Dietary inflammatory load, quantified using the Dietary Inflammatory Index (DII), reflects pro-inflammatory dietary patterns that may contribute to impaired bone health. However, population-based evidence regarding the association between dietary inflammatory potential and bone mineral density (BMD) among adults with type 2 diabetes (T2D) remains limited, particularly regarding potential sex-specific differences. This cross-sectional study assessed the association between the DII and low BMD (osteopenia or osteoporosis) in adults with T2D. Data from the 2007 to 2010, 2013 to 2014, and 2017 to 2018 cycles of the National Health and Nutrition Examination Survey were analyzed. DII scores were computed from 22 dietary components; participants lacking BMD or DII data were excluded. Low BMD was defined from femoral neck and lumbar spine BMD, with osteoporosis and osteopenia both classified into a single category ("low BMD"). Weighted logistic regression was used to examine the relationship between DII score and low BMD overall and according to sex, adjusted for age, race/ethnicity, body mass index, socioeconomic variables, and clinical confounders. Subgroup analyses, interaction tests, and sex-stratified correlation analyses were performed for consistency. Data from 1768 adults with T2D, of whom 798 had low BMD, were included. Higher DII scores were significantly associated with an increased risk for low BMD in women (femoral neck: odds ratio = 2.575, 95% confidence interval = 1.484-4.468, P = .001; lumbar spine: odds ratio = 1.864, 95% confidence interval = 1.111-3.129, P = .018), with no significant association observed in men. A significant interaction according to sex was detected (P for interaction = .02); however, no interactions were found for age or body mass index. Findings suggested that an elevated DII is independently associated with low BMD in women with T2D. Clinically, sex-specific, anti-inflammatory dietary strategies may help mitigate the risk for low BMD in this population.

The relationship between different autoimmune diseases (ADs) and pancreatitis has been reported in epidemiological studies. This study systematically investigated the causal effects of ADs factors on pancreatitis using Mendelian randomization (MR). We selected 17 common ADs as exposures from the largest genome-wide association study dataset in Europe. The outcome variables included acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced acute pancreatitis, and alcohol-induced chronic pancreatitis. A variety of analytical methods were used to comprehensively evaluate the causal relationship between ADs and various types of pancreatitis, with sensitivity analyses, including Cochran's Q test and MR-Egger intercept test performed to verify the reliability of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation. Genetically predicted type 1 diabetes (OR = 1.032, 95% CI = 1.008-1.056, P = .0086) and ulcerative colitis (OR = 1.065, 95% CI = 1.012-1.121, P = .0151) were associated with an increased risk of AP. primary sclerosing cholangitis (OR = 1.080, 95% CI = 1.013-1.153, P = .0194) increased the risk of CP. Reverse MR analysis suggested a potential protective causal association between alcohol-induced acute pancreatitis and hashimoto's thyroiditis (OR = 0.962, 95% CI = 0.936-0.989, P = .0056), although this finding should be regarded as suggestive because it did not remain statistically significant after Bonferroni correction. Sensitivity analysis did not detect horizontal pleiotropy or heterogeneity. Genetic evidence supports a causal link between type 1 diabetes, ulcerative colitis , and AP, as well as between primary sclerosing cholangitis and CP. This analysis provides new insights into ADs as risk factors for pancreatitis, but further experimental research is needed to explore the potential causal relationships between these factors.

Thyroid dysfunction and diabetes mellitus (DM) are two common endocrine disorders that share overlapping metabolic pathways. While several studies have explored the association between thyroid function and DM, findings have been inconsistent. Specifically, both elevated and suppressed thyroid-stimulating hormone (TSH) have been variably reported as risk or protective factors for diabetes, and the contribution of thyroid autoimmunity (thyroid peroxides antibody, TPOAb) to diabetes risk remains particularly contested across study populations. This study aimed to evaluate the relationship between thyroid function markers-TSH, free thyroxine (free T4), and TPOAb - and the presence of diabetes in Korean adults. This cross-sectional study analyzed data from 4910 adults aged 19 years or older who participated in the Korea National Health and Nutrition Examination Survey (KNHANES VI) from 2013 to 2015. Serum levels of TSH, free T4, and TPOAb were measured, and DM was defined based on fasting glucose levels, use of antidiabetic medication, or self-reported diagnosis. As KNHANES does not classify diabetes by etiological subtype, the DM group predominantly reflects type 2 diabetes, consistent with its overwhelming predominance among Korean adults; type 1 diabetes could not be separately identified. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for diabetes across thyroid function categories, with subgroup analyses by age and sex. High TSH levels were significantly associated with an increased risk of diabetes (OR = 2.82; 95% CI: 1.26-6.32), especially in men under 65 years (OR = 5.10; 95% CI: 1.65-15.77). Low TSH levels were inversely associated with diabetes risk (OR = 0.35; 95% CI: 0.15-0.86). Low free T4 levels were also linked to an increased risk (OR = 2.08; 95% CI: 1.16-3.75), particularly in younger men. TPOAb positivity showed no significant overall association with diabetes, although a potential protective trend was observed in older men. Altered thyroid function, especially high TSH and low free T4 levels, is associated with increased diabetes risk in Korean adults. These findings suggest the clinical utility of thyroid function screening in diabetes risk assessment and highlight the need for further longitudinal research.

Canine diabetes mellitus (DM) is a relatively common endocrinopathy, and it requires dedication and commitment from an owner to care for a diabetic pet. This study aimed to describe treatment and monitoring habits, perceived owner and veterinary concerns when treating and monitoring a diabetic dog, as well as triggers for and risk of euthanasia in diabetic dogs among Norwegian veterinarians. A questionnaire was designed and made available online.

A total of 125 veterinarians completed the survey. According to the data collected, the cumulative incidence risk for treatment initiation was 71.6% (95% CI 63.2, 80.6), suggesting that the respondents started most of the diabetic dogs seen in their practice on treatment. The majority of the respondents reported that all female entire diabetic dogs were neutered near the time of diagnosis. Main veterinary treatment concerns identified were difficulties in achieving rapid and adequate control. Main respondent-perceived owner concerns were cost and injecting their diabetic dog. About 60% of respondents had never used a continuous glucose monitor. Of respondents having used such monitors, half had experienced owners changing the insulin dose themselves, without consulting a veterinarian. Nearly one third of the veterinarians recalled that issues related to monitoring contributed directly to euthanasia of a diabetic dog in their care. The estimated one month and one year cumulative risk of euthanasia in dogs started on insulin therapy found in our study were 11.5% (95% CI 8.3, 14.6) and 26.9% (95% CI 22.0, 31.8), respectively. In our study population, respondents working in large cities were more likely to report a high probability of starting treatment than respondents in small cities and rural areas. Respondents in small cities and rural areas were also more likely to report medium and high risk of euthanasia compared to respondents in large cities, respectively. Veterinary-perceived owner triggers for euthanasia were dogs' quality of life, monitoring, and owners' lifestyle changes. For the respondents themselves, comorbidities were the leading factor reported for recommending euthanasia.

This questionnaire-based study describes perceived treatment concerns, and reasons for and estimates of euthanasia risk in dogs with DM, based on the experiences of veterinary practitioners working in Norway. The results highlight important aspects of the treatment and monitoring of dogs with DM, as well as triggers for euthanasia. Further investigations into the aspects identified could be useful to improve the overall care for diabetic dogs.

Gut microbial dysbiosis has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetes, but the metabolic effects of candidate probiotic strains across this disease continuum remain incompletely understood. Based on the validation of disease-associated microbial patterns in a clinical cohort, Lactobacillus acidophilus as selected as a candidate strain, and its effects were systematically investigated across multiple complementary models, including Western diet, fructose-palmitate-cholesterol diet, high-fat diet, and leptin-deficient ob/ob mice. L. acidophilus supplementation attenuated hepatic steatosis and inflammatory injury in multiple complementary models and improved glucose tolerance in ob/ob mice. These effects were accompanied by reduced hepatic expression of pro-inflammatory cytokines, changes in AMPK-associated signaling, decreased expression of lipogenic (Srebf1 and Acc) and gluconeogenic (Pepck and G6pc) genes, and increased Ppara expression, suggesting coordinated regulation of glucose and lipid metabolism. Transcriptomic profiling further indicated that L. acidophilus influenced broader metabolic networks, including altered expression of Lpin1 and enrichment of pathways related to nutrient sensing and metabolic regulation. In addition, L. acidophilus supplementation altered gut microbial community structure in mouse models, while human cohort analyzes revealed context-dependent microbial patterns involving Lactobacillus, Akkermansia, and butyrate-producing Firmicutes across metabolic disease states. Collectively, these findings suggest that L. acidophilus may improve metabolic dysfunction through coordinated hepatic metabolic regulation and gut microbial modulation, supporting its potential as a probiotic candidate for MASLD and diabetes-associated metabolic disease.

To describe the properties of a newly approved oral glucagon-like peptide-1 receptor agonist for the treatment of obesity.

A literature search of MEDLINE and SCOPUS was performed without date range exclusions using the search terms orforglipron and obesity. Additional articles were identified from review of clinical trial bibliographies and product monograph.

Two phase 1 studies in healthy individuals and in patients with type 2 diabetes mellitus and 4 phase 2/3 clinical trials specifically evaluating orforglipron use for obesity were identified for analysis, using no date exclusion criteria.

Orforglipron was evaluated in 4 phase 2/3 trials regarding its efficacy for weight loss. These trials showed a mean 7.1% to 10.6% placebo-adjusted weight reduction with orforglipron. Adverse events seen with its use were primarily gastrointestinal.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Orforglipron provides an oral weight management option that is potentially more effective than liraglutide, similarly effective compared with semaglutide, and less effective than tirzepatide. As a non-injectable option that does not require strict oral administration parameters, orforglipron has advantages in certain patient populations.

Orforglipron is a potentially useful addition for the treatment of obesity, but it still requires additional data on efficacy in treatment of obesity-related comorbidities for full comparison.

Diabetic ulcers (DUs) are severe and prevalent complications of type 2 diabetes, characterized by impaired macrophage efferocytosis and sustained chronic inflammation within the wound microenvironment. Pachymic acid (PA) is a natural triterpenoid with potent anti-inflammatory and immunomodulatory properties. This research is aimed at exploring whether PA facilitates healing of DUs by activating the MEK/ERK/TGFβ1 signaling axis to restore macrophage efferocytosis.

In vitro, cell viability was evaluated using CCK-8 assay. An inflammatory macrophage model was established via LPS/IFN-γ induction to assess the impact of PA on reactive oxygen species (ROS) and proinflammatory mediator levels. Macrophages were cocultured with apoptotic cells to evaluate efferocytosis. Transcriptome sequencing, bioinformatics analyses, and RT-qPCR validation were conducted on PA-treated macrophages to explore the core regulatory networks, whereas western blot was utilized to verify the underlying proefferocytotic mechanisms. In vivo, a diabetic wound (DW) mouse model was established and treated with PA. Western blot, immunofluorescence, and histological staining were performed to evaluate macrophage polarization, the activation of the MEK/ERK/TGFβ1 pathway, angiogenesis, and the expression levels of efferocytosis-related proteins.

In vitro experiments demonstrated that PA exhibited minimal cytotoxicity, significantly reduced ROS levels, and suppressed the secretion of proinflammatory mediators in macrophages while enhancing their ability to engulf apoptotic cells. Transcriptomic profiling, RT-qPCR validation, and protein-protein interaction network analyses revealed that PA's regulatory targets were enriched in efferocytosis and the MEK/ERK pathway. In the DW mouse model, PA treatment alleviated inflammatory cell infiltration, promoted collagen deposition and angiogenesis, improved the SPOT skin wound score, and accelerated wound closure. Both in vitro and in vivo analyses confirmed that PA upregulated the expression of P-MEK1/2, P-ERK1/2, and TGFβ1, and key efferocytosis receptors, which drove the phenotypic transition of wound macrophages from a proinflammatory state to an anti-inflammatory and restorative state.

PA upregulated the expression of vital efferocytosis receptors by activating the MEK/ERK/TGFβ1 signaling axis, enhancing macrophage efferocytosis, and alleviating local oxidative stress. This study elucidated the mechanism of PA in treating DUs, providing a theoretical foundation for its clinical translation as a novel drug to promote DW healing.

Asthma exacerbations (AE) impose a significant burden on children and the healthcare systems, highlighting the need for objective biomarkers and functional assessment tools.

This study aimed to evaluate serum endocan levels and respiratory function parameters during AE and the post-recovery (PR) period, and to compare the results with healthy controls.

In this prospective longitudinal observational study, children aged 6-18 years were evaluated during AE (n = 66), 1 month after recovery (PR group, n = 54), and as age- and gender-matched healthy controls (HC, n = 50). All participants underwent spirometry, impulse oscillometry (IOS), and serum endocan measurement.

Serum endocan levels were significantly higher in the AE group than in the PR and HC groups [267.33 (186.68-370.20) vs. 133.07 (38.26-226.78) and 118.11 (42.93-180.20) pg/mL, respectively; P < 0.001]. Spirometric indices, including zFEV1, zFVC, zFEV1/FVC, and zFEF25-75, were significantly lower in the AE group than in both comparison groups (all P < 0.05). Compared to healthy controls, children in the AE group exhibited higher R5-20, Fres, and AX values and lower zX20 values (all P ≤ 0.002). R5-20 remained significantly higher during AE than in the PR period (P = 0.038), while spirometric indices showed significant improvement after recovery (all P < 0.05). Notably, despite normalization of spirometric parameters and serum endocan levels, the PR group continued to exhibit higher R5-20 and AX values and lower zX20 values than healthy controls (all P < 0.05), suggesting persistent small-airway dysfunctioning. Serum endocan levels showed weak-to-moderate negative correlations with zFEF25-75, zFEV1, and zFEV1/FVC (Spearman's rho = -0.306, -0.291, and -0.223, respectively; all P ≤ 0.013).

These findings suggest that serum endocan is associated with airway dysfunctioning and may reflect disease activity during pediatric AE, while IOS may provide additional information regarding persistent small-airway involvement after recovery.

Although immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), the benefit of continuing immune checkpoint inhibitors (ICIs) after disease progression (PD) remains uncertain. This real-world study assessed the efficacy and safety of second-line immunotherapy in ES-SCLC patients using propensity score matching (PSM).

ES-SCLC patients who received second-line treatments following first-line chemoimmunotherapy at Zhejiang Cancer Hospital from January 2019 to December 2023 were included. Clinical baseline characteristics were collected and balanced. The efficacy and safety of patients who continued to receive second-line immunotherapy were compared with those who did not.

A total of 187 patients were analyzed. The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 8.5 months (95% CI: 7.1-9.9) and 3.3 months (95% CI: 2.5-4.1), respectively. After PSM, each group included 76 patients. No significant differences in OS (median OS: 8.3 vs. 7.8 months; HR, 0.97; 95% CI: 0.68-1.39; p = 0.87) or PFS (median PFS: 3.45 vs. 3.1 months; HR, 1.07; 95% CI: 0.77-1.49; p = 0.69) were observed between the rechallenge and non-rechallenge groups. Subgroup analysis suggested in an exploratory manner that immunotherapy rechallenge was associated with poorer outcomes in non-smokers (mOS: 8 vs. 16.6 months; HR, 2.9; 95% CI: 1.1-7.9; p = 0.004). The rate of all-grade immune-related adverse events (irAEs) was higher in the rechallenge group (36.8% vs. 17.1%).

Rechallenge with immunotherapy after first-line chemoimmunotherapy may not demonstrate a significant survival benefit in ES-SCLC patients, particularly among never smokers, and may lead to more frequent irAEs.

For locally advanced oesophageal carcinoma, multimodal therapy is the standard of care, but prognosis remains poor. Obesity has risen markedly in the last decades. The impact of obesity on response to neoadjuvant treatment remains unclear. This study evaluates the association between body mass index (BMI) and histopathological tumour regression following neoadjuvant therapy in oesophageal cancer.

We performed an analysis using the prospective database from the DGAV|registry oesophageal surgery provided by the German Society for General and Visceral Surgery (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie, DGAV). The primary outcome was histopathological tumour regression grade by the Becker classification. The primary explanatory variable was BMI. Descriptive statistics were followed by uni- and multivariate regression analyses adjusted for tumour histology, neoadjuvant regimen, age, sex, ECOG status, comorbidities, dysphagia and weight loss. Associations were evaluated using a multivariate regression (partial proportional odds) model.

Six hundred and forty-seven patients were included, comprising 432 adenocarcinomas (including AEG I/II) and 215 squamous cell carcinomas (SCC). After adjustment for clinical and tumour-related covariates, higher BMI was independently associated with a favourable histopathological response: No association was observed for the transition to Becker grade ≥ 1b; however, higher BMI was associated with reduced odds of Becker grade ≥ 2 (OR 0.97, 95% CI 0.94-1.00, p = 0.04) and Becker grade ≥ 3 (OR 0.93, 95% CI 0.90-0.96, p < 0.001). In addition, SCC, absence of dysphagia, radiochemotherapy and low ECOG score were independently associated with favourable regression, whereas no independent associations were observed for age, sex, diabetes status, comorbidities or pretherapeutic weight loss.

Analysis of the German DGAV|registry revealed that higher BMI was significantly associated with improved histopathological tumour regression following multimodal therapy for oesophageal cancer. These findings suggest potential differences in tumour biology among patients with elevated BMI, underscoring the need for further mechanistic investigation.