Background/AimLactose intolerance (LI) is a common clinical condition associated with reduced lactase enzyme activity. The oral lactose tolerance test (OLTT), although widely used for diagnosis, has several limitations such as fasting, multiple blood collections, and gastrointestinal discomfort. As an alternative, genetic testing targeting the −13910C>T polymorphism in the MCM6 gene, a regulator of lactase expression, has gained prominence as it is non-invasive, rapid, and unaffected by physiological variation. This study aimed to evaluate the frequency of the −13910C>T polymorphism of the MCM6 gene in the population of Fortaleza and compare the genotyping results with the OLTT, to verify its diagnostic applicability.Materials and MethodsA descriptive study was conducted with data from 2359 patients examined between January 2022 and May 2025 at a private laboratory. Concordance between genotyping and OLTT was analyzed in 24 patients who underwent both tests, with OLTT considered the reference standard. Sensitivity, specificity, accuracy, and Kappa coefficient were calculated. All analyses were performed using R software.ResultsThe median age of participants was 7 years (range=0.06-100 years). The observed genotype frequencies were 52.90% for the CC genotype, 38.74% for CT, and 8.35% for TT. The Kappa test demonstrated moderate agreement between the genetic test and OLTT [k=0.583 (p=0.00413)], with a sensitivity of 81.82% [95% confidence interval (CI)=48.22-97.71], overall accuracy of 79.17%, and specificity of 76.92% (95%CI=48.16-94.96).ConclusionGenotyping for the −13910C>T polymorphism in the MCM6 gene represents a promising diagnostic alternative for lactose intolerance, offering a feasible and less invasive approach with good sensitivity and specificity.

Background/AimPulmonary arterial hypertension (PAH) is a significant and challenging complication for patients with systemic lupus erythematosus (SLE). It is thought to arise from immune dysregulation and vascular remodeling, ultimately leading to progressive right heart failure. Molecular hydrogen therapy, a selective antioxidant and anti-inflammatory agent, may modulate the immune responses seen in autoimmune diseases. This case report details the use of adjuvant hydrogen capsule therapy in a patient with SLE with PAH, suggesting its potential as a novel approach for this difficult clinical condition.Case ReportA 42-year-old Taiwanese woman with SLE-PAH received hydrogen capsule therapy, during which serial immunophenotyping revealed dynamic changes in suppressive markers including programmed cell death protein 1 (PD1) and Fas cell surface death receptor (FAS), as well as regulatory T- and B-cell subsets. Notably, the populations of double negative and class-switched memory B-cells decreased during therapy, suggesting durable immune suppression. These results support the effect of hydrogen capsule therapy in achieving immune tolerance and inflammation modulation.ConclusionThis case study suggests that molecular hydrogen therapy may be a promising treatment for patients with SLE-PAH, particularly due to its immunomodulatory effects.

Background/AimPreoperative planning in oncoplastic and reconstructive breast surgery requires synthesizing patient- and tumor-specific variables with aesthetic considerations. Variability in documentation and expertise may hinder reproducibility across centers. Large language models (LLMs) can process structured data into consistent outputs. We assessed whether a prompt-engineered artificial intelligence (AI) assistant (BREAST AI-PLAN) could replicate multidisciplinary team (MDT) decisions and aesthetic scores from routinely collected clinical data.Patients and MethodsThis single-center retrospective study included 30 women undergoing breast cancer surgery. Each case was recorded in a standardized form covering demographics, comorbidities, breast anatomy, tumor biology, and staging. This form was used to generate structured prompts for the AI assistant. The AI returned eight outputs: 1) neoadjuvant therapy suitability; 2) planned surgery; 3) surgical approach; 4) reconstruction type; 5) direct-to-implant feasibility; 6) implant type; 7) adjuvant therapy; and 8) an aesthetic score (BCCT.core-aligned). Clinical MDT decisions were the reference standard. Agreement was measured using Cohen’s κ, with linear and quadratic weights for aesthetics.ResultsMean age was 59.2±9.8 years; median body mass index (BMI) 24.2 (20.9-26.8). One patient carried a BRCA2 mutation; 13.3% had prior radiotherapy; 33.3% were smokers. Tumors were mainly Luminal A (43.3%) and Luminal B (26.7%). Agreement was very good for neoadjuvant therapy (κ=0.91; observed 96.7%) and good/moderate for planned surgery (κ=0.58; observed 70.0%), surgical approach (κ=0.43; observed 60.0%), reconstruction (κ=0.36; observed 57.1%), and adjuvant therapy (κ=0.29; observed 64.3%). Aesthetic scoring showed high observed concordance (0.778-0.896) but only slight weighted κ (0.14-0.16).ConclusionBREAST AI-PLAN reproduced MDT planning elements and aesthetic assessments with moderate-to-very-good agreement. Transparent, auditable AI assistance may standardize surgical planning and support training. Prospective validation with imaging integration is warranted.

Background/AimPositron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) is frequently used to differentiate schwannomas from malignant peripheral nerve sheath tumors. Schwannomas exhibit pathological heterogeneity, with highly cellular (Antoni A) and hypocellular (Antoni B) areas, but current PET/CT methods do not adequately reflect this heterogeneity. This study aimed to compare imaging characteristics of schwannomas in the trunk versus the extremities, with emphasis on metabolic heterogeneity.Patients and MethodsThis retrospective study included patients with solitary schwannomas who underwent MRI and 18F-FDG PET/CT before surgical excision (June 2013-September 2023). Exclusion criteria were plexiform, multiple, biopsy-only lesions, and tumors originating from internal organs. Tumors were classified as trunk or extremity lesions. MRI was used to determine size and volume, while PET/CT measured SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Heterogeneity was assessed using three indices: MTV-to-volume ratio (MTV/volume), SUV-based heterogeneity index (HISUV), and metabolic region-adjusted SUV-based heterogeneity index (MRA-HISUV).ResultsFifty-six patients were included. Trunk schwannomas were larger than extremity tumors in diameter (4.33 cm vs. 2.77 cm; p<0.05) and volume (27.71 cm3vs. 6.25 cm3; p<0.05). SUVmax (4.09 vs. 3.71) and SUVmean (2.47 vs. 2.22) did not differ significantly. MTV (18.43 cm3vs. 6.19 cm3, p<0.05) and TLG (58.41 vs. 14.40, p<0.05) were higher in trunk tumors. MTV/volume ratio was lower (0.77 vs. 1.12, p<0.05), while HISUV and MRA-HISUV were higher in trunk schwannomas (1.79 vs. 1.65 and 2.36 vs. 1.49, p<0.05).ConclusionTrunk schwannomas were larger and exhibited higher metabolic activity and heterogeneity. Novel parameters such as MTV/volume and MRA-HISUV may enhance the characterization of schwannoma heterogeneity.

Background/AimSinonasal papilloma is a histologically benign tumor that demonstrates locally aggressive behavior, with a propensity for recurrence and potential for malignant transformation. This study aimed to evaluate the clinical characteristics, recurrence patterns, and malignant transformation of sinonasal papillomas and to propose appropriate follow-up strategies.Patients and MethodsA retrospective analysis was conducted on 83 patients diagnosed with sinonasal papilloma at our institution. Clinical features, surgical treatments, recurrence intervals, and oncologic outcomes were analyzed. Tumors were staged using the Krouse classification for benign cases and UICC TNM staging for carcinoma-associated with papilloma cases.ResultsAmong 83 patients (62 men, 21 women; median age 68), 74 (89.2%) were diagnosed as benign papillomas and nine (10.8%) as carcinoma-associated with papilloma. The recurrence rate among benign cases was 14.9% (11/74), with a median time to recurrence of 5 years and two months. Recurrence intervals exhibited a trimodal distribution: within two years (36.4%), between 2-10 years (36.4%), and after 10 years (27.3%). Malignant transformation occurred in one case (1.2%), and eight additional cases were found to be associated with carcinoma. Five of these were initially misdiagnosed as benign, underscoring the diagnostic limitations of imaging modalities. Krouse T3/T4 lesions were more frequently associated with recurrence and malignancy. Approximately 48.6% of patients discontinued follow-up, often before reaching the threshold for late recurrence.ConclusionSinonasal papillomas require long-term surveillance beyond five years due to their potential for late recurrence and malignant transformation. Preoperative suspicion of malignancy remains challenging, particularly in Krouse T3 lesions. Clinicians should consider extended follow-up, especially in patients with advanced tumor stage, and adopt a tailored surgical strategy to achieve complete resection. Patient education regarding recurrence risk is essential for optimizing long-term outcomes.

Background/AimThe epidermal growth factor receptor (EGFR) is a key driver in bladder cancer progression. This study investigated the tumor-suppressive role of miR-124-3p and its regulatory effect on EGFR.Materials and MethodsTSGH8301 and T24 bladder cancer cells were treated with the EGFR inhibitor erlotinib or transfected with an miR-124-3p mimic. Cell viability, proliferation, migration, and invasion were assessed using MTT, colony formation, and transwell assays. EGFR targeting was confirmed via Western blot, immunofluorescence, and luciferase reporter assays.ResultsErlotinib and miR-124-3p both reduced cell viability and proliferation. miR-124-3p significantly inhibited EGFR phosphorylation and expression, suppressed migration and invasion, and downregulated the EGFR downstream targets MMP2, MMP9, and VEGF-A. Luciferase assays confirmed the direct binding of miR-124-3p to EGFR 3’UTR.ConclusionmiR-124-3p suppresses bladder cancer cells progression by directly targeting and inactivating EGFR, thereby impairing cell proliferation, migration, and invasion. These findings highlight miR-124-3p as a potential therapeutic agent in EGFR-driven bladder cancer.

Background/AimThis study investigated the prognostic impact of human epidermal growth factor-2 receptor (HER2) status on the survival of patients with metastatic triple-negative breast cancer (TNBC).Patients and MethodsThis multicenter, retrospective study included 168 patients diagnosed with recurrent or de novo metastatic TNBC between April 2013 and September 2024. Patients were categorized into two groups: HER2-negative (n=121, 72%) and HER2-low (n=47, 28%). Clinicopathological features and survival outcomes were compared between groups.ResultsThe median follow-up was 44 months [95% confidence interval (CI)=35.7-52.2]. All patients received systemic chemotherapy as part of their first-line treatment. The median progression-free survival (PFS) in all patients was 9 months (95%CI=7.7-10.3 months). The median overall survival (OS) in all patients was 22 months (95%CI=17.4-26.5 months). Higher Ki67 value at diagnosis was a significant poor prognostic factor for median OS (29 months vs. 15 months, p<0.001). HER2-negative patients had significantly worse median OS than HER2-low patients (19 months vs. 33 months, p=0.026). In multivariate analysis, the HER2-low group had significantly longer median OS than the HER2-negative group [hazard ratio=0.64 (95%CI=0.42-0.98), p=0.040].ConclusionHER2-low expression was associated with significantly improved survival compared with HER2-negative status in metastatic TNBC. These findings highlight HER2 status as a potential prognostic factor, particularly relevant in settings with limited access to novel therapies such as immunotherapy or antibody-drug conjugates.

Background/AimZinc finger CCCH-type containing 12A (ZC3H12A), also known as monocyte chemotactic protein-induced protein 1, has emerged as having a potential role in the landscape of some human cancer types, contributing to anti-tumorigenesis through signaling pathways of inflammation, apoptosis, autophagy and angiogenesis. However, its specific impact on the prognosis of oral squamous cell carcinoma (OSCC) remains to be investigated.Patients and MethodsWe conducted in-vitro cell models in a pilot study and performed a retrospective cohort study involving 242 patients with OSCC to unravel the association between ZC3H12A expression level and oral cancer prognosis during 3, 5, and 10-year follow-up.ResultsThe findings showed that endogenous ZC3H12A expression was decreased in both the malignant (BQO) and highly metastatic (HSC-3-M3) OSCC cell lines compared to dysplastic oral keratinocytes (DOK) and the parental cell line of HSC-3-M3 (HSC-3). The analysis of clinical cancerous tissue arrays from patients with OSCC showed a significant association between complete loss of ZC3H12A expression and heightened cancer mortality, particularly at 3 and 5 years. Moreover, the complete loss of ZC3H12A expression may be associated with increased risk of lymph node involvement in OSCC.ConclusionOur investigation suggests that the complete loss of ZC3H12A expression exacerbated the unfavorable prognosis of OSCC in this Taiwanese population, but further study on elucidating the gradual decline of ZC3H12A expression in OSCC is imperative.

Background/AimType 2 diabetes mellitus (T2DM) is a prevalent disorder characterized by an increased concentration of blood glucose and impaired insulin function. Throughout the course of the disease, β-cell function fails and insulin production decreases. Studying the molecular systems responsible for insulin production, release, and action is crucial for the management and treatment of the disease. Thus, this study aimed to scrutinize the therapeutic efficacies of oxytocin (OXT) on nicotinamide (NA)/streptozotocin (STZ)-induced diabetes in rats and elucidate the underlying mechanisms.Materials and MethodsWistar rats were supplied a single intraperitoneal (i.p.) dose of NA (120 mg/kg) 15 min before an i.p. injection of STZ (60 mg/kg) after fasting for 16 h. Ten days later, the diabetic rats were orally administered OXT every day for eight weeks at dose levels 0.5, 1, and 2 IU/kg.ResultsThe treatment of diabetic rats with OXT significantly improved oral glucose tolerance, serum insulin and C-peptide concentrations, and pancreatic islets’ structure and function. Furthermore, the activities of liver glucose-6-phospatase and glycogen phosphorylase significantly decreased. OXT treatment also resulted in an increase in serum adiponectin levels, while the levels of serum resistin, omentin, vaspin, and free fatty acids significantly decreased. Additionally, OXT significantly alleviated the mRNA levels of components of the PI3K-AKT and AMPK signaling pathways as well as their effectors including PPARγ, insulin receptor (IR), IR substrates 1 and 2 (IRS1 & IRS2), PI3K, AKT, AMPK, and glucose transporter 4 (GLUT4) in visceral adipose tissues of diabetic rats.ConclusionOXT can exert antidiabetic effects and may be useful for developing multiple targeted therapeutic strategies for diabetes treatment. The effects may be mediated via improvement in β-cell function, insulin secretory response, and insulin sensitivity.

Background/AimDrug metabolism and thus drug efficacy can be affected by individual differences in cytochrome P450 2D6 enzyme (CYP2D6) due to genetic polymorphism in its gene. In this study, we aimed to investigate CYP2D6 allelic variants in drug metabolism among patients with COVID-19 with comorbidities.Patients and MethodsThis prospective case-control study, approved by the Pamukkale University Ethics Committee, investigated CYP2D6 polymorphisms (*4, *5, *7, *10) and COVID-19 outcomes in the Emergency Department between April and June 2020. Genomic DNA was extracted from whole blood, and genotyping was performed by polymerase chain reaction followed by sequencing on the ABI PRISM 7700 platform. Statistical analyses, including Student's t-test, Mann-Whitney U-test, chi-square test, and Fisher's exact test, were performed for laboratory and clinical data comparing between wild-type and heterozygous variants, and significance was determined as p<0.05. Data visualization was performed using SankeyMATIC, STATA 16.1 SE, and GraphPad Prism 5.0.ResultsAmong the 99 patients, 71 were identified as having one or more comorbid conditions. Comorbidity analysis showed that the absence of comorbidities was most common in CYP2D6*4 (38.46%), *5 (40%), and *7 (29.63%) heterozygotes, while hypertension and diabetes were also common. CYP2D6*10 heterozygotes (n=3) presented with cardiovascular diseases, osteomalacia, and arrhythmia. In particular, CYP2D6*5 heterozygotes had significantly lower lymphocyte counts. A trend toward differences was observed for hemoglobin in CYP2D6*4 and platelet count for CYP2D6*5 and CYP2D6*10, but these were not statistically significant.ConclusionThis study highlights the diverse clinical profiles of COVID-19 patients with different CYP2D*6 variants, particularly the association between CYP2D6*5 heterozygosity and a reduced lymphocyte count.