The progressive decline in functional β-cell mass represents a fundamental, unmet challenge in type 2 diabetes (T2DM) management. Dorzagliatin (HMS5552), a fourth-generation, dual-acting, and glucose-dependent glucokinase activator (GKA), offers a distinct mechanistic approach that aims to move beyond symptomatic glycemic control toward potential glucose sensor modulation. This review critically synthesizes the development of dorzagliatin, designed to overcome the hypoglycemia and tachyphylaxis of earlier GKAs. While its unique allosteric mechanism enables synchronized restoration of insulin secretion and hepatic glucose metabolism, we critically evaluate its clinical positioning. Observational data from the DREAM study suggest sustained drug-free glycemic maintenance; however, we emphasize that these findings do not yet meet the rigorous 2021 American Diabetes Association/European Association for the Study of Diabetes consensus definition of "diabetes remission" and require validation through randomized withdrawal trials. Furthermore, we address the critical absence of long-term cardiovascular outcomes trials (CVOTs) and the theoretical concerns regarding hepatic de novo lipogenesis. We also propose a synergistic framework for combining dorzagliatin with sodium-glucose cotransporter-2 inhibitors to counteract compensatory endogenous glucose production, positioning it as a precision-driven component in the evolving T2DM therapeutic landscape. Should future CVOTs demonstrate safety and efficacy, GKAs like dorzagliatin could potentially be integrated into treatment guidelines, possibly as a "sensor-calibrator" for a subset of patients identified through metabolic and genetic phenotyping. However, it must be emphasized that no CVOT data are currently available for dorzagliatin.

Vasoplegic syndrome following cardiopulmonary bypass (CPB) is a major cause of postoperative circulatory failure in cardiac surgery and is associated with increased morbidity and mortality. Traditionally, vasoplegia has been attributed to systemic inflammation, endothelial dysfunction, excessive nitric oxide production, and pathological vasodilation. However, these mechanisms alone do not fully explain the marked variability in vasopressor responsiveness observed in clinical practice. Increasing evidence suggests that vasoplegia may result not only from depletion of endogenous vasopressors, but also from receptor desensitization and impaired intracellular signaling involving catecholamines, arginine vasopressin (AVP), and angiotensin II (Ang II).

A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, supplemented by citation tracking and manual cross-referencing. Literature was selected qualitatively according to its relevance to endogenous vasopressor physiology, GPCR signaling and desensitization, endothelial and glycocalyx dysfunction, extracorporeal circuit biocompatibility, and vasoplegic syndrome after cardiac surgery. Fifty-one publications representing the key clinical, experimental, translational, and physiological evidence informing these themes were included in the final narrative synthesis; this number represents the literature selected for qualitative discussion rather than the yield of a systematic-review screening process.

The available evidence suggests that CPB profoundly alters endogenous vasopressor pathways through systemic inflammation, oxidative stress, endothelial activation, ischemia-reperfusion injury, and prolonged adrenergic stimulation. These mechanisms may contribute to depletion of endogenous vasopressors as well as receptor downregulation, desensitization, and uncoupling of intracellular signaling pathways. Alterations involving vasopressin V1/V2 receptors, β-adrenergic receptors, and the renin-angiotensin system may all participate in vasopressor refractoriness. Increased activation of the ACE2/Ang-(1-7) counter-regulatory axis may further promote vasodilatory pathways, particularly in patients with obesity, diabetes mellitus, and heart failure. Emerging evidence also suggests that multimodal vasopressor strategies, including vasopressin and Ang II supplementation, may be more effective than isolated catecholamine escalation in refractory vasoplegia. In severe cases, non-conventional therapies such as Methylene Blue may restore vascular tone independently of classic vasopressor receptor pathways.

Vasoplegia after CPB may represent a complex endocrine and receptor-mediated disorder rather than a purely vasodilatory state. The interaction between endogenous vasopressor depletion, receptor dysfunction, and altered intracellular signaling may explain the development of catecholamine-refractory shock after cardiac surgery. A better understanding of these mechanisms could support more individualized and physiologically guided vasopressor strategies aimed at preventing receptor exhaustion and improving hemodynamic management in cardiac surgical patients.

To measure the prevalence of unruptured intracranial aneurysms (UIAs) in Chinese adults aged 35-75 years and establish a model to identify individuals with UIAs.

This cross-sectional survey enrolled adults aged 35-75 years from October 2023 to February 2025. Participants were recruited from three randomly selected communities across two urban and one suburban districts in Beijing, China, and received MR angiography. All images were initially reviewed by attending neuroradiologists and subsequently confirmed by senior neurointerventionalists. A logistic regression model identified risk factors, and a nomogram was developed and evaluated using area under the curve (AUC).

Of 5,120 potentially eligible residents, 4,711 (92%) were included after exclusions. The median age was 57 (IQR, 50-61) years and 2,576 (55%) were women. The observed MRA-based prevalence of UIAs was 9.2% (95% CI, 8.3-10.0%). Multivariate logistic analysis revealed that older age (adjusted OR, 1.03; 95% CI, 1.02-1.04), female sex (adjusted OR, 1.33; 95% CI, 1.08-1.63), family history of intracranial aneurysm or subarachnoid hemorrhage (adjusted OR, 2.36; 95% CI, 1.77-3.12), hypertension (adjusted OR, 1.65; 95% CI, 1.22-2.12), and diabetes mellitus (adjusted OR, 1.63; 95% CI, 1.33-2.00) were independently associated with an increased risk of UIAs. The FASH-D model based on clinical parameters performed well in determining the probability of having UIAs (AUC, 0.86; 95% CI, 0.84-0.89).

The MRA-based prevalence of UIAs was approximately 9%. The FASH-D model may help identify individuals with a higher probability of having a prevalent UIA, but external validation is required.

Dynapenic abdominal obesity (AO) is a recognized risk factor for hospitalization, disability, and mortality.

To examine the association between AO, dynapenia, and their coexistence with cardiometabolic risk factors in non-dialysis patients with chronic kidney disease.

A cross-sectional study was conducted with 91 patients at a nutrition and nephrology outpatient clinic in Bahia, Brazil. Adult and elderly individuals were classified into four groups based on handgrip strength and waist circumference: 1) non-AO/non-dynapenic (NAO/ND), 2) non-AO/dynapenic (AOD) (NAO/D), 3) AO/ND, and 4) AOD. Cardiometabolic risk was assessed via demographic, clinical, lifestyle, anthropometric, and biochemical parameters. Kruskal-Wallis, ANOVA, Chi-square tests, and Poisson regression were used for analysis.

The prevalence of AO/ND, NAO/D, and AOD was 58.2%, 38.5%, and 18.7%, respectively. In adjusted models, AO/ND was associated with increased body mass index (prevalence ratios [PR]: 1.15; 95% confidence intervals [CI]: 1.04-1.27). NAO/D was associated with hyperphosphatemia (PR: 1.77; 95% CI: 1.06-2.94). AOD was associated with diabetes mellitus (PR: 4.7; 95% CI: 1.44-15.7) and smoking (PR: 5.7; 95% CI: 1.26-25.5).

AO, dynapenia, and their coexistence were significantly associated with cardiometabolic risk factors in patients with early-stage chronic kidney disease, underscoring the importance of regular adiposity and muscle strength assessment in clinical practice.

To systematically summarise prediction models for sarcopenia in patients with type 2 diabetes mellitus (T2DM), appraise their methodological quality and reporting, and synthesise their discriminative performance.

PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang and VIP were searched from inception to 22 December 2025 for observational studies developing and/or validating multivariable models (≥2 predictors) for sarcopenia or low muscle mass in adults with T2DM. For studies reporting the area under the receiver operating characteristic curve (AUC), random- or fixed-effects meta-analyses were conducted to pool AUCs for training, internal validation and external validation datasets.

Twenty-six studies published between 2020 and 2025 were included, mostly cross-sectional or retrospective studies from China, with one based on US NHANES data. Most models used logistic regression; a few applied machine learning methods. Predictors commonly included age, sex, anthropometric indices, diabetes duration and control, biochemical and nutritional indicators, and muscle-related measures. Internal validation was frequently performed, whereas external validation was limited. Seventeen studies contributed training-set AUCs (pooled AUC 0.885, 95% CI 0.858-0.913; I² = 93.10%), and eleven contributed internal validation AUCs (pooled AUC 0.859, 95% CI 0.812-0.905; I² = 94.90%). Only two studies contributed external validation AUCs for pooling, yielding a pooled AUC of 0.945 (95% CI 0.923-0.966; I² = 0.00%); this result should be interpreted cautiously because of the very limited external validation evidence.

Existing prediction models for sarcopenia or low muscle mass in T2DM patients show promising discrimination, but limitations in analysis methods, reporting and external validation may affect their robustness and generalisability. Future work should strengthen methodological rigor and reporting in line with PROBAST and TRIPOD to facilitate reliable clinical use.

Plant by-products, often considered as waste in various agricultural and food processing industries, have emerged as a valuable source of natural antidiabetic or antihyperglycemic compounds. These compounds, derived from plant materials that would otherwise be discarded, have the potential to mitigate the global burden of diabetes and offer sustainable solutions for glycemic control. Prominent groups of natural antidiabetic compounds found in plant by-products are polyphenols, as well as bioactive proteins and peptides. In addition, agro-industrial residues such as wheat bran, oat husks, and fruit peels are excellent sources of carbohydrates that can be incorporated into functional foods to help manage diabetes. In addition to their antidiabetic potential, plant by-products contribute to sustainability and waste reduction by turning materials that would otherwise be discarded into valuable resources. Furthermore, the utilization of natural antidiabetic compounds from waste materials promises to improve diabetes management and promote a more sustainable food industry. The paper will address the valorization of agro-industrial by-products as natural sources of antiglycemic compounds, including an economic analysis and exploration of different raw material sources. It will present both the advantages and the key challenges associated with the biological activity, metabolism, bioavailability, and toxicological profiles of these compounds, as well as their economic and environmental implications. Furthermore, the review will highlight the prospects for automating this process through the application of artificial intelligence (AI), which may facilitate greater standardization and efficiency in future development.

This population-based study aimed to investigate the association between neighborhood deprivation and the incidence and mortality of lung cancer in patients with asthma.

This nationwide cohort study included 596,215 individuals aged ≥ 25 years with asthma who were followed from 1997 to 2018 in Sweden. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence and mortality associated with neighborhood deprivation. All models were stratified by sex and adjusted for individual-level characteristics, including age, education level, sociodemographic factors, and comorbidities.

Neighborhood deprivation was independently associated with both lung cancer incidence and mortality in patients with asthma, even after adjustment for individual-level characteristics. In fully adjusted models, compared with individuals living in low-deprivation neighborhoods, those in high-deprivation neighborhoods had a significantly elevated risk of lung cancer incidence (HR = 1.37) and mortality (HR = 1.40), with more pronounced associations observed in women. Histological subtype analyses revealed differential patterns: high deprivation was associated with increased risks of adenocarcinoma (HR = 1.19) and large cell carcinoma (HR = 1.58), whereas squamous cell carcinoma (HR = 1.75) and small cell carcinoma (HR = 1.65) showed increased risks in both moderate- and high-deprivation neighborhoods.

Neighborhood deprivation may be a critical social determinant of lung cancer incidence and mortality among patients with asthma, with effects varying by age, sex, and histological subtype. Targeted interventions in deprived communities could consider prioritizing high-risk groups, individuals with low educational attainment, and those with comorbid chronic obstructive pulmonary disease.

Recurrence remains a major cause of treatment failure after curative-intent therapy for resectable gastric and gastroesophageal junction adenocarcinoma. Clinicopathological staging, pathological response, serum tumor markers, and imaging incompletely identify patients with molecular residual disease (MRD). Circulating tumor DNA (ctDNA) has therefore emerged as a minimally invasive biomarker for perioperative risk stratification, response assessment, postoperative MRD detection, and recognition of molecular recurrence before radiographic relapse. In gastric and gastroesophageal junction cancer, postoperative ctDNA positivity has shown the most reproducible association with recurrence and survival, while serial studies indicate that early clearance during neoadjuvant therapy, persistence after preoperative therapy, and residual ctDNA after surgery or adjuvant chemotherapy represent distinct molecular states. However, several barriers remain: assay heterogeneity, variable sampling windows, clonal hematopoiesis, low shedding in diffuse-type and peritoneal-predominant disease, limited negative predictive value, and the absence of randomized evidence that ctDNA-guided intervention improves survival. Lessons from colorectal cancer are cautionary: randomized escalation and de-escalation trials have not uniformly translated strong prognostic validity into clinical utility. This review summarizes perioperative ctDNA evidence in resectable gastric and gastroesophageal junction adenocarcinoma, compares tumor-informed and tumor-agnostic platforms, examines peritoneal and molecular-subtype-specific limitations, and proposes a trial-ready framework for escalation, de-escalation, and molecular surveillance. At present, ctDNA is suitable for risk stratification and clinical-trial enrollment as an adjunct to, rather than a replacement for, conventional surveillance; it is not ready for routine treatment adaptation outside prospective studies.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy requiring multi-modality treatment. Radiotherapy (RT) may improve local control and resection rates, though evidence to support use across various stages of disease is mixed and evolving. This study sought to investigate international practice patterns and provider preferences for the use of radiotherapy in the multidisciplinary management of PDAC.

A 39-item electronic survey was distributed in 2025 through three sub-specialty organizations to providers who have recently treated PDAC.

A total of 176 PDAC providers from six continents completed the survey, with the majority practicing in Europe (n= 76, 43%) and North America (n= 62, 35%). Respondents included mostly surgeons (n= 143, 81%) with 81% (n= 142) practicing in academic centers. Nearly 1 in 5 respondents did not offer or consider any indication for neoadjuvant (n= 32, 19%) or adjuvant (n= 46, 30%) RT. The most commonly cited indication for neoadjuvant RT was for locally advanced disease (n= 88, 52%) and surgically unresectable disease (n= 86, 51%), while the use of adjuvant RT was primarily for positive surgical margins (n= 97, 63%) and positive nodal disease (n= 46, 30%).

In an international cohort of surgeons and radiation oncologists, there is substantial variation in perceptions of effectiveness, management preferences, and the propensity to utilize radiotherapy for PDAC. These results underscore the lack of strong evidence to support management, and the need for consensus guidelines and clinical trials to inform best practice.

Thoracic radiotherapy (RT) is linked to cardiovascular toxicity, but its impact on the cardiac conduction system, particularly the sinoatrial (SA) node, is poorly defined. We examined whether SA node radiation dose is associated with new-onset atrial fibrillation (AF), accounting for the competing risk of death. We retrospectively studied 84 lung cancer patients undergoing thoracic RT, stratified by maximum SA node dose (D_max) using an exploratory, data-derived threshold of 17.23 Gy. Cumulative incidence functions and Fine-Gray regression, treating death as a competing event, assessed AF risk. Median age was 68.5 years; median follow-up was 12.0 months. AF occurred in 9 patients (10.7%). The high-dose SA node group (>17.23 Gy) was significantly younger (65.5 vs. 70.0 years; P=0.010) with similar Mayo AF Risk Scores (P=0.821), yet had a higher 24-month cumulative incidence of AF (18.8% vs. 4.1%; Gray's test P=0.038). AV node D_max was not associated with AF but correlated with post-radiotherapy PR-interval prolongation (+14.1 ms; Spearman ρ=0.47, P=0.006). In an exploratory multivariable model adjusting for age, SA node D_max remained associated with AF (adjusted sHR 1.04 per 1-Gy; 95% CI 1.01-1.06; P=0.008), warranting cautious interpretation given the limited event number. In this hypothesis-generating, single-center cohort, higher SA node dose was associated with increased AF incidence independent of age, while AV node dose was linked to PR prolongation rather than AF. These preliminary findings require validation in larger, prospective, multicenter cohorts before the SA node can be considered a formal organ at risk in RT planning.