Despite their profound influence on the lives of individuals with schizophrenia, few studies explore delusions and hallucinations from the first-person perspective using a phenomenological approach. This study aimed to examine how individuals diagnosed with schizophrenia experience delusions and hallucinations from their own perspective.

This descriptive phenomenological study was conducted between August and September 2023. Semi-structured, in-depth interviews were conducted with 14 individuals diagnosed with schizophrenia who regularly attended a state community mental health center in eastern Turkey. Interviews were audio-recorded, transcribed verbatim, and analyzed using Colaizzi's seven-step method. The study was reported in line with the COREQ checklist.

Four main themes were identified: (1) effects of schizophrenia, (2) triggers for delusions and hallucinations, (3) the impact of delusions and hallucinations on daily life, and (4) coping with delusions and hallucinations. Ten sub-themes captured psychological, physical, and social effects and triggers, as well as control mechanisms, challenges in life, perceived social support, and emotions.

The findings highlight the pervasive psychological, physical, and social burden of living with delusions and hallucinations and the variability in coping resources and support. Developing and evaluating tailored psychosocial interventions may help individuals with schizophrenia manage these experiences more effectively. These findings suggest the need for developing psychoeducation programs focused on identifying personal symptom triggers, family-based support interventions that enhance communication and stigma reduction, and community mental health interventions aimed at strengthening coping skills, social participation, and emotional regulation.

SUL-138 is an orally bioavailable 6-chromanol which is in development as therapeutic against Noncommunicable Chronic Diseases (NCDs) including Chronic Heart Failure, Chronic Kidney Disease, Alzheimer's and Parkinson's Disease. The compound improves mitochondrial function by preserving respiration through activation of complex I and IV during disease. Thorough comprehension of preclinical Absorption, Distribution, Metabolism and Excretion (ADME) is pivotal for the safety assessment prior to starting Phase I clinical trials. To this end, a single oral or intravenous dose of [¹⁴C]-SUL-138 at a therapeutic and near Maximum Tolerated Dose (MTD) dose level were administered to rats and minipigs for characterization of ADME properties. Non-radiolabelled SUL-138 and radiolabelled [¹⁴C]-SUL-138 were administered as single oral or intravenous dose to intact and bile duct-canulated rats and to minipigs to investigate pharmacokinetics of total radioactivity and SUL-138, tissue distribution by Quantitative Whole-Body Autoradiography (QWBA), excretion and metabolite profiling. The pharmacokinetic profiles of [¹⁴C]-SUL-138 and SUL-138 indicated rapid absorption, tissue distribution and extensive metabolism in both species. In rats, the QWBA showed that drug-related radioactivity was widely distributed throughout nearly all tissues shortly after dosing. Total radioactivity was completely eliminated; in rats excretion was mainly via the faecal route, whereas in minipigs elimination was equal between the faecal and renal excretory routes. Primary metabolic pathways for clearance of SUL-138 were oxidation, N-dealkylation and glucuronidation. Plasma exposure to the parent was low compared to the main circulating oxidation metabolite M2 and glucuronide conjugate M7 in rats and glucuronide conjugates M7 and M8 in minipigs. In conclusion, ADME properties of SUL-138 are characterized by rapid absorption, wide tissue distribution, extensive metabolism and excretion via the renal and faecal route. Oxidation and glucuronidation are the main metabolic pathways in both nonclinical safety species.

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in non-small cell lung cancer (NSCLC) and has been clinically associated with improved responses to programmed cell death protein-1 (PD-1) blockade. Whether this enhancement is directly attributable to COPD and the mechanisms driving it remains unclear.

We conducted an integrated translational study combining three clinical cohorts with multi-omics profiling, including single-cell RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence. Fresh surgical tumor specimens were subsequently used to perform in vitro functional assays to validate epithelial-immune interactions identified through multi-omics analyses.

COPD induces epithelial remodeling that expands a distinct basal-like tumor cell population with progenitor-like features in NSCLC. These cells activate a dominant CXCL14-CXCR4 signaling axis to preferentially recruit macrophages producing CXCL9, thereby establishing a localized microenvironment that is more permissive for cytotoxic T cell infiltration. This spatially restricted tumor-macrophage recruitment circuit was functionally validated and found to be enriched in patients with NSCLC who achieved a major pathological response following neoadjuvant anti-PD-1 therapy.

Our findings define a mechanistic link between COPD comorbidity and enhanced PD-1 blockade efficacy. The presence of this tumor-macrophage axis in patients with NSCLC with favorable immunotherapy outcomes highlights its translational potential as both a predictive biomarker and a therapeutic target to improve checkpoint blockade responsiveness.

This work was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0529403) and the National Natural Science Foundation of China (82370028, 82422001, 32330061, and 82303972).

Osmotic nephropathy is an infrequent drug‑induced complication characterized by vacuolization of renal tubular cells secondary to lysosomal uptake, which increases osmotic pressure within the proximal tubule. This lesion pattern has been linked to administration of intravenous immunoglobulins, iodinated contrast agents, mannitol, dextrans and glucose solutions, and more recently to the use of sodium-glucose cotransporter‑2 (SGLT2) inhibitors.

A 49‑year‑old man with a history of hypertension, type 2 diabetes mellitus and obesity, chronically treated with empagliflozin, presented with diarrhea, abdominal pain and oliguria. Laboratory tests revealed acute kidney injury with a serum creatinine of 13 mg/dL and electrolyte disturbances. In light of a suspected rapidly progressive glomerulonephritis, renal replacement therapy was initiated owing to failure of hydration. Renal biopsy showed diffuse tubular vacuolization compatible with osmotic nephropathy, leading to discontinuation of the SGLT2 inhibitor. The patient's renal function recovered after two weeks of hemodialysis.

Osmotic nephropathy is a rare histopathological diagnosis associated with exposure to hyperosmolar agents, as exemplified by this case related to empagliflozin use. The proposed pathophysiological mechanism involves lysosomal uptake secondary to increased intratubular osmotic pressure caused by glucosuria. Predisposing factors include therapy with SGLT2 inhibitors, diabetes mellitus, advanced age and pre-existing mild chronic kidney impairment. The cornerstone of management is discontinuation of the offending agent and supportive measures. It is recommended that SGLT2 inhibitors be withheld during episodes of diarrhea or acute dehydration to prevent further renal impairment.

Type 2 diabetes mellitus (T2DM), a chronic hyperglycemic disorder, adversely affects multiple organs, including the kidneys, retina, and cardiovascular system. Despite significant advancements, the understanding of early screening, diagnosis, prognosis, biomarkers, and the molecular pathways involved in T2DM and its complications remains limited. Metabolomics has emerged as a powerful tool for exploring complex metabolic networks, allowing rapid investigation of disease-specific metabolic processes and offering deeper insights into pathophysiological mechanisms. This review evaluates the application of metabolomics in T2DM research, with a particular emphasis on its role in risk prediction and elucidating disease mechanisms. By summarising current literature, the review highlights metabolomics' contributions to the discovery of T2DM biomarkers, the understanding of metabolic mechanisms, and the study of T2DM complications. Additionally, it examines its potential in personalised diagnosis, prognosis, and treatment. Metabolomics plays a pivotal role in T2DM research, as the analysis of metabolites in biological fluids facilitates the identification of biomarkers for early diagnosis and risk prediction, provides insights into disease mechanisms, supports precision medicine, and enables early detection of diabetic complications. However, challenges remain, and future efforts should focus on multi-omics cohort studies to advance its clinical applications.

To present a new nomogram that uses preoperative clinical features to predict benign pathology in clinical T1a solid renal masses.

Demographic, clinical and pathologic data related to 579 patients diagnosed with clinical solid T1a renal mass were retrospectively collected. Univariate and multivariable logistic regression analyses were used to determine the variables related to benign pathology. Variables with statistical significance were used to develop a nomogram.

The female-to-male ratio was 240/339, with a median age of 56 (47-64) years. 40% (232/579) of all patients had a diagnosis of hypertension or diabetes mellitus or both. All patients had solitary renal lesion with a median size of 3.0 (23-35) cm. Cystic component was noticed in 20.7% (119/579) of the lesions. Benign pathology was detected in 19.9% (115/579) of cases. On univariate analysis, female gender, age less than 60 years, absence of hypertension or diabetes mellitus, symptomatic presentation, smaller tumor size and absence of cystic component were all related to benign pathology. Female gender, age less than 60 years, smaller tumor size and absence of cystic component kept their significance on multivariable analysis. A nomogram was built depending on these variables. The model was close to the ideal and had a c-index value of 0.79.

The nomogram in the present study has good predictive ability for benign pathology in T1a solid renal masses. This will help physicians and patients while making decisions related to the management paradigm.

Systemic inflammatory and prognostic indices are emerging biomarkers in bladder cancer. Diabetes mellitus (DM), a chronic inflammatory disease, and Bacillus Calmette-Guérin (BCG) therapy may influence these indices in non-muscle invasive bladder cancer (NMIBC).

To evaluate the impact of DM and BCG therapy on inflammatory and prognostic indices in patients with NMIBC.

A retrospective study of 156 NMIBC patients was conducted. Patients were stratified by DM and BCG status (DM+/DM-; BCG+/BCG-), and into four subgroups (DM-/BCG-, DM+/BCG+, DM-/BCG+, DM+/BCG-). Laboratory and clinical parameters were compared using standard statistical tests (t-test, Chi-square, ANOVA). A p-value <0.05 was considered significant.

DM+ patients had significantly higher glucose (p = 0.001), HbA1c (p = 0.017), GKR (p = 0.014), and lower PNI (p = 0.014). Tumor recurrence was more common in DM+ (p = 0.021). In the BCG comparison, albumin (p = 0.002) and PNI (p = 0.009) differed. Four-group analysis showed significant differences in tumor grade, tumor recurrence, HbA1c, albumin, PNI, and MPR (all p < 0.05), especially between DM+/BCG+ and DM-/BCG+.

DM and BCG therapy are associated with systemic inflammatory and prognostic indices in NMIBC. GKR and PNI may serve as practical, cost-effective markers for recurrence risk stratification.

Diabetic liver injury (DLI), a common complication of diabetes mellitus, is characterized by metabolic disturbances that induce hepatic dysfunction and histopathological alterations such as steatosis, inflammation, and fibrosis. These alterations may progress to cirrhosis with limited effective therapies. Total flavones from Abelmoschus manihot (L.) Medik. [Malvaceae] extract (TFA), a traditional bioactive compound, has attracted attention due to its potent anti-inflammatory and metabolic regulatory properties. However, the capacity of TFA to ameliorate DLI and its underlying mechanism remain unknown.

This study aimed to investigate the hepatoprotective effects of TFA against DLI and to elucidate its underlying mechanism, with a particular focus on its association with the regulation of the PI3K/AKT/Nrf2 signaling pathway and ferroptosis.

Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was employed to identify TFA metabolites. DLI mouse model was established by high-fat diet (HFD) feeding and streptozotocin (STZ) injection. The mice were randomly allocated into four groups (n = 8): Control, Model, TFA-L, and TFA-H. TFA was administered daily by oral gavage for 12 consecutive weeks. In vitro hepatocyte model was induced with high glucose (HG) and oleic acid/palmitic acid (OA/PA). To systematically clarify the pharmacodynamic basis and molecular mechanisms underlying which TFA ameliorates DLI via inhibiting ferroptosis through the PI3K/AKT/Nrf2 pathway, integrated multi-omics strategies including network pharmacology, transcriptomics, and metabolomics were coupled with molecular docking, cellular thermal shift assay (CETSA), and experimental validations-including reactive oxygen species (ROS) detection, superoxide dismutase (SOD), glutathione (GSH), and oxidized glutathione (GSSG) determination, ferric/ferrous ion assay, and lipid peroxidation detection.

A total of 56 metabolites in TFA were identified using UHPLC-Q-Orbitrap HRMS. TFA significantly ameliorated metabolic disorders in HFD/STZ-induced DLI mice, as evidenced by reduced body weight, improved glycemic control, attenuated dyslipidemia, and decreased hepatic steatosis and injury markers (p< 0.05). Concomitantly, histopathological and immunohistochemical analyses revealed substantial alleviation of liver damage and fibrosis. Furthermore, integrated network pharmacology, transcriptomics, and metabolomics suggested that TFA exerts multi-target effects, potentially involving the PI3K/AKT/Nrf2 pathway-an axis that regulates amino acid and lipid metabolism, while also suppressing ferroptosis-related molecular programs to mitigate metabolic and hepatic disturbances. In line with this, molecular docking and CETSA suggested potential binding interactions between key TFA components and core targets of the PI3K/AKT/Nrf2 pathway as well as ferroptosis regulators. Notably, both in vivo and in vitro experiments consistently demonstrated that TFA alleviates oxidative stress, inflammation, and critically, ferroptosis in hepatic cells-manifested by reduced lipid peroxidation, restored GSH homeostasis, and balanced iron metabolism (p< 0.05). Importantly, these protective effects were abrogated by the PI3K inhibitor LY294002, ferroptosis inducer Erastin, and si-Nrf2, thereby confirming that TFA suppresses ferroptosis via a mechanism dependent on PI3K/AKT/Nrf2 pathway to exert its hepatoprotective effects against DLI (p< 0.05).

TFA exerts hepatoprotective effects against DLI through multi-target regulation, primarily involving the PI3K/AKT/Nrf2 pathway to suppress ferroptosis while concurrently ameliorating metabolic dysfunction, oxidative stress, and inflammation. These findings not only elucidate a novel mechanism of action but also position TFA as a promising therapeutic candidate worthy of further development for the clinical management of DLI.

In this study, we compared symptoms, comorbidities, and healthcare burden between childhood-onset asthma (< 18 years) and early adult-onset (18-39 years) and late adult-onset asthma (≥ 40 years). Among 3546 participants with data on physician-diagnosed asthma and onset age, 46.4% were defined as adult-onset [864 (24.4%) had early adult-onset asthma (18-39 years) and 782 (22.1%) had late adult-onset asthma (≥ 40 years)], which, compared to childhood-onset asthma, presented with more complex, multi-symptom profiles, including productive cough, sputum production, but less wheezing. Allergy-related comorbidities were more common in childhood-diagnosed asthma, while chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, obesity, and chronic sinusitis were more common in adult-onset asthma. Adult-onset asthma also had a higher disease burden, with more frequent medication use and exacerbations. Adult-onset asthma has an underlying complexity, contributing to a vicious cycle of worsening symptoms, increased medication use, and more comorbidities.