To examine the role of maternal lipid metabolism before and during pregnancy in the development of gestational diabetes mellitus, and to evaluate its clinical implications for maternal and offspring outcomes.

Shifts in lipid metabolism represent key physiologic adaptations of pregnancy, and, when dysregulated, may contribute to the pathogenesis of gestational diabetes. Lipid abnormalities typically precede conception, underscoring a continuum between pre-pregnancy metabolic health and pregnancy outcomes. Low HDL-C, elevated triglycerides, and small dense LDL-C particles have been repeatedly associated with increased gestational diabetes risk across several cohorts and meta-analyses, although the strength of these associations varies according to study design and population characteristics. During pregnancy, women with gestational diabetes display a reproducible lipid phenotype defined by higher triglycerides, lower HDL-C, and increased triglycerides/HDL-C ratios. These perturbations exacerbate insulin resistance, trigger inflammatory and oxidative stress pathways, and act as contributors to disease progression rather than secondary consequences of hyperglycemia. Clinically, maternal dyslipidemia has been associated with adverse outcomes including pre-eclampsia, gestational hypertension, severe hypertriglyceridemia-related pancreatitis, and neonatal complications such as macrosomia, large-for-gestational-age birth weight, and preterm delivery. Beyond pregnancy, lipid disturbances have been linked to unfavourable cardiometabolic trajectories in the offspring, suggesting transgenerational effects.

Integrating mechanistic and clinical evidence, this review emphasizes the need for early lipid assessment, personalized nutritional counseling, and targeted interventions alongside glucose-centered care to improve maternal and offspring outcomes.

In patients presenting with intestinal symptoms who undergo colonoscopy with mucosal sampling, the pathologist plays a central role in identifying the underlying etiology in order to guide appropriate clinical management. However, common intestinal symptoms such as diarrhea are shared by a broad spectrum of conditions, including infectious diseases, functional disorders (e.g., irritable bowel syndrome), inflammatory bowel disease (IBD), drug-induced injury, and metabolic disorders (e.g., diabetes mellitus). Although serological biomarkers may support the diagnostic workup, they are frequently insufficient to establish a definitive diagnosis. Moreover, endoscopic examination may fail to detect significant mucosal abnormalities even when histology reveals disease-specific patterns, as occurs in lymphocytic and collagenous colitis (i.e., microscopic colitis). In this complex diagnostic landscape, histomorphological evaluation represents a crucial element, allowing integration of microscopic findings with clinical and endoscopic data to reach an accurate interpretation. In recent years, accumulating evidence has demonstrated that similar histological patterns of intestinal injury-such as IBD-like architectural and inflammatory changes or eosinophil-rich infiltrates-may be associated with different underlying etiologies. This overlap is particularly relevant in patients treated with novel oncologic therapies, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and emerging treatments such as chimeric antigen receptor T-cell (CAR-T) therapy. In addition, in daily practice, pathology request forms often lack essential clinical, endoscopic, and laboratory information, further increasing the risk of diagnostic misinterpretation and inappropriate disease attribution. To address these challenges, the Italian Group of Digestive Disease Pathology (GIPAD) proposes a pattern-based histological approach for reporting mucosal damage in patients with colitis. In this first paper, we focus on non-chronic patterns of mucosal injury and discuss their principal differential diagnoses, with the aim of supporting standardized reporting and improving clinicopathological correlation.

Given the differences between Chinese T2DM patients and those of other ethnicities, understanding the metabolic contributions in this population is essential. This study aimed to identify T2DM-associated metabolic biomarkers through clinical untargeted metabolomics and mendelian randomization (MR).

This study included 120 Chinese participants, including 60 patients with T2DM and 60 control subjects. We employed ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for non-targeted metabolomics analysis of plasma metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify T2DM-related metabolites. Integration of metabolomics and MR data identified novel key biomarkers for T2DM.

LC-MS/MS-based untargeted metabolomics identified 71 up-regulated and 37 down-regulated metabolites in the Chinese T2DM patients. In MR analysis, 52 metabolites exhibited causal associations with the risk of T2DM. Integrating metabolomic analysis with genetic evidence-based causal inference collectively confirmed that higher adrenic acid (AdA) were associated with increased risk of T2DM and positively correlated with fasting blood glucose (FBG). The main metabolic impacted pathways were unsaturated fatty acids biosynthesis, linoleic acid metabolism.

Increased plasma AdA level was associated with higher FBG and an elevated risk of T2DM, suggesting that AdA represents a probable biomarker for T2DM.

To examine postural control in people with type 2 diabetes mellitus (T2DM) with and without diabetic neuropathy (DN) using center of pressure (CoP) measures under varying sensory and cognitive conditions.

In this cross-sectional study, adults aged ≥ 40 years with T2DM for at least one year. Neuropathy was classified as severe peripheral neuropathy (DPN) or autonomic neuropathy (DAN), defined by vibration perception threshold ≥ 50 V, ≥2 abnormal cardiac autonomic reflex tests, or orthostatic hypotension. Postural control was assessed by CoP^Area and CoP^Velocity under different sensory and cognitive conditions. Regression analyses were adjusted for demographic factors, physical performance, and fall-associated medication. Exploratory analyses were performed by neuropathy subtype.

99 participants were included, 49 with DN and 50 without. The DN group was older (66.8 vs. 60.8 years) and more often male (75.5% vs. 52%). DN was associated with greater CoP^Area (β = 0.56, p = 0.006). Exploratory analyses suggested larger CoP^Area in participants with DAN alone (β = 0.76, 95% CI 0.36-1.16) or combined with DPN (β = 0.70, 95% CI 0.13-1.34), whereas DPN alone was not associated with CoP^Area.

DN was linked to impaired postural control, with indications of differences by neuropathy subtype. CoP assessment may help identify people with T2DM at increased risk of falls.

Diabetic wounds are a common complication and a debilitating condition of diabetes mellitus, which are characterized by chronic inflammation, persistence, and aggravation. Evidence suggests the beneficial influence of Loganin on diabetic complications and inflammation. However, the effectiveness of Loganin on diabetic wounds remains uninvestigated.

Network pharmacology was applied to identify the potential targets of Loganin in diabetic wound healing. Employing a streptozotocin (STZ)-induced diabetic mouse model, we conducted evaluations pertaining to the effects of Loganin on wound healing and assessment of macrophage-related phenotypes via ELISA, immunohistochemistry, Western blot and qPCR. In vitro, we used J774A.1 mouse macrophage cell line and induced differentiated Th17 cells for experiments. Molecular docking, biotin-labeled pull-down assays and cellular thermal shift assays were applied to investigate direct mechanisms.

Loganin topical application accelerated wound healing in diabetic mice, reduced local inflammation, and inhibited NLRP3 inflammasome activation. The IL-17/NF-κB signaling pathway was suppressed by Loganin, thus inhibiting NLRP3 inflammasome. In particular, Loganin inhibited IL-17 A/F production in Th17 cells and targeted the NF-κB p50 subunit in macrophages, thus blocking its nuclear translocation and pro-inflammatory activation.

Loganin may be considered as an adjuvant or a new therapeutic agent in the management of chronic non-healing diabetic wounds.

Hematopoietic stem cell transplantation (HSCT) is a critical treatment for non-Hodgkin lymphoma (NHL) but involves significant post-transplant risks. Frailty, measured by the Modified Frailty Index-11 (mFI-11), may influence outcomes.

We analyzed NHL patients undergoing autologous or allogeneic HSCT from the Nationwide Inpatient Sample (2016-2020). Frailty was defined by mFI-11, and outcomes included in-hospital mortality, unfavorable discharge, prolonged length of stay (LOS), complications, and costs. Multivariable regression models with stratification by age and Charlson Comorbidity Index were applied.

Of 2807 patients (ages 18-85), frail patients were older and had more comorbidities. In autologous HSCT, frailty was linked to higher mortality (2.02% vs. 0.27%, p < 0.001), increased unfavorable discharges (19.75% vs. 10.80%, p < 0.0001), and prolonged LOS (15.92% vs. 7.75%, p < 0.0001). Similar trends were observed in the allogeneic cohort.

Frailty predicts worse post-transplant outcomes in NHL patients undergoing HSCT, emphasizing the need for pre-transplant frailty screening.

Neoadjuvant therapy has become a cornerstone in the management of locally advanced rectal cancer (LARC). In this single-arm, open-label phase II study, we evaluated the efficacy and safety of total neoadjuvant chemotherapy (TNT) using a CapOX regimen combined with a programmed cell death protein 1 (PD‑1) antibody (sintilimab) and interleukin‑2 (IL‑2) in patients with microsatellite stable (MSS)/defining proficient mismatch repair (pMMR) LARC. A total of 33 patients, aged 18-75 years, with rectal tumors located within 12 cm from the anal verge and staged as cT3/4N_anyM0 or cT_anyN⁺M0, were enrolled. Patients received a regimen consisting of oxaliplatin, sintilimab, capecitabine, and IL‑2 administered in a three‑week cycle, with response evaluations performed after every two cycles. Following six cycles of treatment, 33 patients underwent radical surgery, achieving a 100% R0 resection rate. The pathological complete response (pCR) rate was 42.4% (95% CI: 25.68-59.16%) while the remaining 19 patients (57.6%, 95% CI: 41.07-74.09%) were assessed as having a partial response. The tumor regression grades (TRG) were, TRG1: 3 cases (9.1%, 95% CI: 1.90-25.97%), TRG2: 14 cases (42.4%, 95% CI: 26.27-60.38%), and TRG3: 2 cases (6.1%, 95% CI: 0.73-20.37%), respectively. Surgical safety reported as no cases of grade B/C anastomotic leakage or bowel obstruction. Adverse events (AEs) were manageable, with a 21.2% incidence of grade 3 events and no grade IV/V events or treatment‑related deaths. With a median follow‑up of 25.5 weeks, no recurrences were observed. Analysis of blood and tissue samples from patients with different treatment outcomes revealed significant activation of CD8⁺ T cells, NK cells, and M1 macrophage subsets in the tumor microenvironment of patients achieving pCR. These compelling data demonstrate promising efficacy with a favorable safety profile in MSS/pMMR LARC. These findings warrant studies to validate this regimen as a novel treatment paradigm for rectal cancer. ClinicalTrials.gov registration: NCT06108596.

Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of global cancer death. The process of epithelial-to-mesenchymal transition (EMT) is a key driver of early progression and metastasis in PDAC.

Our study aimed to explore the correlation between the expression of EMT markers and survival outcomes.

We conducted a retrospective longitudinal study on patients diagnosed with resectable PDAC between January 2005 and June 2019, with a 5-year follow-up for survival analysis. Immunohistochemical staining was performed to assess E-cadherin and vimentin expression. EMT was defined as the presence of high Vimentin (mesenchymal) expression combined with low E-cadherin (epithelial) expression. The study cohort included 135 patients with resectable PDAC, with 86 males (63.7%) and a mean age of 63.5 years (SD 10.1); most tumors were grade 2 (84, 64.6%). Cox regression analysis revealed that Vimentin expression (p = 0.005), positive margin (p = 0.008), and absence of metformin intake (p = 0.023) were independent predictors of poor OS. High Vimentin was associated with lower median OS (17.0 ± 4.4 vs. 25.8 ± 2.3 months, p = 0.037) and DFS (8.6 ± 1.2 vs. 13.0 ± 2.3 months, p = 0.014), compared to low Vimentin, and it was correlated with higher tumor grade (p = 0.028) and metastasis rate (p = 0.032). The poorest outcomes were observed when high Vimentin was coupled with low E-cadherin (median OS of 12.6 ± 4.7 vs. 24.5 ± 2.1 months, p = 0.038; median DFS of 9.5 ± 0.5 vs. 10.8 ± 2.1 months, p = 0.029), compared to the rest of the population.

Our findings showed that Vimentin overexpression and the EMT phenomenon are strongly associated with poor OS and DFS in resectable PDAC, underscoring their potential as prognostic biomarkers and therapeutic targets.

Cancer therapy-related cardiac dysfunction (CTRCD) is among the most important adverse effects of treatment of childhood cancer. In the EARLY study (Early detection of acute and early-onset cARdiovascuLar toxicity in children with cancer using a multiparametric approach), cardiac function in children treated for cancer was monitored during and shortly after treatment, using advanced echocardiography, electrocardiography, and cardiac magnetic resonance (CMR) techniques.

In this prospective pilot study, 100 children newly diagnosed with childhood cancer receiving anthracyclines as part of their cancer treatment were included. A subgroup of 30 children was included in the CMR sub-study. Echocardiography, electrocardiography, and CMR were performed before (T0), three and a half months after (T1), and one year after (T2) start of anthracycline treatment. In this article, we focus on the methodological aspects of the EARLY study, including patient enrollment and characteristics of the study cohort, as well as the feasibility of advanced echocardiography.

The last patient was included in August 2022. Follow-up for the last patient was finalized in August 2023. Follow-up was completed by 92% of the total study population and 97% of the CMR sub-study.

Protocol adherence was high (92%-97%) and a full collection of data on each included individual was achieved. Advanced echocardiography, i.e., 4D ejection fraction and global longitudinal strain, was feasible in 76% and 69% of measurements, respectively. Cardiac outcomes during and shortly after treatment, as well as associations with known risk factors for CTRCD, such as anthracycline dose, dose of radiotherapy involving the heart, childhood cancer disease profile, age at diagnosis and sex will be reported in a future publication. The feasibility of the study allows for future insight into the correlation between early-onset CTRCD and heart failure during long-term follow-up of childhood cancer patients.

ClinicalTrials.gov identifier: NL-OMON22737.

Recent studies have demonstrated the significance of gut microbiota in the colorectal cancer (CRC) pathogenesis. But their role in carcinogenesis remains to be established. Thus, we established a clinical cohort and the faecal samples from CRC and healthy control were collected. Our metagenomic analysis found that the presence of Parvimonas micra exhibited the most significant relationship with the occurrence of CRC. Increased colonisation of P. micra in CRC was validated with analysis of 1379 faecal metagenomes from eight public cohorts. Untargeted metabolomics subsequently identified an accumulation of phenyllactic acid (PLA) in faecal samples from CRC patients. Higher concentration of PLA was detected in the supernatant from our isolated P. micra. Whole-genome sequencing confirmed that a series of genes associated with PLA biosynthesis such as pdhD were observed in the P. micra genome. Importantly, both P. micra and PLA-induced carcinogenesis in Apc^Min/+ and azoxymethane/dextran sulphate sodium salt mice model. The roles of P. micra and PLA in CRC development were associated with DNA damage. Engineered Escherichia coli BL21 that encoded the heterologous pdhD from P. micra could also induce DNA damage. Mechanically, PLA-induced DNA damage and CRC carcinogenesis were significantly alleviated in Ahr^-/- mice. Aryl hydrocarbon receptor (AHR) inhibitor exhibited a therapeutic potential to reduce mice carcinogenesis. These findings established the role of P. micra and its metabolite, therefore providing diagnostic and therapeutic targets for treating CRC.