In Cross-Domain Few-Shot Learning (CD-FSL), models are required to identify novel classes while addressing domain discrepancies caused by visual style variations. Simple style transformations often fail to extend beyond the source domain’s distribution, and unrepresentative support samples in the target task may lead to ambiguous or biased decision boundaries. To address these challenges, a Style-Guided Source Data Augmentation and Target Feature Optimization (SSDATFO) approach is proposed. Specifically, Style-Guided Source Data Augmentation is introduced, employing Style Transformation and Source Data Augmentation techniques to create more challenging source data, thereby expanding the source domain’s style distribution. Target Feature Optimization is subsequently introduced, comprising two distinct modules. The Domain Attention Shift Transformation enhances low-magnitude feature channels, thereby reactivating target domain feature channels previously overlooked by the source domain-trained feature extractor. Additionally, the Task Category Differentiation Enhancement Transformation calibrates the features of support samples and eliminates the commonality component along both the task-specific and inter-class commonality directions for all features within the novel task, thereby acquiring more discriminative features. Extensive experiments on eight distinct target datasets demonstrate the efficacy of the proposed method, while comprehensive ablation studies and detailed visualization experiments elucidate its nuanced and compelling aspects.

Objectives Elevated resting heart rate (RHR) predicts mortality in middle-aged and older adults, primarily through cardiovascular disease (CVD). Whether RHR predicts mortality in young adults, which causes of death are involved and whether the association replicates are unclear. In young US adults, who fall below the starting age of current cardiovascular risk tools, we examined RHR and all-cause and cause-specific mortality across two cohorts.Methods We analysed 3291 adults aged 20–49 years from National Health and Nutrition Examination Survey (NHANES) 1999–2004 (primary cohort) linked to mortality through 2019 (median follow-up 17.8 years; 120 deaths) with replication in 8941 adults from NHANES III (1988–1994; 1317 deaths; median follow-up 27.6 years; temporal replication). RHR and heart rate reserve (HRR) were modelled per 10 beats per minute increment using Cox regression adjusted for demographic, lifestyle and comorbidity covariates.Results Each 10 beats per minute higher RHR was associated with higher all-cause mortality (primary cohort: HR, 1.26; 95% CI 1.07 to 1.50; validation: HR, 1.17; 95% CI 1.12 to 1.22). In the primary cohort most deaths (99 of 120) were non-CVD; the CVD-specific analysis was underpowered (21 deaths; HR, 1.15; 95% CI 0.77 to 1.71). In validation, RHR predicted non-CVD (HR, 1.17; 95% CI 1.11 to 1.23) and CVD (HR, 1.18; 95% CI 1.08 to 1.29) mortality about equally. The association strengthened with age, emerging by the early-to-mid 30 s in both cohorts, before the starting age of current risk tools. HRR, measured under submaximal conditions, was not associated with any outcome.Conclusions In young US adults, elevated resting heart rate, a free and routinely measured vital sign, predicts long-term mortality across two cohorts, marking broad survival vulnerability rather than cardiovascular risk alone. Detectable in the early-to-mid 30 s, below the starting age of current cardiovascular risk tools, resting heart rate may flag at-risk young adults before these tools apply. Submaximal HRR carried no prognostic value.

Purpose: Huatan Huoxue decoction (HTHXD) is effective in treating polycystic ovary syndrome (PCOS); however, its underlying mechanisms of action remain unclear. Methods: Gene targets were obtained through Mendelian randomization (MR) analysis using druggable genes from public databases and genome-wide association study data for PCOS from the FinnGen R12 database. These targets were integrated with the active ingredients and protein targets of HTHXD retrieved from the TCMSP and BATMAN-TCM databases for network pharmacology analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted. Core targets were validated using molecular docking. Experimental validation was performed using a letrozole-induced PCOS rat model treated with HTHXD, with key targets assessed via quantitative PCR (qPCR) and immunohistochemical staining. Results: MR analysis identified 131 proteins causally related to PCOS, of which 52 with strong associations remained after quality control. Network pharmacology analysis revealed 549 gene targets and 243 active ingredients in HTHXD. The intersection of these datasets identified four core targets for HTHXD in PCOS treatment (CA2, CASP3, SNCA, and TSPO). Molecular docking identified tanshindiol B, 4-methylenemiltirone, and danshenol B in Danshen and crocetin in leech as key active components. HTHXD substantially ameliorated polycystic ovarian morphology and reduced corpora lutea in PCOS model rats. CA2 expression was significantly upregulated in PCOS ovarian tissue (P < 0.0001), and markedly reduced after HTHXD treatment, consistent with immunohistochemical findings. Conclusion: CA2 may serve as a potential candidate gene associated with the therapeutic response to HTHXD in PCOS, with tanshindiol B and crocetin as major active components.

Maturity-onset diabetes of the young (MODY) is the most common form of monogenic diabetes, with genetic and clinical heterogeneity emerging as significant challenges. Despite growing scholarly attention to MODY research, the overall knowledge structure, research priorities, and developmental trends in this field have not yet been systematically integrated. To ensure comprehensive coverage and compatibility with bibliometric analysis tools, relevant publications on MODY were retrieved from the Web of Science Core Collection (WoSCC) database from 2006 to 2025. Employing bibliometric methods and tools such as CiteSpace, VOSviewer, Scimago Graphica, and Microsoft Excel, we conducted visual analyses of publication trends, country and regional collaboration, institutional distribution, author contributions, co-cited journals, co-cited references, and keywords. From 2006 to 2025, a total of 1,610 publications related to MODY were identified, showing an overall increasing trend over time. The United States of America (USA), the United Kingdom (UK), and China were the major contributors to this field, with close collaborative relationships, particularly between the USA and the UK. The leading contributors by country, institution, and author were the USA (391 publications), the University of Exeter (105 publications), and Sian Ellard and Andrew T. Hattersley (50 publications each). High-frequency keywords included “gene”, “monogenic diabetes”, “children”, “prevalence”, “glucokinase”, and “mutation”. In the co-citation analysis, the study by Shields BM published in 2010 showed the highest citation frequency. These findings indicate that MODY research has primarily centered on genetic mechanisms, clinical diagnosis, and precision management, with recent attention gradually moving toward functional genomics and individualized therapeutic strategies. MODY research has evolved into a multidisciplinary field that bridges biological mechanisms, clinical characterization, and translational application. Future studies should broaden population coverage and translate molecular findings into more precise diagnosis and individualized management.

Cardiac surgery, associated acute kidney injury (CSA-AKI), is a common and serious postoperative complication that adversely affects patient prognosis. Dexmedetomidine is widely used during cardiac surgery and has demonstrated renoprotective properties; however, its association with renal function recovery after CSA-AKI remains unclear. This study aimed to investigate the relationship between perioperative dexmedetomidine administration and renal function recovery in patients with CSA-AKI. This retrospective cohort study analyzed data from the Medical Information Mart for Intensive Care (MIMIC-IV) database between 2008 and 2022. Adult patients who developed AKI following cardiac surgery were included. Propensity score matching was applied to balance baseline characteristics between patients who received perioperative dexmedetomidine and those who did not. Logistic regression analysis assessed the association between dexmedetomidine use and renal function recovery. Subgroup analyses were conducted according to AKI stage and type of cardiac surgery, along with dose- and duration-based analyses. A total of 3,431 patients with CSA-AKI were included, of whom 1,019 received dexmedetomidine and 2,412 did not. Overall, 2,671 patients (77.85

This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of hesperidin supplementation on insulin resistance and sensitivity in adults. Two authors independently searched electronic databases, including PubMed, Scopus, Embase, Web of Science, and the Cochrane Library, from their inception to July 2025 for relevant RCTs. The quality of the included studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias. Heterogeneity among the included studies was evaluated using Cochrane's Q test and the I2 statistic. A meta-analysis of eligible studies was conducted using either fixed- or random-effects models, with the weighted mean difference (WMD) serving as the overall effect size. Pre-specified subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity. This meta-analysis included 16 studies, comprising 845 participants and assessing five outcome measures. We found that hesperidin supplementation significantly reduced the homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.43, 95%CI: -0.82, -0.03; p = 0.034) and increased the quantitative insulin sensitivity check index (WMD: 0.05, 95%CI: 0.01, 0.08; p = 0.005). However, no significant effects were observed on insulin, fasting blood glucose, or glycated hemoglobin A1c. Subgroup analyses indicated that supplementation with high-dose, long-duration purified hesperidin, particularly in individuals with metabolic disorders and obesity, had a positive effect on insulin levels. However, subsequent trial sequential analysis revealed that hesperidin confers no statistically significant improvement in HOMA-IR. In conclusion, the current body of evidence does not support hesperidin as an effective intervention for ameliorating insulin resistance or enhancing glycemic control. Future investigations are warranted to explore its potential efficacy in specific populations or subgroups. Systematic review registration:PROSPERO, identifier (CRD420251102342).

Diabetic Foot Ulcers (DFUs) represent a global healthcare challenge, imposing substantial socioeconomic burdens due to their increasing incidence and associated mortality. This study evaluates the efficacy and safety of external phytotherapy (utilizing various plant-derived compounds, including Chinese herbal medicines and plant-derived liposomes, administered topically) for the treatment of DFUs. Relevant studies were identified from major electronic databases (PUBMED, EMBASE, WOS, and the Cochrane Library) that were searched up to April 30, 2024. Randomized controlled trials (RCTs) that evaluated the effects of external phytotherapy for DFUs. The treatment group was treated with external phytotherapy plus conventional treatment, while the control group received conventional treatment alone. Two evaluators independently screened and selected literature, extracted data, and assessed the risk of bias. The outcome measures included complete ulcer healing, ulcer improvement, ulcer area reduction, and healing time. Weighted mean difference (WMD), standardized mean difference (SMD), and relative risk (RR) with 95

Radiation‑induced lung injury (RILI) remains a dose‑limiting and life‑threatening complication of thoracic radiotherapy. The present study aimed to evaluate the therapeutic efficacy and mechanism of the naturally extracted flavonoid, 5,7,8‑trimethoxyflavone (HY‑N7656), in inhibiting RILI. Lung injury in mice was evaluated using micro‑computed tomography, histopathological analysis, enzyme‑linked immunosorbent assay and western blotting. Network pharmacology was conducted to predict the potential therapeutic targets and signaling pathways of HY‑N7656 in RILI. Cell Counting Kit‑8, wound healing, immunofluorescence, reverse transcription‑quantitative (RT‑q) PCR and protein expression analyses were carried out in vitro using TGF‑β‑stimulated A549 cells to evaluate epithelial‑mesenchymal transition (EMT) and signaling activity. Results of the present study revealed that HY‑N7656 markedly alleviated pulmonary inflammation and fibrosis in irradiated mice, leading to a reduction in α‑smooth muscle actin expression. In addition, EMT was effectively reversed following treatment with HY‑N7656 in A549 alveolar epithelial cells treated with TGF‑β, accompanied by restoration of E‑cadherin expression and downregulation of mesenchymal markers, such as N‑cadherin and vimentin. Network pharmacology analysis and molecular docking validation identified the PI3K/Akt pathway as a central target, which was subsequently confirmed via western blot analysis. Moreover, results of the present study demonstrated that HY‑N7656 inhibited radiation‑induced activation of PI3K and Akt. To the best of the authors' knowledge, the present study was the first to demonstrate that HY‑N7656 modulates the PI3K/Akt signaling pathway to suppress the progression of EMT in RILI, establishing HY‑N7656 as a multi‑target inhibitor of RILI. These findings present a potential strategy to enhance the safety of radiotherapy, warranting further preclinical and clinical evaluation.

Abstract. Ferroptosis, an iron-dependent form of programmed cell death, has attracted significant attention in the field of immunometabolism. Macrophages, which are key immune cells, undergo metabolic reprogramming and polarization, influencing disease progression. This review investigates the interplay between ferroptosis signaling and macrophage glycometabolic reprogramming. To this end, it highlights the roles of iron, lipid, and amino acid metabolism in ferroptosis, alongside the distinct glycometabolic pathways in M1 and M2 macrophages. It also examines how gluconeogenesis, lactate, nicotinamide adenine dinucleotide phosphate, glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway regulate ferroptosis. Furthermore, the review investigates the feedback mechanisms between macrophage polarization and ferroptosis signaling and discusses the implications of these interactions in diseases such as cancer, metabolic disorders, infections, neurodegenerative conditions, and cardiovascular diseases. Finally, it proposes therapeutic strategies targeting ferroptosis to modulate macrophage polarization, offering new insights for disease treatment. Thus, this work provides a foundation for understanding ferroptosis–macrophage metabolism interactions and identifies potential therapeutic targets.

The sterility and controllable biological functionalities of implantable medical devices determine their lifespan, safety, and therapeutic efficacy. Inspired by the thermal effect of working electronic chips, which consist of various heterostructures, we have developed an electronic chip-mimetic sonothermal platform through constructing metal-semiconductor heterogeneous interface. Through magnetron sputtering on the surface of the sandblasted/acid-etched pretreated titanium (pTi), we find that semiconductor coatings (TiO2, Si, ZnO, and Te) endow pTi with different in situ sonothermal effects (ΔT > 18°C, 15 min) under ultrasound (US) irradiation, whereas conductor coatings do not. The sonothermal mechanism of pTi-semiconductor is associated with US-activated electron and phonon transport within the heterogeneous interface of implants, which is determined by the electrical and phonon characteristics of pTi-semiconductor, including their matching degree, thermal conductivity, defected structure, and type of semiconductor. Clinical titanium screws were introduced with defected structure in oxygen layer (TiO2-x) and bone-derived whitlockite, which shows great sonothermal/sonodynamic effects for efficient elimination of biofilm infection and improved osseointegration. In addition, the prepared NiTi-TiO2-x guidewire enables rapid thrombolysis (30 min) in the deep vein thrombosis of beagles after 10 min of sonothermal/urokinase treatment. The electronic chip-mimetic sonothermal platform provides a promising and widespread clinical application prospect.

Objective To assess the therapeutic effects of electroacupuncture (EA) in a rat model of diabetic cystopathy (DCP) and examine its impact on the expression of transient receptor potential vanilloid 1 (TRPV1) in the dorsal root ganglion (DRG). Methods Sixty male Sprague-Dawley rats were divided into four groups: control, DCP, EA, and sham EA (n = 10). DCP was induced using a high-fat diet, followed by streptozotocin injection. EA was administered at the Pangguangshu (BL 28) and Sanyinjiao (SP 6) acupoints for 8 weeks. Bladder function, structure, and molecular changes were evaluated using ultrasonography, urodynamic tests, bladder weight measurements, histological staining (hematoxylin and eosin and Masson’s trichrome staining), transmission electron microscopy, immunohistochemical analysis, and western blot for TRPV1 expression in the DRG. Results The DCP group exhibited significantly increased bladder weight, wall thickness, collagen fiber expression, maximum bladder capacity (MBC), post-void residual (PVR), and leakage point pressure, along with reduced bladder compliance (BC) and voiding efficiency (V%) compared with the Control group (all P < .05). EA treatment significantly decreased bladder weight (P = .003), collagen deposition (P = .002), wall thickness (P = .027), MBC (P = .046), and PVR (P = .023), and increased BC (P = .048) and V% (P = .022) compared with sham EA. Ultrastructural damage in DRG neurons was markedly ameliorated by EA. TRPV1 protein expression in the DRG was significantly higher in the EA group than in the sham EA group (immunohistochemistry: P = .003; western blot: P = .001). Conclusion EA alleviates bladder dysfunction and remodeling in DCP rats, an effect associated with upregulated TRPV1 expression in the DRG, reduced bladder fibrosis, and preserved neuronal ultrastructure. These findings suggest a potential role for TRPV1 signaling in mediating the therapeutic effects of EA, warranting further functional investigation.

Metabolic syndrome (MetS) is traditionally characterized by a cluster of abnormalities, including obesity, hyperglycemia, dyslipidemia, and hypertension, with clinical management historically centered on the stabilization of these individual parameters. However, the chronic, progressive nature of MetS and the persistent challenge of fully reversing its clinical manifestations indicate that its underlying pathophysiological mechanisms extend far beyond the mere summation of individual risk factors. Recent evidence reveals that the core pathogenesis of MetS involves a complex interplay between "metabolic memory" and "inflammatory memory." Metabolic memory represents the long-term imprint sustained at the cellular level from historical metabolic disturbances, mediated via epigenetic reprograming and mitochondrial dysfunction. Concurrently, inflammatory memory reflects the immune system's "trained immunity" (TI) under metabolic stress, which primes immune cells to maintain a persistent state of low-grade, chronic pro-inflammation. These two pathological processes interact closely through signaling cascades-such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK-STAT), and Toll-like receptors (TLRs) pathways-thereby translating metabolic danger signals into chronic inflammation and the maladaptive regulation of lipid metabolism, insulin signaling, and vascular function. This cascade amplification mechanism, propagating from localized cellular memory to systemic inflammation, drives progressive end-organ damage in the heart, liver, kidneys, and vasculature, establishing the unifying pathological foundation of MetS and its associated complications. Consequently, clinical intervention strategies for MetS must transition from the superficial management of biochemical indicators toward therapies that specifically target and reverse this deeply ingrained metabolic-inflammatory memory. This review systematically constructs a comprehensive theoretical framework for metabolic-inflammatory memory in MetS and evaluates its clinical translational value, aiming to provide a mechanistic foundation for the development of targeted, curative clinical interventions.

Migraine affects over one billion people worldwide, yet preventive options remain limited. Here, we provide convergent pharmacoepidemiological and mechanistic evidence that GLP-1 receptor agonist (GLP-1 RA) use is inversely associated with migraine. Analysing 16,998,128 deduplicated reports from the US FDA Adverse Event Reporting System (FAERS, 2004–2024), we found GLP-1 RA class use was inversely associated with migraine reporting (reporting odds ratio 0.759, 95% CI 0.720–0.801; E-value 1.96). Five of seven individual agents showed significant inverse associations, and all 18 prespecified subgroup analyses survived false discovery rate correction. Restrictive comparator analyses against SGLT2 inhibitors, DPP-4 inhibitors, and metformin confirmed a GLP-1 RA-specific signal. Independent analysis in the Japanese JADER database corroborated the inverse association for headache (ROR 0.226, 0.085–0.602). Network pharmacology and molecular docking identified favourable binding to migraine-relevant targets NOS3 and CALCRL. These findings provide a rationale for randomised trials evaluating GLP-1 RAs as migraine-preventive agents.

Abstract Background Elevated resting heart rate (RHR) predicts mortality in older adults, primarily through cardiovascular disease (CVD). Prior cohort evidence suggests that RHR also predicts mortality in younger adults, but whether this association operates through cardiovascular or non-cardiovascular pathways has not been directly tested. Methods and Results We analyzed 3291 adults aged 20 to 49 years from NHANES 1999–2004 linked to mortality data through 2019 (median follow-up, 17.8 years; 120 deaths). RHR and heart rate reserve (HRR) were modeled per 10-bpm increment using Cox regression adjusted for demographic, lifestyle, and comorbidity covariates. Each 10-bpm RHR increase was associated with higher all-cause mortality (hazard ratio [HR], 1.26; 95% CI, 1.07–1.50; P=.007), driven by non-CVD mortality (HR, 1.28; 95% CI, 1.07–1.55; P=.009) rather than CVD mortality (HR, 1.15; 95% CI, 0.77–1.71; P=.51). A behavioral/external composite (accidents and NCHS residual causes, including suicide and liver disease) reached significance (HR, 1.35; P=.02), whereas a disease-oriented composite did not (P=.20). The association was absent before age 35 (HR, 0.98; P=.88) but pronounced at ages 35–39 (HR, 2.60; P=.001). HRR was not associated with any outcome. Conclusions In young US adults, elevated RHR predicted mortality through non-cardiovascular rather than cardiovascular pathways, concentrated among behavioral and external causes. The association emerged at age 35, below current screening thresholds. HRR under submaximal conditions carried no prognostic value. RHR in young adults may reflect global health vulnerability rather than cardiovascular risk alone. Clinical Perspective What Is New? In adults aged 20 to 49 years, elevated resting heart rate predicted all-cause mortality through non-cardiovascular pathways, particularly behavioral and external causes of death, rather than cardiovascular disease. The resting heart rate–mortality association was absent before age 35 and emerged sharply thereafter, suggesting a risk window below the starting age of SCORE2 and the Pooled Cohort Equations. Heart rate reserve measured under submaximal exercise conditions showed no prognostic value across all outcomes and subgroups. What Are the Clinical Implications? Clinicians encountering persistently elevated resting heart rate in young adults may consider evaluating for autonomic-mediated risk factors (psychological distress, substance use, sleep disorders, chronic inflammation) rather than focusing exclusively on cardiovascular workup. Adults aged 35 to 49 years with elevated resting heart rate may benefit from enhanced screening not currently captured by standard cardiovascular risk assessment tools. Population-based surveys and primary care settings using submaximal exercise protocols should interpret heart rate reserve results with caution, as submaximal protocols may lack the physiological stress needed to unmask prognostically meaningful chronotropic impairment.

Ischemic stroke is a fatal cerebrovascular disease, and reperfusion, the primary approach for restoring blood supply, can lead to significant oxidative stress and subsequent damage to the cerebrovascular system. Developing strong antioxidant agents could be a solution, but it remains a Herculean challenge. Herein, inspired by the three-dimensional coordination structures and active center of natural Mn-superoxide dismutase, coupled with the synergistic monoatom/cluster sites found in antioxidases, we propose the de novo design of Mn-organic complex-supported Ru clusters (MnCP-Ru) to function as an artificial metalloenzyme for cascade elimination of reactive oxygen species (ROS), aimed at protecting against cerebral ischemic-reperfusion injury. Our studies show that Mn-organic ligands increase the electron density of Ru clusters, thereby improving their binding to oxygen species and resulting in effective, cascade-like antioxidase activities. Accordingly, the MnCP-Ru can reduce the number of apoptotic neurons by attenuating ROS-induced cell damage and exert powerful anti-inflammatory effects by inhibiting lipid peroxidation, microglial and astrocyte activation in brain tissues, thus leading to powerful protection and repair of cerebral ischemia-reperfusion injury. We believe the MnCP-Ru biocatalyst, with its synergistic sites and cascade ROS elimination, offers effective antioxidative performance, paving the way for developing materials to treat ischemic-reperfusion injury and other oxidative stress-related diseases.

Type 2 diabetes mellitus(T2DM) is a major metabolic disease with high prevalence in China, and its multisystem complications involving the heart, brain, kidneys, and eyes pose a serious threat to public health. According to 2023 data from the International Diabetes Federation(IDF), the prevalence of diabetes among Chinese adults has reached 12.4%, with approximately 140 million patients, over 90% of whom have T2DM. Although western hypoglycemic therapies can effectively control blood glucose, they remain limited in improving insulin resistance, regulating constitution, and preventing and treating complications. In TCM, T2DM falls under &quot;spleen heat&quot; and &quot;consumptive thirst&quot;, with core pathogenesis characterized by disordered body fluid metabolism and imbalance of Qi, blood, Yin, and Yang, primarily affecting the liver, spleen(stomach), and kidneys. Based on the evolutionary pattern of pathogenesis, this study proposes six syndrome classifications, i.e., Yuke(depression-thirst), Reke(heat-thirst), Shike(dampness-thirst), Tanke(phlegm-thirst), Yuke(stasis-thirst), and Xuke(deficiency-thirst). Yuke(depression-thirst) presents with chest and hypochondriac distension and elevated blood glucose during emotional fluctuations. Reke features the typical &quot;three excesses and one loss&quot; with Yangming exuberant heat. Shike centers on dry mouth without desire to drink, obesity, and greasy tongue coating. Tanke exhibits dizziness, chest oppression, and excessive phlegm on the basis of Shike. Yuke(stasis-thirst) is marked by dark-purplish tongue and fixed pain. Xuke is differentiated according to the degree of Qi, Yin, Yang, or essence deficiency. Classical formulas are applied correspondingly as follows: Dachaihu Decoction for Yuke(depression-thirst), Baihu Jia Renshen Decoction for Reke, Gegen Qinlian Decoction and Wuling Powder for Shike, Banxia Xiexin Decoction for Tanke, Guizhi Fuling Pills for Yuke(stasis-thirst), and Jingui Shenqi Pills, Shengmai Powder, or Zuogui Pills for Xuke, with flexible combinations for comorbid conditions. Following the integrated TCM-western medicine approach of aligning formula with syndrome and combining pathogenesis, pathology, drug properties, and pharmacology, this study emphasizes pathogenesis-centered application of classical formulas integrated with modern pharmacology to construct a &quot;syndrome differentiation-disease differentiation-target differentiation&quot; trinity treatment model, providing a new TCM strategy for precise prevention and treatment of T2DM and its complications, especially in intervening in insulin resistance and regulating intestinal flora.

Purpose:To evaluate the potential clinical effect of Yanghe decoction on diabetic foot. Methods:We comprehensively searched Web of Science, PubMed, The Cochrane Library, Embase, CNKI, Wanfang, and VIP databases from their inception to December 6, 2025, to identify randomized controlled trials (RCTs) investigating Yanghe decoction for DF. Meta-analysis was performed using RevMan 5.4 and Stata 15.0 software. Results:A total of 15 studies with 1224 patients were included, 614 in the treatment group and 610 in the control group. The results suggest that the total effective rate of the treatment group may be higher than that of the control group (RR = 1.23, 95% CI: 1.17 to 1.29, p < 0.00001). The wound healing time of the treatment group may be shorter than that of the control group (MD = -9.36, 95% CI: -14.21 to -4.50, p = 0.0002), and the treatment group may have potential advantages over the control group in the improvement of wound area after treatment (SMD = -2.57, 95%CI: -3.94 to -1.20, p = 0.0002). There was no statistically significant difference in the ankle-brachial index (ABI) between the treatment group and the control group (MD = 0.05, 95% CI: -0.09 to 0.18, p = 0.51). The funnel plot of the total effective rate between the treatment group and the control group suggested that there was a publication bias in the effective rate. Further analysis of the results by the nonparametric trim and filling method suggested that the results of the meta-analysis were relatively stable, and the possible publication bias did not substantially affect the results. Conclusions:Low certainty evidence suggests that Yanghe decoction may potentially improve the clinical symptoms of diabetic foot, may shorten the wound healing time, and may reduce the wound area. However, the independent clinical efficacy of Yanghe decoction for diabetic foot cannot be determined due to the high heterogeneity of cointerventions in the included studies. This study is further limited by the insufficient quantity and quality of the included studies, and the above tentative implications need to be verified by more large-sample and multicenter RCT studies that standardize interventions and control for cointervention variables.

1,5-anhydroglucitol (1,5-AG) is sensitive and rapid to glycemic fluctuations. It is important for short-term glycemic monitoring, as it can reflect the glycemic fluctuations within the last 1-2 weeks, as well as postprandial hyperglycemia. Numerous studies have demonstrated that 1,5-AG is associated with diabetic nephropathy, diabetic retinopathy, diabetic cardiovascular diseases, diabetic cerebrovascular diseases, diabetic neurodegeneration, and diabetic pregnancy complications. Therefore, 1,5-AG has potential application value in the risk stratification of diabetes complications and can serve as a complementary biomarker for the risk assessment of diabetes complications. Salivary 1,5-AG, as a non-invasive indicator for glycemic monitoring, is well accepted by patients with remarkable advantages in compliance and shows promising clinical application prospects. However, the relevant detection methods still need to be optimized and improved. This review summarizes the basic characteristics of 1,5-AG and systematically elaborates its clinical application value and research status in diabetes complications, aiming to provide a reference for the rational clinical application and future research of 1,5-AG.

BACKGROUND:Metabolic dysregulation plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). While the metabolic vulnerability index (MVX) captures multidimensional metabolic characteristics, its utility as a composite score and its specific association with incident T2DM risk and diabetes-related mortality outcomes require further validation in large-scale populations. METHODS:This study harnessed data from the UK Biobank (UKB), comprising a cohort of over 500 000 native UK residents recruited between 2006 and 2010. We conducted two independent analyses: incident T2DM in the general population and all-cause mortality in the baseline diabetes cohort. After excluding individuals with baseline diabetes and those missing MVX information, the analysis of incident T2DM included 453 209 participants; while the all-cause mortality analysis among diabetes cohort included 34 735 diabetic patients after excluding those with missing MVX information. Cox proportional hazards models were employed to evaluate the associations between MVX and outcomes. Subgroup analyses were performed by gender, age and BMI, and sensitivity analyses were conducted to assess the robustness of the findings. RESULTS:Each 1-standard deviation (SD) increase in MVX was associated with a 14% increased risk of incident T2DM (HR = 1.14, 95% CI: 1.11-1.16, p < 0.001). Participants in the highest quartile (Q4) showed a 32% higher risk compared to the lowest quartile (Q1) (HR = 1.32, 95% CI: 1.24-1.39, p = 0.004). Subgroup analyses indicated that the association was more pronounced in individuals with normal BMI, females, and those aged < 60 years. Specifically, each 1-SD increase in MVX was associated with a 24% increased risk of incident T2DM in the normal BMI group (HR = 1.24, 95% CI: 1.16-1.32, p < 0.001), a 17% increased risk in females (HR = 1.17, 95% CI: 1.14-1.20, p < 0.001) and an 18% increased risk in participants aged < 60 years (HR = 1.18, 95% CI: 1.14-1.22, p < 0.001). Regarding mortality, each 1-SD increase in MVX was associated with a 10% higher risk of all-cause mortality among participants with diabetes (HR = 1.10, 95% CI: 1.07-1.13, p < 0.001) and a 16% higher risk of cardiovascular disease (CVD) mortality (HR = 1.16, 95% CI: 1.06-1.26, p < 0.001). Moreover, subgroup analysis revealed an 18% increased risk of all-cause mortality in individuals with T1DM (HR = 1.18, 95% CI: 1.07-1.30, p < 0.001) and a 7% increased risk in those with T2DM (HR = 1.07, 95% CI: 1.04-1.10, p < 0.001). Sensitivity analyses corroborated the robustness of the associations between MVX and incident T2DM, as well as all-cause mortality in patients with diabetes. CONCLUSIONS:This study highlights the independent association between MVX and T2DM outcomes as well as diabetes-related mortality. The strength of MVX lies in capturing the risk of incident T2DM in individuals with normal BMI, younger populations and females, thereby serving as a valuable supplementary tool for clinical early screening and the identification of high-risk individuals missed by traditional indicators.

BackgroundSepsis is a severe systemic inflammatory response syndrome, and effective metabolic signatures for predicting its risk are currently lacking. This study seeks to evaluate the associations between inflammatory vulnerability (IVX), metabolic malnutrition (MMX), and metabolic vulnerability (MVX) and the risk of sepsis.MethodsWe conducted a prospective cohort study using data from the United Kingdom Biobank. Cox proportional hazards models were utilized to examine the association between these composite indices and sepsis risk, while restricted cubic spline (RCS) analysis was applied to identify potential nonlinear trends. Subgroup analyses based on medical history, lifestyle factors, and demographic characteristics were performed in fully adjusted models. Sensitivity analyses employed 3-year left truncation and adjusted for CRP and glycated hemoglobin, as well as excluding participants with baseline comorbidities.ResultsIn fully adjusted models, a 1-SD increase in MVX corresponded to an 18% higher sepsis risk (HR: 1.18; 95% CI, 1.15–1.20; p < 0.01), whereas the highest quartile (Q4) showed a 43% increased risk versus Q1 (HR: 1.43; 95% CI, 1.35–1.52; p < 0.01). Positive associations were also observed for IVX (HR per SD: 1.15; 95% CI, 1.13–1.18; p < 0.01) and MMX (HR per SD: 1.10; 95% CI, 1.07–1.12; p < 0.01). Subgroup demonstrated that MVX was consistently linked to sepsis across various subgroups, with a stronger association than IVX or MMX. Notably, in participants with normal BMI, females, and those with severely decreased eGFR, the risk increased by 23% (HR: 1.23), 26% (HR: 1.26), and 28% (HR: 1.28) per SD increase in MVX, respectively (all p < 0.01). RCS analysis confirmed nonlinear dose–response relationships (nonlinear p = 0.018), with an inflection point of 38 for MVX; beyond this threshold, sepsis risk increased sharply. Sensitivity analyses supported the aforementioned results.ConclusionMVX, IVX, and MMX all demonstrated positive correlations with sepsis risk characterized by distinct nonlinear patterns. The composite index MVX, integrating inflammation and metabolic factors, was slightly more strongly associated with sepsis compared to IVX or MMX.