Diabetic pulmonary fibrosis(DPF) is a pulmonary complication of diabetes mellitus with complex pathogenesis, and effective treatments are urgently needed. Buyang Huanwu Decoction(BHD), a potential therapeutic agent for DPF, exhibits hypoglycemic, hypolipidemic, anti-fibrotic, and antioxidative stress effects. In this study, DPF rats were administered BHD via gavage for 3 weeks, and changes in body weight, random blood glucose from tail veins, lipid profiles, oxidative stress markers, and pulmonary collagen deposition were observed. Network pharmacology was employed to analyze the targets and mechanisms of BHD in regulating oxidative stress and lipid metabolism to intervene in DPF. Molecular docking and molecular dynamics simulations were conducted to assess the binding affinity of BHD's active components to core DPF targets, and Western blot was used to detect BHD's regulatory effects on key proteins in DPF rat lungs. The results showed that BHD reduced random blood glucose in DPF rats and alleviated hyperglycemia-induced weight loss, with the moderate-dose group exhibiting the most significant effects, comparable to the metformin group. BHD significantly decreased fasting serum levels of low-density lipoprotein cholesterol, triglycerides, and total cholesterol, enhanced the expression of antioxidative enzymes glutathione peroxidase and superoxide dismutase, and suppressed the oxidative end-product malondialdehyde. HE and Masson staining revealed that BHD intervention restored lung structure, reduced foam cell accumulation, and attenuated collagen deposition. Network pharmacology analysis identified mitogen-activated protein kinase 3(MAPK3), vascular endothelial growth factor A(VEGFA), and prostaglandin-endoperoxide synthase 2(PTGS2) as the primary targets of BHD in modulating oxidative stress and lipid metabolism to intervene in DPF. Enrichment analysis indicated that the advanced glycation end products/receptor for advanced glycation end products(AGE/RAGE) pathway in diabetic complications was the core pathway for BHD's intervention in DPF. Molecular docking demonstrated that astragaloside Ⅳ and baicalein exhibited the strongest binding to PTGS2, while 6-hydroxykaempferol and formononetin showed the strongest binding to MAPK3; molecular dynamics simulations confirmed the stability of these four compound systems. Western blot results indicated that BHD significantly inhibited the activation of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2) and reduced RAGE expression in DPF rat lungs. These findings suggest that BHD may exert anti-DPF effects by inhibiting RAGE, thereby influencing downstream ERK1/2 pathway activation, mitigating oxidative stress, lowering lipid levels, and reducing blood glucose.

In this study, a niosomal formulation of vanillic acid was successfully developed to enhance its poor aqueous solubility and antioxidant therapeutic potential. Niosomes were prepared using Span 60 and cholesterol via thin-film hydration method followed by probe sonication and were optimized using a Box-Behnken design. The optimized formulation exhibited a vesicle size of 129.91 ± 2.78 nm, a polydispersity index (PDI) of 0.152 ± 0.06, a zeta potential of - 8.698 ± 0.52 mV, and an entrapment efficiency (EE%) of 35.893 ± 3.45%. Physicochemical analyses confirmed spherical morphology and amorphous drug dispersion. In vitro drug release showed a sustained profile governed by the Korsmeyer-Peppas model, indicating diffusion-controlled release as the main mechanism. Antioxidant assays, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), revealed significantly elevated enzymatic activity in the nanoformulation-treated groups. In vivo evaluation using a diabetic Wistar rat model showed that the 1% Niosome-Vanillic Acid containing formulation led to superior wound closure, increased hydroxyproline content, and improved histopathological features. These findings highlighted nano-encapsulated vanillic acid as a promising therapeutic strategy for diabetic wound healing.

Autophagy is a conserved degradation process in eukaryotic cells that is regulated by autophagy-related genes. During autophagy, lysosomes break down cytoplasmic proteins and damaged organelles. This process plays a pivotal role in cell growth and development, protection against metabolic stress and oxidative damage, and the maintenance of cellular homeostasis through the recycling of cellular components. Pregnancy encompasses crucial events such as decidualization, embryo implantation, and fetal growth. Abnormal autophagy has been implicated in several pregnancy complications and can significantly impact both maternal and fetal health. Understanding the relationship between autophagy and complicated pregnancies could open new avenues for potential therapeutic interventions to improve maternal and fetal outcomes. In this review, we summarize the intricate relationship between autophagy and pregnancy complications, elucidate the role of autophagy in gestation, and discuss the clinical significance of autophagy in mitigating or preventing pregnancy-related disorders.

Type 2 diabetes mellitus (T2DM) and hypertension are prevalent global health concerns associated with increased morbidity, mortality and healthcare expenditure. This study evaluated the effectiveness of patient-centred care (PCC) and population health management (PHM) strategies in improving clinical outcomes and medication adherence among patients with co-existing T2DM and hypertension in Hounslow, UK.

Quantitative intervention study.

A total of 221 patients were selected from 6000 attendees at West Middlesex University Hospital's pre-assessment clinic. Participants were allocated into three groups. Study 1 was a randomised controlled pilot trial with 40 patients assigned to either a PCC intervention group (n=20) or a usual care group (n=20) over 6 months. Study 2 involved 41 patients receiving a pharmacist/nurse-led collaborative PCC intervention for 6 months. Study 3 included 140 patients enrolled in a 6-month community-based PHM lifestyle programme integrated with PCC. Data collection involved patient questionnaires and hospital records, focusing on clinical and behavioural outcomes.

In study 1, the PCC group showed a significant reduction in glycated haemoglobin (HbA1c) (mean decrease 23.2 mmol/mol, 95% CI 4.3 to 42.1) and improved medication adherence compared with controls. The number needed to treat (NNT) was 1.8 (95% CI 1.3 to 7.6). Study 2 participants experienced significant reductions in systolic (27.5 mm Hg) and diastolic (9.1 mm Hg) blood pressure, and HbA1c (23.1 mmol/mol) (all p<0.001). In study 3, 90% of patients with elevated body mass index achieved 5-10% weight loss, and 82% reported an increase in moderate or higher physical activity levels.

PCC and PHM integration led to substantial improvements in glycaemic control, blood pressure, weight management and physical activity. These findings support the adoption of community-based PCC models to manage chronic conditions effectively and improve public health outcomes.

Chronic excessive ethanol intake is known to exacerbate the progression of type 2 diabetes mellitus (T2DM). The overactivation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, which triggers gasdermin D (GSDMD)-mediated pyroptosis of pancreatic β-cells, is a crucial pathway in the deterioration of T2DM. However, the effects of ethanol on this process and the underlying mechanisms are not well understood. This study aimed to investigate the impact of ethanol exposure on pyroptosis of pancreatic β-cells and to determine whether it involves the NLRP3/GSDMD signaling pathway using high glucose (HG)-treated INS-1 cells and T2DM mice. In vitro, ethanol exposure induced a time- and concentration-dependent increase in pyroptotic bodies, excessive generation of reactive oxygen species (ROS), and overactivation of the NLRP3/GSDMD signaling in HG-treated INS-1 cells. However, inhibition of NLRP3 or caspase-1 significantly alleviated these adverse effects. In the T2DM mouse model, ethanol feeding worsened glucose and lipid metabolic disorders, decreased insulin sensitivity, and resulted in abnormal islet morphology and β-cell pyroptosis, along with overactivation of the NLRP3/GSDMD signaling pathway in pancreatic tissues. Importantly, these effects of ethanol were absent in Nlrp3^-/- mice. Our findings demonstrate that excessive ethanol exposure can exacerbate pyroptosis of pancreatic β-cells in T2DM mice by activating the NLRP3/GSDMD signaling pathway, thereby accelerating disease progression. This study provides new insights into the mechanisms underlying the harmful effects of ethanol on T2DM and highlights the potential therapeutic role of targeting the NLRP3/GSDMD pathway in ethanol-associated diabetes complications.

In type 2 diabetes, platelets are likely affected by impaired long-term glycaemic control, but such pathophysiological links are poorly understood. This study thus compares platelet reactivity (i.e. agonist-evoked platelet reactions) in vitro with glycosylated haemoglobin (HbA1c), a measure commonly used for monitoring long-term metabolic control of type 2 diabetes. Elders with type 2 diabetes (n = 35) were divided according to HbA1c into groups (HbA1c-low and high) consisting of 17 and 18 subjects, respectively. For estimating mitochondria disintegration, a flow cytometer determined mitochondrial transmembrane potentials after whole blood agonist stimulation. The activating agents used were α-thrombin (10 μM) and collagen (0.15 μg/mL). The same apparatus analysed the fibrinogen receptor activity, lysosomal exocytosis (surface lysosomal-associated membrane protein 1), and platelet procoagulant characteristics (membrane-attached annexin V) after stimulation. In type 2 diabetes, after in vitro agonist stimulation, platelet mitochondria injury was higher in the HbA1c-high group. The fibrinogen receptor, lysosomal secretion, and the creation of procoagulant platelets proved to be uninfluenced by HbA1c.

The effective implementation of the FGM contributes to achieving glycemic control, reducing hypoglycemic and hyperglycemic decompensations as well as enhancing patient self-management and improving their perception of quality of life. The aim of our study was to evaluate the glycemic control in type 2 diabetes patients after having implemented FGM in clinical practice.

Current patients with type 2 diabetes treated in our unit were monitored (FGM). A Structured Therapeutic Education Program was carried out and glycemic control variables were compared at the start and after 3 months of treatment.

A total of 36 patients were included (mean age of 67.8±12.4 years, 36.11% female, diabetes duration 21.5±2.12 years and a previous median glycated hemoglobine of 7.55%). Comparing the baseline data and the measures at 3 months, it was found a decrease in both glucose management indicator (GMI) (0.15% [0.40;0.30], P 0,537) and the coefficient of variation (CV) (1,42±4,66%, P 0,07), as well as an increase in time in range (TIR) (3,44±14.72%, P 0,169). Furthermore, a decrease in time in hyperglycemia >250mg/dl was observed (2,00% [-6,50;0,00] P 0,001).

FGM has led to a favorable advance in the management and glycemic control in patients with type 2 diabetes.

Most patients with large B-cell lymphoma (LBCL) progressing after CAR-T therapy experience poor survival and lack standardized treatment strategies. Prognostic tools are needed to guide decision-making at relapse. The Post-CAR Prognostic Index (PC-PI), recently proposed by Iacoboni et al., combines five routine clinical variables to stratify outcomes after CAR-T failure: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to progression (< 4 months). We evaluated the PC-PI in a retrospective multicenter study including 125 LBCL patients relapsing or refractory after axicabtagene-ciloleucel or tisagenlecleucel, treated between 2019 and 2023 across 16 Italian centers belonging to the Fondazione Italiana Linfomi network. Median overall survival (OS) was 4.9 months, with 6- and 12-month OS rates of 44.9% and 28.5%, respectively. The PC-PI discriminated prognosis effectively: high-risk patients had a median OS of 1.8 months, intermediate-high 2.2, intermediate-low 8.7, while in the low-risk group median OS was not reached (p<0.0001). Results remained consistent after excluding patients receiving only palliative care. Post-progression therapy markedly influenced survival: patients receiving active treatment achieved a median OS of 7.3 months versus 0.7 without further therapy (p<0.0001). Bispecific antibodies conferred the best outcomes (HR 0.44, p=0.02), with 6- and 12-month OS rates of 90% and 55%. Our findings confirm the prognostic value of the PC-PI and support its use in clinical practice as a tool for risk-adapted management of LBCL after CAR-T failure.

Upper tract urothelial carcinoma (UTUC) poses diagnostic challenges due to its anatomical complexity and limited accessibility.

This prospective multicenter study (NCT05043662) evaluated the diagnostic performance of UroCAD, a novel non-invasive assay based on chromosomal copy number variation (CNV) analysis, in 244 patients with suspected UTUC or benign upper urinary tract conditions.

Urine samples were analyzed for arm-level chromosomal aberrations (|Z-score|≥ 3.21), with histopathology as the reference standard. UroCAD demonstrated excellent diagnostic accuracy: sensitivity 91.0%, specificity 97.0%, and overall accuracy 93.4%. Performance was consistent across tumor locations (renal pelvis: 96.8%, ureter: 86.4%) and grades (high-grade: 93.5%, low-grade: 76.2%). Compared to urine cytology, UroCAD showed significantly higher sensitivity (91.2% vs. 52.9%, P < 0.001). CNV profiling revealed grade-associated patterns, with high-grade tumors frequently exhibiting amplifications on 1q and 8q. The extent (MaxZ) and number (CountZ) of chromosomal alterations correlated positively with tumor grade, supporting UroCAD's potential utility in molecular grading.

The UroCAD test demonstrates robust diagnostic performance for UTUC detection with high specificity and high sensitivity. The consistent performance across various clinical scenarios and the identification of specific chromosomal alteration patterns support its potential as a valuable clinical tool for both initial diagnosis and treatment monitoring. These findings warrant larger-scale validation studies to confirm its utility in routine clinical practice.