Methotrexate (MTX) remains the cornerstone in the treatment of psoriasis. However, concerns about its potential to contribute to liver fibrosis or cirrhosis have remained. We aimed to define the relationship between MTX exposure or other risk factors with liver fibrosis in patients with psoriasis.

We examined the liver stiffness measurement (LSM) in patients with psoriasis from a single center between 2019 and 2024. At the time of LSM, baseline clinical, demographic, comorbidities, laboratory, and medication information were obtained. Psoriasis patients were stratified into two groups: one that had not been exposed to MTX (no MTX), and another that had been exposed to MTX for more than 6 months. Liver fibrosis was measured by transient elastography (TE) and FIB 4. We used a cut-off of ≤7.9 kPa to rule out advanced fibrosis and ≥11.5 kPa to rule in cirrhosis, respectively.

Of the 483 individuals with psoriasis, 101 (21%) patients showed TE values ≥ 7.9 kPa. Sixty-five (22.3%) of MTX-exposed group showed TE ≥ 7.9 kPa compared to thirty-six (19.3% with no-MTX (P = 0.33). On multivariate logistic regression analysis, the only significant factor linked to stiffness ≥ 7.9 was type 2 diabetes mellitus (T2DM) (adjusted odds ratio = 2.8; 95% CI 1.44-5.43; P = 0.002). Liver fibrosis did not correlate with age, MTX cumulative dose, hyperlipidemia, obesity, or hypertension in multivariate analysis, despite some of these factors showing significance on univarite analysis.

T2DM, not cumulative methotrexate dose, was associated with liver stiffness. These findings reinforce the need to revise methotrexate monitoring guidelines to incorporate transient elastography, particularly for patients with metabolic risk factors.

4-hydroxy isoleucine (4-HIL), a potent glucose-lowering agent and insulin secretagogue, is widely available in nutraceutical market as fenugreek seed extract formulations. This study aims to elucidate the oral pharmacokinetics (PK) of 4-HIL in healthy human volunteers to standardize its dose and dosing regimen, ensuring its potential for effective diabetes management.

Twelve healthy volunteers received a single oral administration of 150 mg of 4-HIL as fenugreek seed extract tablets. Caplillary blood samples were collected at various time points within 24 h and plasma levels of 4-HIL were quantified using liquid chromatography-tandem mass spectrometry. In vitro studies on 4-HIL pharmacodynamics, derived from the literature, were used to calculate the half-minimal effective concentration (EC50). PK assessments based on compartmental modelling and dosage simulation studies were conducted using PKsolver and ModVizPOP, respectively. The PK simulation included three distinct dosage regimens (150 mg thrice daily, 225 mg twice daily, or 450 mg once daily) to evaluate EC50 level attainment.

The best-fit was observed with a two-compartmental model, with maximum 4-HIL plasma concentration (Concentration maximum, 2.42 ± 0.61 µg/mL) observed at 0.5 h (Time maximum). The derived mean EC50 of 4-HIL, needed to reduce blood glucose, was 1.50 ± 0.31 µg/mL. The PK simulation study indicated that daily intake of 450 mg 4-HIL in all three tested dosing regimens had maintained EC50 levels more than 18 h for glucose-lowering effects.

The optimal 4-HIL dose of 450 mg/day up to three divided dosing regimens has proven effective and hence may be considered for future diabetic trials.

This study aims to evaluate the therapeutic effect of Alpiniae Oxyphyllae Fructus-Saposhnikoviae Radix(AOF-SR) in a diabetic kidney disease(DKD) mouse model, explore its potential mechanism in regulating the NOD-like receptor protein 3(NLRP3) inflammasome via phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway, and provide new theoretical support for traditional Chinese medicine(TCM) intervention in DKD. Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), the active ingredients and potential targets of AOF-SR were screened and its molecular mechanisms were investigated through molecular docking, molecular dynamics simulations, and experimental validation. The db/db mice were randomly divided into four groups: model group, low-dose AOF-SR group, high-dose AOF-SR group, and canagliflozin group. The db/m mice served as normal group. After one week of acclimatization, the mice underwent drug intervention. Starting from one week after treatment, body weight, blood glucose levels, and 24-hour urinary protein(24hUP) were measured every two weeks. After 13 weeks of administration, tissue collection and indicator detection were performed. Blood glucose, 24hUP, urinary microalbumin(mAlb), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were determined. Pathological changes in kidney tissue were observed using hematoxylin-eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of serum IL-1β, IL-18, and caspase-1, while RT-qPCR was employed to measure the mRNA expression levels of IL-1β, IL-18, caspase-1, and NLRP3. Western blot was used to assess the protein expression levels of NLRP3, PI3K, p-Akt, Akt, p-mTOR, and mTOR. Network pharmacology analysis indicated that wogonin, pinocembrin, hancinol, and kaempferol were the core compounds for drug treatment of the disease. Molecular docking and molecular dynamics simulations showed that core compounds, particularly wogonin, could specifically bind to PIK3R1, thereby regulating the PI3K/Akt/mTOR pathway. The experimental results indicated that both low and high doses of AOF-SR and canagliflozin significantly reduced blood glucose, 24hUP, mAlb, Scr, and BUN levels in db/db mice, while improving kidney pathological damage and inflammatory cell infiltration. Moreover, the treatments reduced the mRNA expression levels of caspase-1, IL-1β, and IL-18 in the kidneys of db/db mice, as well as the secretion of these factors in the serum. The drugs also inhibited the mRNA and protein expression levels of NLRP3 in the kidneys of db/db mice and decreased the protein levels of PI3K, p-Akt/Akt, and p-mTOR/mTOR. In conclusion, AOF-SR may improve kidney inflammation in DKD mice by regulating the PI3K/Akt/mTOR signaling pathway and inhibiting NLRP3 inflammasome activation.

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.

Krill oil (KO), a source of EPA, DHA, phospholipids, and astaxanthin, has emerged as a promising functional ingredient to maintain skeletal muscle health. However, its protective role against type 2 diabetes mellitus (T2DM)-induced sarcopenia has remained poorly characterized. Hence, the present study aimed to investigate the protective effects and underlying mechanisms of KO against sarcopenia in both a T2DM mouse model induced by the combination of streptozotocin and high-fat, high-sucrose diet, and a C2C12 myotube atrophy model induced by high glucose (HG), advanced glycation end products (AGEs), and lipopolysaccharide (LPS). Incorporation of 1.5% KO (w/w) in the diet of mice with T2DM for 24 weeks significantly enhanced insulin sensitivity, lowered blood glucose levels, and decreased serum and muscle AGEs levels. Additionally, dietary KO markedly ameliorated intestinal barrier dysfunction in mice with T2DM, as evidenced by the improvement of intestinal pathological injuries, the decrease of serum and muscle LPS levels, and the restoration of the expression of tight junction proteins. Dietary KO also significantly mitigated skeletal muscle mass and strength loss in mice with T2DM, and alleviated HG/AGEs/LPS-induced C2C12 myotube atrophy. Moreover, dietary KO effectively reduced the overproduction of pro-inflammatory cytokines and ROS accumulation in the skeletal muscle of mice with T2DM and in HG/AGEs/LPS-stimulated C2C12 myotubes. Furthermore, dietary KO alleviated T2DM-induced skeletal muscle protein turnover impairment both in vivo and in vitro, as demonstrated by increased de novo protein synthesis via activating the PI3K/Akt/mTOR signaling pathway, and inhibited excessive protein degradation through inactivating the FoxO3a- and NF-κB-mediated up-regulation of MAFbx and MuRF1. Overall, our findings suggested that KO might have therapeutic potential against T2DM-induced sarcopenia.

The prevalence of asymptomatic pancreatic cysts is increasing due to advances in imaging techniques. Among these, intraductal papillary mucinous neoplasms (IPMNs) are most common, with potential for malignant transformation, often necessitating close follow-up. This study evaluates novel MRI techniques for the assessment of IPMN.

From May to December 2023, 59 patients undergoing abdominal MRI were retrospectively enrolled. Examinations were conducted on 3-Tesla scanners using a Deep-Learning Accelerated Half-Fourier Single-Shot Turbo Spin-Echo (HASTE_DL) and standard HASTE (HASTE_S) sequence. Two readers assessed minimum detectable lesion size and lesion-to-parenchyma contrast quantitatively, and qualitative assessments focused on image quality. Statistical analyses included the Wilcoxon signed-rank and chi-squared tests.

HASTE_DL demonstrated superior overall image quality (p < 0.001), with higher sharpness and contrast ratings (p < 0.001, p = 0.112). HASTE_DL showed enhanced conspicuity of IPMN (p < 0.001) and lymph nodes (p < 0.001), with more frequent visualization of IPMN communication with the pancreatic duct (p < 0.001). Visualization of complex features (dilated pancreatic duct, septa, and mural nodules) was superior in HASTE_DL (p < 0.001). The minimum detectable cyst size was significantly smaller for HASTE_DL (4.17 mm ± 3.00 vs. 5.51 mm ± 4.75; p < 0.001). Inter-reader agreement was for (к 0.936) for HASTE_DL, slightly lower (к 0.885) for HASTE_S.

HASTE_DL in IPMN imaging provides superior image quality and significantly reduced scan times. Given the increasing prevalence of IPMN and the ensuing clinical need for fast and precise imaging, HASTE_DL improves the availability and quality of patient care.

Question Are there advantages of deep-learning-accelerated MRI in imaging and assessing intraductal papillary mucinous neoplasms (IPMN)? Findings Deep-Learning Accelerated Half-Fourier Single-Shot Turbo Spin-Echo (HASTE_DL) demonstrated superior image quality, improved conspicuity of "worrisome features" and detection of smaller cysts, with significantly reduced scan times. Clinical relevance HASTEDL provides faster, high-quality MRI imaging, enabling improved diagnostic accuracy and timely risk stratification for IPMN, potentially enhancing patient care and addressing the growing clinical demand for efficient imaging of IPMN.

Laser interstitial thermal therapy (LITT) is a minimally invasive option for the management of a variety of intracranial pathologies, including radiographically progressive tumor following stereotactic radiosurgery. Although LITT has been increasingly accepted in recent years, little is known regarding selection and outcomes for patients of diverse backgrounds, particularly at centers specializing in central nervous system (CNS) metastases.

Patients receiving their index LITT treatment for brain metastasis at a single center from 2015 to 2023 were retrospectively reviewed. Patient demographics and geospatial data were used to compare differences in receipt of LITT by race or ethnicity, survival outcomes, and clinical trial enrollment.

From 2015 to 2023, 137 patients harboring 146 target lesions presented for LITT. One hundred and six patients (77.3%) were non-Hispanic White (NHW); of Hispanic or non-White (HNW) patients, 25 (18.2%) were Black or African American, 5 (3.6%) were Asian, and 1 (0.7%) was Hispanic or Latino. Among HNW patients, women more frequently received LITT (p = 0.022), with skin cancers being a more frequent indication among NHW patients (P = 0.019). NHW patients traveled a median of 62.0 (6.2-1045.9) miles to receive LITT vs. 25.9 (1.31-238.3) miles for HNW patients (p = 0.001). There was parity in procedural outcomes across groups. In multivariate analyses, post-LITT overall survival was predicted by pre-LITT KPS (P = 0.0007) and recurrent tumor on biopsy (P = 0.0002), while probability of clinical trial enrollment was less among those of female sex (P = 0.049), HNW race/ethnicity (P = 0.041), or external referral status (P = 0.035).

Patient sex, systemic disease histology, and distance from a treating center may differentially influence presentation for LITT according to underlying race/ethnicity. However, patients successfully treated in multidisciplinary CNS metastasis centers experience excellent post-procedural outcomes. Such centers should enact measures to ensure equitable clinical trial enrollment.

Most women diagnosed with breast cancer (BC) survive treatment and become long-term survivors. This study examines the association between long-term survival of female BC patients and clinical factors, socio-economic determinants, healthcare utilization, and drug use.

This retrospective population-based survival study uses linked cancer registry data, claims, and social security data at the individual level for all Belgian women diagnosed with invasive BC in 2010 (n = 9982). Ten-year survival probabilities were computed by using Kaplan-Meier and relative survival curves. A Weibull mixture cure model was employed to perform multivariable analysis.

The population consisted of women with early-stage (75.0%), locally advanced (13.1%), and metastatic BC (5.9%). The overall 10-year unadjusted survival was 68.2% [95% confidence interval (CI), 67.1%-69.3%], with decreasing survival in older women. However, survival was lower in women age <40 years compared with those aged 40-60 years. Multivariate analysis revealed that age was associated with long-term survivorship (odds ratio, 0.919; 95% CI, 0.918-0.919). Women receiving multimodal treatment (surgery followed by adjuvant radiotherapy and systemic treatment) were more likely to become long-term survivors compared with women receiving other treatments. Lastly, beneficiaries of increased reimbursement had lower odds of long-term survivorship.

Our study highlights the association between long-term survivorship in women diagnosed with invasive BC and factors such as age at diagnosis, treatment scheme, and entitlement to increased reimbursement. It is crucial to inform clinicians and policymakers on the appropriate use of mixture cure models, as their results can substantially impact healthcare decision-making. Furthermore, tailored BC screening strategies are essential to reduce social inequalities and mortality disparities.

Supportive care needs may increase in women with metastatic breast cancers concerning disease burden. The study's purpose was to determine the supportive care needs of women with metastatic breast cancer. The study was conducted in a cross-sectional design between January and December 2022. The sample of the study consisted of 92 women with metastatic breast cancer who met the inclusion criteria. Data were collected using the Individual Descriptive Information Form and the Supportive Care Needs Scale. A significant majority of the women with metastatic breast cancer reported having supportive care needs. The participants' supportive care needs were as follows: 93.5% for physical and daily life, 88% for spiritual/psychological needs, 86% for healthcare system and information, 56.5% for sexuality and 43.5% for patient care and support. This study determined the supportive care needs of women with metastatic breast cancer and revealed that the majority of patients have support needs related to physical, psychological, access to information, sexuality and patient care. The findings emphasise the necessity for individualised care processes and the importance of nurses taking an active role in symptom management, psychological support and information services. The effectiveness of digital health solutions and multidisciplinary care approaches should be investigated to ensure the creation of evidence-based health policies. It is recommended that future studies evaluate the changing care needs of patients in the long term, thereby contributing to the development of evidence-based health policies.

The purpose of this study is to present the nationwide disease burden and survival of nasopharyngeal carcinoma (NPC) in Sweden. The subcohort from the Stockholm-Gotland region was included to investigate the prevalence of Epstein-Barr virus (EBV) in NPC and to describe pattern of relapse.

This population-based nationwide study included patients diagnosed with NPC in Sweden during 2008-2021. The series was retrieved from the Swedish Head and Neck Cancer Register. Age at diagnosis, sex, tumor histopathology, stage, treatment intent, treatment, radiation dose, follow-up time, time to relapse, and site of relapse were recorded. The Stockholm-Gotland region series was used to obtain an updated histopathological analysis including EBV status and to analyze site of relapse.

The nationwide study cohort comprised 399 patients, 33% were female. Mean age at diagnosis did not differ between the sexes: 56.3 years for females, 57.5 years for males. Seventy-one percent presented with Stage III or IV. The 5-year overall survival (OS) was 73.2%. In the regional cohort, 73.9% were EBV positive. In the competing risk analysis, the cumulative incidence of distant metastatic relapse was higher than that of local and/or regional relapse at 5 years (18.7% vs. 12.4%). However, the confidence intervals were wide, and the difference should be interpreted with caution.

The survival outcome in our study seems comparable to previous studies in nonendemic countries. There was a high percentage of EBV-positive tumors compared with the previous studies in nonendemic countries.