Medical sciences (Basel, Switzerland)最新文献

Background: The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), an enzyme essential for metabolising chemotherapeutic agents such as capecitabine, 5-fluorouracil (5-FU), and tegafur. Variants in this gene can increase the toxicity of these treatments. Methods: This study analysed data from 1478 cancer patients at Nottingham University Hospitals who received chemotherapy between December 2021 and December 2023. The study assessed the prevalence of DPYD variants across different tumour types, ethnic groups, and socioeconomic factors. Results: Overall, DPYD variants were identified in 7% of patients, with higher rates in colorectal cancer (7.9%) and among Caucasian patients (7.4%). The most frequent variant was c.1129-5923C>G (HapB3), found in 75.7% of variant-positive cases. No significant differences in DPYD testing rates were observed across socioeconomic groups or between ethnic backgrounds within our cohort. Conclusions:DPYD variants were prevalent in 7% of the cohort, and testing access was not influenced by socioeconomic status.

Background: Sarcomas are rare, aggressive malignancies with limited therapeutic options in advanced stages. This is the first real-world study in the MENA region evaluating the clinical utility of Next-Generation Sequencing (NGS) in guiding sarcoma treatment and improving outcomes. Methods: We retrospectively reviewed sarcoma patients who underwent NGS at a major referral center (2021-2024), comparing clinical and molecular outcomes between those who received NGS-based treatment adjustments (NBTA) and those who did not. Results: Seventy-eight patients were included (60% male; median age 44 years). Soft tissue sarcomas accounted for 70.5% of cases (n = 55), while bone sarcomas represented 29.5% (n = 23). Prior to NGS, 64.1% of patients had received a median of one line of systemic therapy. NGS was performed late in the disease course in 73% of cases. At least one mutation was detected in 87% (median 3 mutations). Targetable alterations were identified in 33% at the time of testing, rising to 42% with updated genomic knowledge and therapeutic advances. Overall, 20.5% received NBTA. Among non-NBTA patients, 67% had no actionable targets, 17% had no detectable mutations, and 16% were ineligible due to cost, limited access, or clinical deterioration. Tumor Mutational Burden was low in 79%, intermediate in 19%, and high in 2%, and all tumors were microsatellite stable. Patients receiving NBTA had a longer median Progression-Free Survival (9 vs. 2 months; p = 0.023). Median Overall Survival was longer in the NBTA group (74 vs. 48 months), though not statistically significant (p = 0.207). Genomic alterations were subtype-specific: EWSR1 rearrangements (Ewing and Desmoplastic small round cell tumors), CDK4 and MDM2 amplifications (Liposarcoma and Osteosarcoma), TP53 and RB1 mutations (Leiomyosarcoma), CDKN2A/B deletions (Undifferentiated Pleomorphic Sarcoma and Chondrosarcoma), and SS18 rearrangements (Synovial Sarcoma). Conclusions: Genomics-guided therapy in sarcoma is feasible and impactful. Expanding timely access to molecular profiling is essential for advancing precision oncology in the MENA region.

Background/Objective: Current treatments for peripheral nerve injury (PNI) lack robust evidence to suggest complete recovery; hence, alternative therapeutics offer new opportunities to develop more effective protocols. Mushroom species and their related components are considered potential candidates for peripheral nerve repair, but their specific effects and underlying mechanisms are not fully understood. This systematic review presents the available evidence on the use of mushroom species for PNI therapy, including the bioactive components and mechanisms of action. Methodology: A comprehensive literature search in three databases (PubMed, Scopus, and Google Scholar) led to the synthesis of 11 records published between 2010 and 2024. Qualitative analysis revealed the neuroregenerative potential of four mushrooms: Amanita muscaria (n = 2), Hericium erinaceus (n = 5), Lignosus rhinocerotis (n = 3), and Flammulina velutipes (n = 1), with aqueous extracts as the most common type of ingredients used (n = 4) relative to specific components such as muscimol, polysaccharide, Erinacine S, and nerve-guided conduits (NGCs). Results: These mushroom-derived treatments enhanced the migration of Schwann cells mainly via the FGF-2 signalling and MAPK pathway. In vivo studies also revealed the ability of H. erinaceus, A. muscaria, and L. rhinocerotis to promote peripheral nerve repair and functional recovery, with evidence suggesting the role of neurotrophic factors, anti-apoptotic signalling, and pro-inflammatory substances. H. erinaceus was identified as the most promising for potential clinical applications, given the stronger evidence-based data and its relatively safer components compared to A. muscuria and other mushroom species. Conclusions: Despite presenting the potential use of mushrooms in managing PNIs, the existing approaches need to be subjected to clinical research to accelerate the development of future therapeutics and preventive measures for PNIs.

Background: Primary fibula tumours are rare, representing approximately 0.25% of all primary bone tumours. While benign lesions are often asymptomatic, malignant ones typically present with pain and functional impairment. Most tumours arise in the proximal third of the fibula, yet the literature regarding their epidemiology and clinicopathological features remains limited. This systematic review aims to synthesise current evidence on presentation, diagnosis, management, and prognosis of primary malignant tumours of the proximal fibula. Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and the Cochrane Register were searched on 28 October 2025 for English-language case reports and case series on primary malignant tumors of the proximal fibula. Two reviewers independently performed study selection and data extraction, collecting information on demographics, tumor characteristics, diagnostic approaches, treatments, and outcomes, with disagreements resolved by a third reviewer. Results: Thirty-three papers involving 228 patients (78 females, 128 males, 22 unknown) were included. The mean age at diagnosis was 22.8 years (range 4-79). The most common symptoms were painful mass and neurological complaints. Osteosarcoma and Ewing's sarcoma were predominant histological types. Limb-sparing surgeries were most common, although 16 patients underwent amputation. At mean follow-up of 48.9 months, local recurrence occurred in 44 cases, and 12 developed distant metastases, most commonly in the lungs. Overall, 38 patients died, 37 due to disease progression. Conclusions: Primary malignant tumours of the proximal fibula, while rare, pose significant therapeutic challenges. Accurate diagnosis, appropriate multimodal treatment, and careful surgical planning are crucial to optimise oncological control and functional outcomes.

Liver fibrosis, the progressive accumulation of scar tissue resulting from chronic liver disease, is increasingly recognized as a multi-system condition, the effects of which extend beyond the liver, affecting brain health. Dementia, characterized by progressively impaired cognition sufficient to impede daily functioning, is a major global health issue with incompletely defined risk factors and pathogenic precursors. To examine the relationship between liver fibrosis and cognitive outcomes, we conducted a comprehensive PubMed literature search, and human studies published in English were included. Evidence is synthesized on the pathophysiology and clinical significance of liver fibrosis, types of dementia, and studies supporting the association between liver fibrosis and cognitive impairment. Meta-analytic data indicate that liver fibrosis is associated with an approximately 30% increased risk of incident dementia (pooled hazard ratio ~1.3), with progressively higher risks across more advanced fibrosis stages. Putative pathomechanisms, potentially modulated by age and sex, include chronic systemic and neuro-inflammation, insulin resistance, vascular dysfunction, and a perturbed intestinal microbiota-liver-brain axis. Non-invasive liver fibrosis diagnostics, advanced neuroimaging, and biomarkers represent key tools for assessing risk. In conclusion, liver fibrosis is a systemic condition that can affect brain health. Early detection, thorough risk assessment and interventions, such as lifestyle changes, metabolic therapies, and antifibrotic treatments, may help protect neural function. Key research gaps are identified, with suggestions for improving understanding of liver fibrosis's connection to dementia or cognitive impairment.

Background/Objectives: Breast cancer is the most common neoplasm among women and remains the leading cause of cancer-related mortality in the female population worldwide. Tumor cells exist within a highly oxidative microenvironment, which promotes the formation of substantial amounts of lipid peroxides. However, the clinical significance of circulating lipid peroxides in breast cancer is still not well understood. Methods: In this study, we quantified systemic lipid peroxide levels in plasma samples from 408 breast cancer patients and examined their associations with key clinicopathological parameters to evaluate their potential as disease biomarkers. Data are reported as relative light units (RLU). Results: Our findings revealed significantly higher lipid peroxide levels in HER2-amplified tumors compared with estrogen-receptor-positive tumors (1,133,494 ± 102,409 RLU vs. 951,883 ± 47,535 RLU; p = 0.0438). Elevated levels were also observed in patients with triple-negative breast cancer relative to those with Luminal A (1,163,323 ± 109,640 RLU vs. 875,633 ± 49,601 RLU; p = 0.0356) and Luminal B tumors (1,163,323 ± 109,640 RLU vs. 1,071,779 ± 98,329 RLU; p = 0.0254). In addition, increased lipid peroxidation was detected in patients with high-grade tumors (G3: 1,141,035 ± 101,045 RLU vs. G1-G2: 949,658 ± 46,119 RLU; p = 0.0346) and in those classified as at high risk of recurrence or death compared with low-risk patients (1,209,530 ± 95,396 RLU vs. 978,318 ± 229,526 RLU; p = 0.0054). Overweight patients also exhibited higher lipid peroxide levels than eutrophic individuals (1,131,233 ± 59,633 RLU vs. 820,772 ± 57,653 RLU; p = 0.0142). Conclusions: Collectively, these results suggest that circulating lipid peroxides may serve as potential biomarkers for recurrence and death risk in breast cancer, particularly among patients with more aggressive tumor phenotypes.

Background/objectives: Osteoporosis is a multifactorial skeletal disorder in which chronic inflammation, dysregulated cytokine signaling, and metabolic imbalance contribute to excessive bone resorption and impaired bone formation. Asiatic acid has demonstrated bone-protective effects, but its molecular mechanisms in osteoporosis remain incompletely understood. This study aimed to investigate the anti-osteoporotic mechanisms of asiatic acid using an integrative in silico strategy.

Methods: Network pharmacology analysis was performed to identify osteoporosis-related molecular targets of asiatic acid. Molecular docking was used to predict the binding modes and affinities between asiatic acid and its target proteins. Molecular dynamics simulation was used to assess the structural stability and interaction persistence of the asiatic acid-protein complex.

Results: Network pharmacology identified 135 overlapping targets between asiatic acid and osteoporosis, with IL-6, STAT3, PPARG, and NFKB1 emerging as key hubs. KEGG analysis indicated the PPAR signaling pathway as a potential mechanism underlying the anti-osteoporotic effect. Molecular docking showed strong binding energies of asiatic acid with all predicted target proteins, with the highest affinity observed for IL-6, involving key residues ASN61, LEU62, GLU172, LYS66, and ARG168. Consistently, molecular dynamics simulation confirmed stable binding of asiatic acid to IL-6, with persistent interactions with ASN61, LYS66, LEU62, LEU64, and GLN154 mediated by hydrogen bonds, water bridges, and hydrophobic interactions.

Conclusions: This integrative in silico study provides mechanistic insight into the potential anti-osteoporotic actions of asiatic acid, implicating IL-6 as a plausible upstream molecular target. These results establish a robust mechanistic framework for future translational studies exploring asiatic acid as a natural therapeutic candidate for osteoporosis.

Background: The prognostic relevance of surgical timing at glioblastoma recurrence remains uncertain, and definitions of early versus delayed reoperation vary widely. Whether earlier surgery provides meaningful survival or functional benefit has not been clearly established. Methods: Databases including PubMed, Embase, Scopus, and Web of Science were searched from inception to May 2025. Eighteen observational studies met the inclusion criteria, fourteen of which provided extractable hazard ratios for survival. The primary outcome was overall survival after reoperation; secondary outcomes included functional status (ΔKPS or discharge home) and major postoperative complications. Random-effects models with Hartung-Knapp adjustment were used, with subgroup analyses stratified by KPS, extent of resection, and eloquence. Results: Across 2267 reoperated patients from 14 survival studies, earlier reoperation was associated with significantly longer survival (pooled HR 0.86; 95% CI 0.78-0.95). Subgroup analyses showed stronger effects in patients with KPS ≥ 70 (HR 0.81; 95% CI 0.72-0.92), non-eloquent tumors (HR 0.84; 95% CI 0.75-0.94), and near-total/gross-total resection (HR 0.79; 95% CI 0.68-0.93). Functional outcomes were pooled from 9 studies (n = 1182), demonstrating higher odds of postoperative stability or improvement with early surgery (OR 1.28; 95% CI 1.12-1.46). Major complications were reported in 9 studies (n = 1344) and did not differ between groups (OR 0.98; 95% CI 0.81-1.19). Sensitivity analyses and influence diagnostics showed consistent effect estimates and no undue single-study influence. Conclusions: Earlier reoperation for recurrent glioblastoma is associated with improved survival and better functional outcomes without increased morbidity in appropriately selected patients. Surgical timing should be incorporated into multidisciplinary planning. Prospective studies with standardized timing definitions and time-dependent modeling are needed to validate these findings.

Background/Objectives: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires continuous glycemic monitoring to prevent acute and long-term complications. In recent years, Diabetic Alert Dogs (DADs) have been increasingly used as an adjunctive strategy to assist individuals with T1DM by alerting glycemic fluctuations through olfactory detection of physiological changes. Despite growing interest, the available evidence remains heterogeneous and fragmented. Methods: Therefore, this scoping review was conducted to address the following research question: "What evidence is available regarding the relationship between Diabetic Alert Dogs (DADs) and glycemic monitoring in individuals with T1DM?", conducted in accordance with the Joanna Briggs Institute methodology and reported following the PRISMA Extension for Scoping Reviews. Results: Searches were performed in PubMed, Scopus, and Web of Science without time restrictions. After duplicate removal (n = 485), 2379 records were screened, of which 24 articles underwent full-text assessment and 10 studies met the predefined inclusion criteria. Regarding glycemic alteration detection, most studies (7/10) reported that DADs could identify both hypoglycemic and hyperglycemic episodes, while the remaining studies focused exclusively on hypoglycemia detection. Sensitivity values were consistently higher for hypoglycemia than for hyperglycemia, and none reported false alert rates exceeding 20%. In addition to glycemic alert performance, improvements in perceived safety, independence, and quality of life were described in half of the included studies (5/10). Conclusions: By systematically mapping the characteristics, outcomes, and methodological approaches of studies involving DADs, this scoping review provides an overview of current evidence and identifies key knowledge gaps in training protocols, outcome standardization, and performance reporting.

The major subtypes of leukemia show sex differences. This review summarizes current knowledge and identifies gaps regarding sex differences across acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphoblastic leukemia in epidemiology, mortality and survival rates, risk factors, and epigenetic, metabolomic, and sex-specific patterns. Males have higher incidence and mortality rates of leukemia compared to females, emphasizing the importance of biological sex. Underreporting of sex differences in leukemia is highlighted, suggesting that sex is often overlooked as a research variable. A significant clinical observation is that women demonstrate higher overall survival rates but experience more severe treatment-related toxicity. Clinically, women tend to survive longer but experience more severe side effects. In contrast, a significant clinical observation in pediatric leukemia contradicts this enigma, suggesting that sex differences may be less pronounced during childhood. These differences play a significant role in how the disease develops. This review presents a sex-based perspective for hematological and biochemical patterns, genetic risk factors, environmental, lifestyle, and parental risk factors, epigenetics and metabolites. Furthermore, males and females might have different responses to the same toxic, environmental, and hormonal exposures. Trying to understand these disparities better based on molecular mechanisms is considered an approach for precision medicine.