B7 homolog 3 protein (B7-H3), a member of the B7 checkpoint family, is aberrantly and consistently expressed on the membranes of various human cancer cells and is associated with poor prognosis. Emerging evidence also indicates that soluble B7-H3 (sB7-H3) correlates with adverse outcomes in multiple malignancies. In this study, we measured sB7-H3 levels in peripheral blood using an enzyme-linked immunosorbent assay (ELISA) from 100 newly diagnosed osteosarcoma (OTS) patients, both before and after neoadjuvant chemotherapy, and simultaneously assessed B7-H3 tissue expression via immunohistochemistry (IHC) analysis of surgical specimens. Our analysis showed significant associations between B7-H3 tissue expression and histopathological response to chemotherapy, with the H-score threshold > 75 identifying patients with particularly poor prognosis (p < 0.05). Although no significant correlation was observed between tissue and circulating B7-H3 expression, we found that lower baseline sB7-H3 levels (pre-sB7H3 < 21.2425 ng/mL) predicted poor clinical outcomes. By integrating sB7-H3 levels with established prognostic indicators, including metastatic status and lactate dehydrogenase (LDH) levels, we developed a comprehensive prognostic model that demonstrated strong predictive accuracy for survival outcomes. Notably, pre-sB7-H3 levels were significantly associated with good histological responses (p < 0.05). Longitudinal monitoring during treatment revealed that dynamic changes in sB7-H3 levels positively correlated with disease progression (p < 0.05) and inversely correlated with good histological responses (p < 0.05). These findings highlight serum sB7-H3 as a clinically valuable biomarker in OTS, providing prognostic information both at diagnosis and throughout the course of treatment in a relatively convenient manner.

With the increasing prevalence of diabetes, the incidence rate of diabetic kidney disease (DKD) has risen yearly in China. While traditional therapies like renin-angiotensin system blockers remain foundational, the treatment paradigm is rapidly evolving with the emergence of novel agents, including SGLT2 inhibitors, mineralocorticoid antagonists, endothelin receptor antagonists, and GLP-1 receptor agonists. This study aims to provide an overview of the changing landscape of drug clinical trials on DKD in mainland China from 2013 to 2023. Detailed information of drug trials for DKD registered on the National Medical Products Administration Registration and Information Disclosure Platform for Drug Clinical Studies was collected. A total of 50 trials for DKD were included. Bioequivalence trials accounted for the most significant proportion (48%), followed by phase II (22%), phase I (20%), and phase III (10%). Chemical drugs accounted for the largest proportion (92%), followed by traditional Chinese medicine/natural medicine (8%). There were 18 different drugs involved in the 50 trials with Irbesartan (n = 24, 48%) ranked first in the number of trials. The parallel-group design was primarily used (48%), followed by crossover design (46%). Randomization was used by almost all trials (92%). Of all trials, 44 (88%) were launched domestically, whereas only 6 (12%) were international multi-center trials. Drug trials showed an uneven geographical distribution. Despite the progress in DKD drug clinical trials in mainland China during recent years, innovative drug research and development still has a long way to go. These findings provide an evidence base for optimizing global-regional alignment in DKD innovation policy.

Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5-2 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer's disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.

Multicentre, retrospective, observational, new-user, active-comparator cohort study.

Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.

Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.

Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.

The study analysed 24 172 matched pairs for stroke outcomes (40 483 person-years in the SGLT2 inhibitor group and 39 363 person-years in the TZD group), 25 111 matched pairs for dementia (41 924 person-years in the SGLT2 inhibitor group and 40 726 person-years in the TZD group) and 25 237 matched pairs for AD (42 139 person-years in the SGLT2 inhibitor group and 40 895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95% CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95% CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95% CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.

SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.

Femoral fractures are high-impact injuries commonly arising from traffic collisions, falls, and other trauma mechanisms. Surgical site infection (SSI) following fixation remains a major postoperative complication, amplified by soft-tissue disruption, environmental contamination, and prolonged hospitalization. Evidence on how mechanism of injury (MOI) moderates SSI risk, pathogen distribution, and antimicrobial resistance (AMR) patterns in trauma populations remains limited.

We conducted a 5-year retrospective cohort study (2020-2024) at a tertiary trauma centre including all operatively managed femoral fractures. MOI categories comprised traffic accidents, falls, sports injuries, violence, work-related trauma, and firearm injuries. Demographic, clinical, surgical, and microbiological data were obtained from a prospectively maintained registry. SSI was defined according to the 2018 AO/EBJIS Fracture-Related Infection (FRI) consensus criteria. Group comparisons used χ² or Fisher's exact tests, and multivariable logistic regression identified independent predictors. Infection-related reoperation and 1-year mortality were assessed with survival analysis.

Of 2891 patients, 249 developed SSI (8.6%). Gram-negative organisms predominated, with A. baumannii accounting for most isolates across MOI groups, while S. aureus was more common in younger and sports-related injuries. Resistance testing showed persistently high multidrug resistance (MDR, 66.2%), with declining trends in extensively drug-resistant (XDR) phenotypes and carbapenem resistance over time. Independent predictors of SSI included ASA ≥ 3, diabetes mellitus, preoperative anaemia, and operative duration > 90 min. SSI markedly increased reoperation rates and more than doubled 1-year mortality.

MOI shapes both SSI risk and microbiological profiles following femoral fracture surgery. The dominance of Gram-negative organisms and high MDR burden highlight the need for MOI-specific prevention strategies and trauma-adapted antimicrobial stewardship.

Gestational diabetes mellitus (GDM) is the most common pregnancy complication globally, yet recommendations for the timing and onset of labour vary. Clinical practice guidelines (CPGs) aim to improve safety and quality by guiding decision making through evidence-based recommendations.

Scoping review with embedded guideline appraisal to assess the consistency of recommendations regarding the timing and onset of labour for women with GDM and whether variation was associated with guideline quality.

Databases (MEDLINE, CINAHL, EBSCO, Scopus, Embase, JBI Guidelines) and websites of relevant professional organisations were searched.

Guidelines and consensus statements published from 2015 to January 2025, available in English from high-income countries, were included.

Guideline quality was assessed using the AGREE-II tool, and recommendations were analysed descriptively.

Of 1422 records screened, 24 CPGs met the inclusion criteria. The quality of the included CPGs varied, with inconsistent applicability and stakeholder involvement (mean AGREE-II domain scores 55%), developmental rigour (43%), and editorial independence (37%). On the basis of the AGREE-II scores, only 3 CPGs were recommended for use without modifications. Even among higher quality guidelines, recommendations for the onset and timing of labour varied, from 37 to 40+ 6 weeks.

Considerable variation exists with regard to the quality of CPGs and recommendations about the timing of birth for women with GDM. These findings highlight the importance of shared decision making and the need for further research to assist women and their maternity care providers in discussing optimal birth timing.

Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by proximal muscle weakness and pathognomonic cutaneous manifestations. Recognition in patients with skin of color can be delayed due to atypical presentation of classic rashes. A 59-year-old woman with type 2 diabetes mellitus and hypertension presented with progressive weakness, dyspnea, palpitations, edema, and significant unintentional weight loss. Initial evaluation revealed elevated transaminases and troponin, and she was managed for suspected autoimmune myocarditis. On readmission, she had hyperpigmented and violaceous patches on the chest, lower abdomen, and thighs and erythema with tenderness of the distal fingers and cuticles. Serologic testing was positive for ANA and anti-Mi-2 antibody, confirming dermatomyositis. She was treated with intravenous immunoglobulin and systemic corticosteroids, resulting in clinical improvement and discharge to a rehabilitation facility. Dermatomyositis has an estimated incidence of 1-6 per 100,000 in the United States, with increased prevalence among women and patients of African ancestry. Recognition of DM in skin of color is often delayed, as erythematous eruptions may appear as hyperpigmented or violaceous lesions, leading to diagnostic uncertainty. This delay can contribute to significant morbidity and recurrent hospitalizations. Increasing diversity in dermatology education and clinical resources is essential to improve recognition and outcomes.

Arterial calcification is the principal pathological marker of diabetic vascular complications. The principal causes of arterial calcification include hyperglycemia, advanced glycation end products (AGEs), and increased mechanical stress. Piezo1 is a mechanosensitive channel that is critically involved in vascular disease. The aim of this study is to clarify how Piezo1 activation promotes the calcification of cardiac smooth muscle cells through calcium-regulating mechanisms. In this study, the calcium-dependent regulatory mechanism of Piezo1 in a diabetic vascular calcification cell model was examined by using pharmacological and genetic approaches. Vascular smooth muscle-specific Piezo1 knockout mice were used to evaluate the protective function of Piezo1 in diabetic vascular calcification. In the diabetic mouse model, vascular calcification was associated with increased Piezo1 expression and enhanced O-GlcNAcylation. Piezo1 activation exacerbated calcification and O-GlcNAcylation in human coronary smooth muscle cells (HCASMCs), whereas Piezo1 inhibition alleviated these changes. Subsequent mechanistic studies revealed that Piezo1 interacts with Yes-associated protein 1 (YAP) and O-linked N-acetylglucosamine transferase (OGT) through calcium-dependent mechanisms, thereby enhancing the O-GlcNAcylation of runt-related transcription factor 2 (RUNX2) and promoting osteogenic development. Targeted Piezo1 ablation in smooth muscle reduced diabetes-related vascular calcification, increased vascular compliance, and restored regular molecular expression. This study demonstrated that Piezo1 augments OGT activity via a calcium-dependent YAP activation pathway, promoting the O-GlcNAcylation of Runx2, thereby advancing the osteogenic differentiation of HCASMCs and ultimately aggravating diabetic vascular calcification. Inhibiting the Piezo1 signaling pathway offers a novel approach for mitigating diabetic vascular complications.

Exenatide, the first glucagon-like peptide-1 receptor agonist (GLP-1RA), exerted multiple beneficial effects, including stimulating insulin secretion, slowing gastric emptying, and improving insulin resistance (IR). Our previous work demonstrated that the peroxisome proliferator-activated receptor delta (PPARδ) gene (PPARD) polymorphisms correlated with exenatide monotherapy efficacy, possibly due to the pivotal role of PPARδ in regulating IR. Specifically, PPARδ has been shown to modulate the nucleotide-binding domain and leucine-rich repeat pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of pyroptosis, thereby participating in the regulation of this inflammatory cell death pathway. However, the underlying mechanisms by which exenatide ameliorated hepatic IR in patients with type 2 Diabetes Mellitus (T2DM) remained incompletely understood. Herein, we found that exenatide suppressed pyroptosis and ameliorated hepatic IR; furthermore, it could bind to PPARδ and upregulate PPARδ protein expression both in vitro and in vivo. Notably, PPARδ knockdown abolished the protective effects of exenatide against pyroptosis and hepatic IR, whereas pharmacological activation of PPARδ enhanced these beneficial effects. Moreover, T2DM patients carrying the AA genotype at PPARD rs3777744 and exhibiting higher baseline homeostasis model assessment of insulin resistance (HOMA-IR) showed a superior response to exenatide. Collectively, our findings revealed that exenatide ameliorated hepatic IR by suppressing pyroptosis via PPARδ, underscoring the potential of PPARD rs3777744 as a biomarker for personalized exenatide therapy in T2DM.

Socioeconomic (SE) factors have been shown to mediate racial and ethnic disparities in adult cancer mortality. However, evidence in pediatric cancer is limited, especially at finer geographic levels.

Evaluate the mediating effect of socioeconomic status (SES) and persistent poverty in racial and ethnic disparities in childhood cancer mortality using census tract-level data.

Data were obtained from the 2006-2020 SEER Incidence Data with Census Tract Attributes Database and included children 0-19 years. Neighborhood-level SES was measured using a composite variable with five categories. Census tracts were classified as persistently poor if 20% or more of the population lived below the poverty level for 30 years. Cause-specific Cox proportional-hazard models were used to examine the association of race and ethnicity with cancer mortality, adjusting for age, gender, stage at diagnosis, cancer type, and rurality. A weighted approach mediation analysis was performed in R4.1.3.

Among 96,665 included cases, 19.95% of children lived in the lowest SES quintile, and 12.23% lived in areas with persistent poverty. The distribution of SES and persistent poverty varied across race and ethnicity. Specifically, 9.79% of White children lived in the lowest SES neighborhoods compared to 33.77% of Black and 32.48% of Hispanic children. In addition, 4.83% of White children lived in persistent poverty compared to 21.38% of Black and 21.30% of Hispanic children. Compared to White children, the risk of cancer death was higher among Black (aHR: 1.53; 95% CI: 1.45-1.62), Hispanic (aHR: 1.17; 95% CI: 1.12-1.22), and Asian (aHR: 1.24; 95% 1.15-1.33) children. The proportion mediated by SES was 13.50% for Black, 29.3% for Hispanic, and 37.58% among AI/AN children. The proportion mediated by persistent poverty was 6% for Black, 12.79% for Hispanic, and 17.47% for AI/AN children.

SES and persistent poverty significantly contributed to racial and ethnic differences in pediatric cancer mortality.

Gallbladder cancer is an aggressive malignancy with disproportionately high incidence in North India. Most patients present at advanced stages, limiting curative options. This study aimed to prospectively evaluate outcomes of multimodal treatment-including neoadjuvant chemotherapy, surgery, and palliative chemotherapy-in a high-volume endemic center.

In this prospective observational cohort, 1,500 newly diagnosed gallbladder cancer patients were enrolled between September 2023 and May 2024. Clinical details, treatment intent, type of therapy, and survival outcomes were systematically recorded. Patients were stratified into three groups: neoadjuvant chemotherapy for borderline resectable disease, upfront curative surgery, and palliative chemotherapy for metastatic disease. Kaplan-Meier analyses were performed for overall survival (OS).

Of 1,500 patients, 1,203 (80.2%) presented with metastatic disease. Among 75 patients who received neoadjuvant chemotherapy, 61.3% progressed and only 12.7% could undergo curative surgery. Overall, 116 patients underwent surgical exploration and 92 received definitive surgery, achieving a 1-year overall survival of 88.5%. Of 768 patients planned for palliative chemotherapy, 294 received ≥ 1 cycle, with a median overall survival of 5 months.

In this real-world prospective cohort, surgery remains the only treatment associated with meaningful survival, while neoadjuvant chemotherapy and palliative chemotherapy yielded limited benefit. Early detection and standardized treatment pathways are urgently needed in endemic regions.