cervical cancer patients at a national referral center in Indonesia.

    Methods: Ninety-one women diagnosed with cervical cancer were recruited for this cross-sectional study at Cipto Mangunkusumo National Hospital, Jakarta-the top-tier referral facility in Indonesia. This setting provides a diverse patient demographic representing various geographical regions across the archipelago. Cervical swabs were collected for HPV genotyping using dot blot hybridization. Various clinical risk factors, including age, age at marriage, age at first pregnancy, parity, smoking habits, hormonal contraceptive history, and the stage of cervical cancer diagnosis, were assessed. Statistical analysis was conducted using Fisher’s exact test to accommodate the distribution of the data.

    Results: High-risk (HR) HPV was detected in 62.6% of participants. HPV type 18 was the most prevalent (15.4%), followed by types 52 (14.3%) and 16 (12.1%). Statistically significant associations were observed between HR-HPV presence and both early age at marriage (p = 0.004) and the use of hormonal contraception (p = 0.002). No significant correlations were observed between some patient characteristics (age, parity, and smoking habits) and HPV genotypes (p > 0.05). A total of 35.2% of samples were HPV-negative, potentially reflecting technical challenges or viral integration in advanced-stage cases.

    Conclusion: These findings suggest that early marriage and hormonal contraceptive use are significant clinical markers for HR-HPV in this Indonesian population. The dominance of HPV 18 and 52 highlights the need for locally relevant diagnostic tools and the potential transition to nonavalent vaccines. These data are essential for developing locally relevant diagnostic tools and optimizing cervical cancer prevention strategies tailored to the Indonesian demographic.

  • research-article
    Dhona Afriza, Utmi Arma, Hana Azzahra, Alimuddin Tofrizal

    Introduction: Materials based on polymethyl methacrylate (PMMA) have become more widely used because of their many benefits in various medical specialties, such as maxillofacial surgery, ophthalmology, and orthopedic prostheses. Since methyl methacrylate (MMA), the monomer from which PMMA is made, is extremely volatile and breathed during handling, inhalation is the main way that laboratory and healthcare workers are exposed to MMA. This compound is toxic and can irritate the respiratory mucosa, respiratory system, skin, nervous system, and other organs

    Objective: This study aims to assess the effect of MMA inhalation on lung tissue histology.

    Methods: This in vivo experimental study used 15 white mice, which were randomly assigned to three groups: A negative control, a group exposed to MMA for 1 week, and a group exposed for 3 weeks. Mice were subjected to MMA inhalation for 6 h/day. Following exposure, lung tissues were processed for histological examination, including fixation, dehydration, paraffin embedding, sectioning, and hematoxylin-eosin staining. Lung injury was evaluated using a semi-quantitative histological scoring system and by measuring alveolar diameter in five fields of view.

    Results: No lung damage was observed in the control group; lung histology remained within normal limits. The group exposed to MMA for 1 week showed mild to moderate lung damage, whereas the group exposed for 3 weeks exhibited moderate to severe histological damage. Measurements of alveolar diameter showed a decrease in both MMA-exposed groups.

    Conclusion: Inhalation exposure to MMA causes significant histological damage to lung tissue in mice.

  • research-article
    Anna Skotny, Paulina Podlawska-Nowak

    Introduction: Access to oncology care in Poland remains uneven, with rural residents limited to specialist availability. We analyzed geographic factors that may worsen cancer outcomes and deepen health disparities in Poland between rural and urban inhabitants. Objectives: This study aims to evaluate the impact of geographic and demographic factors on cancer diagnosis in central Poland, focusing on disparities between urban and rural populations.

    Methods: A retrospective cohort analysis was conducted on 4,771 patients suspected of having cancer at the Nikolay Pirogov Specialized District Hospital in Łódź between 2020 and 2024. Clinical records and public health datasets were analyzed. Logistic regression was used to assess associations between cancer diagnosis and variables such as distance to the nearest hospital, residence type (urban vs. rural), age, and sex. Models were adjusted for potential confounders.

    Results: Of the 4,771 patients evaluated, 2,996 (62.8%) received a cancer diagnosis and 1,775 (37.2%) did not. In multivariable models, living 5–10 km from the hospital (vs. <5 km) was associated with higher odds of confirmed diagnosis, while residence types were not independently associated with diagnosis. We explicitly limited inference to individuals who ultimately accessed hospital care.

    Conclusion: Geographic accessibility showed a localized association within the 5–10 km band, whereas residence >10 km and urban/rural status did not demonstrate independent effects after adjustment. These findings are hypothesis-generating and should be interpreted as indicators of potential access pathways among hospital-admitted patients, rather than causal effects. Targeted interventions (e.g., mobile diagnostics, transportation support, and optimized referral pathways) warrant evaluation.

  • research-article
    Graziella Di Grezia, Teresa Iannaccone, Valentina Giudice