Previous studies have indicated that elevated selenium levels curb systemic lupus erythematosus (SLE) risk, whereas the specific mechanisms remain to be elucidated. Thereby, our study is conducted to explore the mediating function of proteome on the association between selenium and SLE. Summary data for plasma proteins came from six large-scale genome wide association studies (GWASs). The data of selenium were derived from a GWAS meta-analysis involving 9639 individuals, and those with SLE were obtained from SLE meta-GWASs (5206 cases and 9066 controls). Two-sample Mendelian randomization (MR) was performed using inverse-variance weighting (IVW), followed by a series of sensitivity analyses to examine the causal relationship between plasma proteins and SLE. Additionally, a two-step MR (TSMR) analysis was applied to explore the mediating role of plasma proteins in the link between selenium and SLE. Moreover, multivariable MR (MVMR) was utilized to adjust and calculate the mediating effect, revealing the potential mechanisms underlying the impact of selenium on SLE. In the MR analysis, we found 24 plasma proteins associated with SLE among 4372 unique plasma proteins. Notably, three plasma proteins exhibited a causal link with selenium. Through mediation analysis, we identified sex hormone–binding globulin (SHBG) mediated the causal effect between selenium and SLE. Specifically, increased selenium levels could lower SLE risk by reducing SHBG levels, with a mediation proportion of 22

Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, often resulting in heart failure due to adverse cardiac remodeling triggered by inflammation and fibrosis. Traditional Chinese Medicine (TCM), particularly compounds like Quercetin from Licorice and Peony, has shown promise in modulating inflammation and oxidative stress in cardiovascular diseases. This study integrates bioinformatics and experimental validation to explore the therapeutic potential of Quercetin in MI. Using Mendelian Randomization (MR) and colocalization analysis, we identified key MI-related genes, such as VEGFA, PTK2, and GGT1, whose expression is influenced by Quercetin. Bioinformatics tools predicted these genes as targets of Quercetin, with molecular docking revealing stable interactions between the compound and these genes. Single-cell RNA-sequencing of MI samples confirmed the expression of these genes in cardiac muscle cells (CMs) and macrophages, highlighting their role in tissue repair and inflammation. In experimental models, Quercetin treatment significantly altered the expression of these genes, enhancing myocardial cell recovery and reducing infarct size. This study provides molecular insights into how Quercetin and other TCM compounds could modulate critical pathways involved in MI recovery, supporting their potential as adjunct therapies. The findings bridge traditional medicine with modern bioinformatics, opening new avenues for therapeutic strategies to improve cardiac function and patient outcomes in MI.

Background:Atherosclerosis (AS) is a chronic inflammatory disorder driven by dysregulated lipid metabolism and remains a leading cause of cardiovascular morbidity. The Shen-Hong-Tong-Luo (SHTL) preparation has demonstrated clinical benefit in stabilizing atherosclerotic plaques, yet its molecular mechanisms are not fully defined. Purpose:This research sought to elucidate the protective effects exerted by SHTL on AS progression. Methods:To investigate the impact of SHTL on macrophage function and plaque stability, we utilized ApoE-/- mice models and bone marrow-derived macrophages (BMDMs) stimulated with lipopolysaccharide (LPS) and oxidized low-density lipoprotein (Ox-LDL). Network pharmacological analysis was conducted to predict potential therapeutic targets of SHTL, with a particular focus on the efferocytosis pathway. These predictions were subsequently confirmed by immunofluorescence (IF) staining and flow cytometry experiments performed on ApoE-/- mice and BMDMs. Furthermore, using data-independent acquisition (DIA) proteomics, milk fat globule-epidermal growth factor 8 (Mfge8) was identified as a critical factor facilitating SHTL-enhanced efferocytosis. Chip-PCR and GW9662 were applied to explore the involvement of peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Results:SHTL markedly attenuated the progression of AS, demonstrated by reduced plaque formation within both the aortic root and aorta, diminished plasma lipid concentrations, and suppressed inflammatory responses. In vitro assays using BMDMs revealed that SHTL significantly inhibited foam cell formation and inflammation induced by Ox-LDL and LPS. Furthermore, SHTL enhanced efferocytosis both in vivo and in vitro by upregulating Mfge8 expression. Treatment with GW9662 abolished these beneficial effects, confirming that SHTL exerts its protective actions via activation of the PPARγ/Mfge8 pathway. Conclusion:SHTL demonstrates significant anti-inflammatory and lipid-regulatory effects, attenuating AS progression through the PPARγ/Mfge8 pathway, thereby enhancing macrophage efferocytosis. These findings highlight a novel mechanism by which SHTL may contribute to preventing and treating atherosclerotic diseases.

Carotenoids are common natural anti-inflammatory antioxidants produced by plants and some microorganisms. However, there are limited reports on the association between carotenoids and risk of rheumatoid arthritis (RA). We analyzed data of participants from the National Health and Nutrition Examination Survey (NHANES) and UK Biobank (UKB). In the NHANES, a total of 40,410 and 13,440 participants were included to evaluate the association of dietary carotenoid intake and serum carotenoid levels with RA, respectively. Among 179,171 participants in the UKB, 2,156 individuals developed RA over a median follow-up of 7.74 years. A weighted multivariable logistic regression model and quantile G-Computation (QGC) model were established to investigate single and joint effect of carotenoid levels (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin) on RA in NHANES by cross-sectional study design. Furthermore, Cox proportional hazards regression model was used to validate the potential association in UKB cohort, and restricted cubic spline (RCS) regression was applied to estimate the possible nonlinear association. Compared to the lowest quartile (Q1), dietary intake level of alpha-carotene in Q3 were consistently associated with a decreased risk of RA in NHANES (odds ratio [OR]: 0.771, 95

Chronic diabetic wounds are difficult to treat because persistent oxidative stress, mitochondrial dysfunction, and impaired stromal-vascular communication jointly delay tissue repair. In this study, we developed a bioinspired hyaluronic acid-catechol-PEG-amine (HA-CPA) hydrogel through dynamic Schiff-base crosslinking for topical diabetic wound management. The HA-CPA hydrogel formed a porous, self-supporting network and showed favorable cytocompatibility and hemocompatibility. Owing to catechol-containing moieties, the hydrogel displayed strong antioxidant activity, with more than 80% radical-scavenging efficiency in DPPH and ABTS assays. Under diabetic-mimicking conditions, HA-CPA hydrogel extracts reduced intracellular reactive oxygen species, helped preserve mitochondrial membrane potential, and improved fibroblast migration and endothelial angiogenic behavior, including tube formation. In a streptozotocin-induced diabetic full-thickness wound model, HA-CPA treatment accelerated wound closure, enhanced collagen deposition, and promoted re-epithelialization without detectable systemic toxicity in major organs. These findings indicate that HA-CPA hydrogel provides a practical wound-dressing platform that combines redox regulation, inflammatory microenvironment modulation, cellular protection, and vascular-supportive activity.

In current trials of acupuncture for migraine treatment, the heterogeneity in therapeutic outcomes has been noted, which may be closely tied to the use of diverse sham acupuncture designs. This paper aims to evaluate the reporting quality of sham acupuncture and assess the potential impact of the consistency for intervention procedure between sham and true acupuncture groups on efficacy size in randomized controlled trials (RCTs) for migraine. RCTs with sham acupuncture as a control in migraine were searched in four English and four Chinese databases from inception to May 2024. Based on the SHARE checklist, the distribution of reported items and reporting rates were investigated. The meta-regressions were conducted to assess the potential impact of the consistency of intervention procedures between sham and true acupuncture groups on efficacy size of acupuncture for migraine. Evaluation of the 46 included studies revealed that a significant proportion of item descriptions were incomplete, such as the information informed or explained to patients (Item 5, 4(8.70

BACKGROUND:. Despite advances in reperfusion therapy, the incidence and mortality risk of heart failure (HF) remain high among patients with acute myocardial infarction (AMI). Naoxintong (NXT), a well-characterized polyherbal formulation derived from traditional Chinese medicine, has shown potential benefits in preclinical and small-scale clinical studies, but its efficacy has not been tested in a large-scale randomized controlled trial. AIM:. To rigorously evaluate the efficacy and safety of NXT in reducing HF and major adverse cardiovascular events (MACEs) among AMI patients after reperfusion therapy. STUDY DESIGN:. A prospective, multicenter, randomized, double-blind, placebo-controlled, superiority trial. METHODS:. Eligible post-reperfusion AMI patients from 21 hospitals in China were randomly assigned to receive either NXT (4 capsules, three times daily) or a matching placebo for 3 months, in addition to guideline-directed medical therapy (GDMT), with follow-up through 12 months. The primary endpoint was the incidence of new-onset HF within 12 months after randomization. Participants, clinicians, and outcome assessors were blinded to treatment allocation throughout the study period. RESULTS:. A total of 379 patients were included in the primary analysis (mean age 61.6 years; 78.1% male). The incidence of HF was significantly lower in the NXT group than in the placebo group (5.98%vs. 14.06%; HR 0.41, 95% CI 0.21-0.81; p = 0.01). The incidence of MACEs was also reduced with NXT (7.97%vs. 14.84%; HR 0.52, 95% CI 0.28-0.98; p = 0.04). The rates of serious adverse events (7.97%vs. 14.84%; p = 0.042) and any adverse events (7.97%vs. 21.09%; p < 0.001) were lower in the NXT group. No other significant between-group differences were observed for secondary outcomes or adverse event subtypes. CONCLUSION:. NXT, administered in addition to standard GDMT, significantly reduced the 12-month risk of HF and MACEs in reperfused AMI patients, with a favourable safety profile. These findings support NXT as a promising complementary strategy for secondary prevention after AMI.

OBJECTIVE:To investigate the effect of Buzhong Yiqi decoction (BZYQ) and its potential mechanism by conducting a comprehensive analysis of intestinal microbiota and metabolomics in autoimmune thyroiditis (AIT) rats. METHODS:An AIT model with antibiotic cocktail were established. After 8 weeks of intervention with BZYQ, the levels of anti-thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TGAb) were measured. Pathological changes were assessed using hematoxylin and eosin staining. Changes of gut microbiota and fecal metabolites were analyzed through 16S RNA sequencing and metabolomics analysis. RESULTS:BZYQ intervention improved pathological damage of thyroid gland in AIT rats and significantly reduced the levels of anti-thyroid antibodies. Additionally, it had an ameliorative effect on the pathological damage of the colon. Also, BZYQ increased the abundance of Lactobacillus reuteri, reversing the dysbiosis of the gut microbiota. And BZYQ could regulate tryptophan metabolism of tryptophan to reverse metabolic disorders in HT. The correlation analysis indicated a close relationship between tryptophan metabolism and Lactobacillus reuteri. CONCLUSIONS:BZYQ is a promising therapeutic approach for HT. Its mechanism in treating HT may be associated with the regulation of gut microbiota dysbiosis and the improvement of gut-derived metabolic disorders.

ETHNOPHARMACOLOGICAL RELEVANCE:The herb pair of Acori Tatarinowii Rhizoma (Shi Chang Pu) and Polygalae Radix (Yuan Zhi) is a classic combination in Traditional Chinese Medicine for "opening the orifices to revive the mind, and relieving depression to calm the spirit". Acori Tatarinowii Rhizoma-Polygalae Radix Herb Pair (APHP) has been widely used in treating post-stroke depression (PSD) and has shown promising results. However, its underlying combined mechanism of action remains unclear. AIM OF THE STUDY:This study is aimed to evaluate the therapeutic effect of APHP on PSD and elucidate its mechanism through transcriptome and metabolomic approaches. MATERIALS AND METHODS:A PSD rat model was developed using middle cerebral artery occlusion (MCAO) coupled with chronic unpredictable mild stress (CUMS). Subsequently, the therapeutic efficacy of APHP on PSD were assessed through behavioral experiments, hematoxylin-eosin (HE) staining, Nissl staining, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Then a systematic study was conducted on its mechanism using network pharmacology, transcriptomics and metabolomics. RESULTS:APHP effectively alleviated depressive-like behaviors and restrained neuroinflammation in PSD rats. Specifically, APHP reversed anhedonia and despair-like states, ameliorated pathological brain damage and neuronal loss, inhibited inflammation, and regulated neurotransmitter levels. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis and network pharmacology indicated that kaempferol and α-Asarone might be the effective candidate ingredients ameliorating PSD via the modulation of inflammatory signaling pathways. Transcriptomic analysis revealed that compared to the model group, there were 80 genes upregulated and 167 genes downregulated in the APHP group. Metabolomic analysis identified upregulation of theobromine and 3-methylxanthine in the model group, which were downregulated following APHP treatment. Further analyses suggested that APHP may regulate the inflammatory response via the PI3K/AKT/NF-κB signaling pathway, inhibit the gene expression of CCL4 and IL-1 β in brain tissue, ameliorate metabolic disorders, and modulate the caffeine metabolism pathway, thereby exerting a protective effect. CONCLUSIONS:APHP exhibited significant anti-PSD effects, potentially improving depressive symptoms and alleviating neuroinflammation by regulating the PI3K/AKT/NF-κB signaling cascade and modulating the caffeine metabolism pathway. This research establishes a solid basis for the clinical use of APHP in PSD management and paves the way for developing safer and more effective drugs derived from this herb pair.

Chemotherapy, a standard treatment for breast cancer (BC), is known to exert neurotoxic effects on the central nervous system. The aim of this study was to identify consistent patterns of brain structural and functional alterations linked to chemotherapy in patients with BC and explore potential clinical correlates, such as age, education, and treatment characteristics. Data from 29 neuroimaging investigations, including structural magnetic resonance imaging (MRI), diffusion tensor imaging, and resting-state functional MRI, were analyzed using a coordinate-based meta-analysis. The results revealed significant gray matter reductions in regions including the orbitofrontal cortex, anterior cingulate cortex, insula, cerebellum, and rolandic operculum, alongside functional hypoactivation in the rolandic operculum and insula, when comparing chemotherapy-treated patients to chemotherapy-naive controls. These findings suggest that chemotherapy primarily affects regions involved in cognitive and emotional regulation. A higher education level may serve as a protective factor, possibly reflecting greater gray matter structural integrity, that mitigates chemotherapy-related neurotoxic effects. This study may offer insights into the underlying neural mechanisms of chemotherapy-related cognitive changes. Further research should investigate treatment-specific effects and long-term outcomes.

ObjectiveParkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterized by worsening motor symptoms, that significantly impair patients’ activities of daily living and quality of life. Emerging evidence indicates a correlation between body mass index (BMI) and PD progression and prognosis. However, few systematic bibliometric analysis has been conducted in this research field. This study aims to comprehensively investigate the clinical translation potential and research hotspots of BMI management in PD pathogenesis, treatment, and care through bibliometric approaches.MethodsPublications related to BMI and PD research from 2010 to 2024 were retrieved from the Web of Science Core Collection. Bibliometric analysis was performed using “VOSviewer” “CiteSpace” and the R package “bibliometrix.”ResultsA total of 588 publications from 267 journals were analyzed. Parkinsonism and Related Disorders ranked as the most productive journal with 33 publications. Analysis of regional research contributions indicates that the United States, China, and Italy demonstrate predominant scientific influence in this discipline. Among 3,707 contributing authors, Barichella M emerged as the most co-cited author, with research spanning PD-BMI correlation, nutritional management, and gut microbiota. Keyword cluster analysis (e.g., “weight gain” “weight loss” “body mass index” “nutritional management”) highlighted metabolic alterations and nutritional interventions as research focal points, underscoring the role of BMI fluctuations in PD progression.ConclusionThis study presents the first systematic bibliometric summary of clinical translation research on BMI modulation in PD management. The findings enhance understanding of BMI’s critical role in PD research, provide theoretical foundations for BMI-based interventions to delay disease progression and reduce mortality, and identify novel research directions to advance PD treatment toward a multidisciplinary collaborative model.

Introduction/Objective: The incidence of metabolic-associated fatty liver disease (MAFLD) increases annually. Modified Zexie Decoction (MZXD) can treat this disease; however, their mechanisms of action are uncertain. This study evaluated the mechanisms of MZXD against MAFLD based on network pharmacology, molecular docking, and in vivo experiments. Methods: The main active compounds, targets and signaling pathways of MZXD against MAFLD were obtained using network pharmacological analysis. Underlying mechanisms were validated by molecular docking and in vivo assays. Results: Forty-one active ingredients and 197 intersection targets were identified. The main active ingredients include quercetin, luteolin, isorhamnetin, 3-methylhexane, and 3β- acetoxyatractylone. The main targets were TP53, JUN, HSP90AA1, MAPK1, MAPK3, AKT1, NF-κB p65, TNF, ESR1, FOS, and IL-6. The pathway enrichment analysis indicated that MZXD was related to the IL-17, TNF, and PI3K-AKT signaling pathways. Molecular docking suggested that these active ingredients bound strongly to TNF, IL-6, and NF-κB p65, which are integral components of the TNF pathway. In the rat MAFLD model, MZXD attenuated high-fat diet( HFD)-induced liver injury and lipid accumulation, decreased the serum levels of the inflammatory mediators TNF-α, IL6, and IL-1β, and inhibited the protein expression of TNF-α, IL6, p- IKB-α and p-NF-κB p65. Furthermore, immunohistochemistry results showed that MZXD attenuated the F4/80 staining intensity of the liver compared with the model group. Conclusion: Collectively, our results suggested that MZXD could improve MAFLD by downregulating TNF/NF-κB signaling mediated macrophage activation.

Evidence linking the dietary inflammatory index (DII) to health outcomes remains inconsistent and limited. This study assessed the associations between DII and 845 health outcomes (N = 78,390 to 207,832), identifying 133 outcomes significantly associated with DII after multiple comparison correction (PFDR < 0.05). Most of these health outcomes pertained to the digestive, circulatory, and endocrine/metabolic systems. Using the genetic instrument rs7910002, significantly associated with DII at the genome-wide level (P < 5 × 10−8), Mendelian randomization (MR) phenome-wide association analysis (N = 121,978 to 315,586) revealed significant associations between DII and 25 health outcomes (PFDR < 0.05). Consistent effects of DII on seven health outcomes were observed in the above analyses. Subsequently, two-sample MR analysis confirmed that higher DII increased the risk of abdominal hernia, cholelithiasis, and back pain. Our study comprehensively assessed the health effects of DII and highlighted the importance of anti-inflammatory diets for disease prevention.

Studies have shown that the colonisation of active microorganisms is more conducive to the development of tumour immunotherapy, but intuitive evidence regarding shaping of the tumour immune microenvironment is lacking. In this study, we used Bifidobacterium longum subsp. longum (XZ01) to intervene in a colon cancer mouse model and found that its mechanism may be related to the interaction between the spatial distribution of microorganisms and tumour immunity. Through the visualisation method we established, for the first time, we showed that harmful active bacteria such as Streptococcus and Rhodococcus specifically accumulate in the middle and upper layers of tumour tissue. These bacteria likely participate in signalling pathways that affect macrophages by directly contacting or invading the macrophages, leading to a nondifferentiated state in macrophages and the loss of some immune functions. Furthermore, the accumulation of Streptococcus and Rhodococcus fragments in the deep layer of tumour tissue likely upregulates the expression of IL-10 in tumour tissue and inhibits other immune cells, such as CD8+ T cells, DC and NK cells. In contrast, XZ01 can specifically compete for the growth sites of Streptococcus and Rhodococcus in the middle and upper layers of tumour tissue and probably protects macrophages from being invaded by harmful bacteria. XZ01 directly regulates the polarisation of M0 macrophages towards the M1 phenotype by upregulating IFN-gamma, thus activating tumour immunity to inhibit the growth of tumour cells. This study revealed that the influence of active microorganisms on the tumour immune microenvironment is crucial for effective immunotherapy intervention, potentially offering new targets for improving patient prognosis.

IntroductionSalvia miltiorrhiza radix et rhizoma (Danshen) is a crucial medicinal material for treating cardiovascular and cerebrovascular diseases. However, the presence of adulterants and intraspecific variability poses challenges to its clinical safety.MethodsThis study collected samples of S. miltiorrhiza from various regions and commonly encountered adulterants. The composition differences of S. miltiorrhiza radix and its adulterants were analyzed by fingerprint and broad-target metabolomics. Chloroplast genome was used to distinguish intra-genus species and DNA barcoding was used to identify germplasm sources.ResultsThe fingerprinting analysis proved that there is no chemical composition consistency between S. miltiorrhiza radix and its adulterants. Broad-targeted metabolomics can distinguish S. miltiorrhiza radix from Salvia yunnanensis radix, Dipsacus asperoides radix, and Arctium lappa radix. Additionally, comparative chloroplast genome analysis indicated that atpF and rps4-trnT-UGU were the potential DNA barcodes for S. miltiorrhiza. 259 samples from 13 provinces and 21 origins were amplified and sequenced, resulting in the identification of 62 haplotypes. The unique haplotypes found in Shanxi Luoyang, Shandong Qingdao and other places can be used as molecular geographic markers for the identification of the germplasm source of S. miltiorrhiza.DiscussionThis study systematically differentiates S. miltiorrhiza from its adulterants and highlights the potential of unique haplotypes as markers for sourcing. The findings provide strong scientific evidence for the clinical safety of S. miltiorrhiza, emphasizing the importance of proper cultivation, selection, and breeding of varieties.

Background: Ischemic stroke (IS) is a significant cause of global mortality and disability. Yiqi Huoxue Jieyu granules (YHJGs) show therapeutic potential for IS, but their mechanisms remain unclear. This study investigated YHJGs’ effects through network pharmacology, molecular docking, and experimental validation. Methods: Active YHJG components and IS targets were identified from TCMSP, GeneCards, and DisGeNET databases. Network analysis and molecular docking (AutoDock Vina) were performed. In vivo studies used 72 male Sprague-Dawley rats (MCAO model) divided into sham, model, nimodipine (10.8 mg/kg), and three YHJG dose groups (0.72, 1.44, 2.88 g/kg). Assessments included neurological scores, TTC staining, histopathology, and molecular analyses (qPCR/Western blot). Results: Network analysis identified 256 shared targets between YHJG and IS, with PI3K-AKT and MAPK as key pathways. Molecular docking showed strong binding between YHJG compounds (e.g., quercetin) and core targets (AKT1, ERK1/2). YHJG treatment significantly improved neurological function (p < 0.01), reduced infarct volume (p < 0.01), and attenuated neuronal damage. The expression of IL-1β, TNF-α, IL-6, AKT1, and pERK1/2/ERK1/2 significantly increased in the MCAO group (p < 0.01), while YHJG treatment significantly reduced their expression (p < 0.01). PPAR-γ expression significantly increased in the YHJG-H group (p < 0.01). Conclusions: The expression of IL-1β, TNF-α, IL-6, AKT1, and pERK1/2/ERK1/2 significantly increased in the MCAO group, while YHJG treatment significantly reduced their expression. PPAR-γ expression significantly increased in the YHJG-H group. YHJGs could treat IS through diverse ingredients, targets, and pathways by inhibiting inflammatory indices and AKT1 expression, and reducing ERK1/2 phosphorylation.

BACKGROUND:Machine learning (ML) models have been constructed to predict the risk of in-hospital mortality in patients with myocardial infarction (MI). Due to diverse ML models and modeling variables, along with the significant imbalance in data, the predictive accuracy of these models remains controversial. OBJECTIVE:This study aimed to review the accuracy of ML in predicting in-hospital mortality risk in MI patients and to provide evidence-based advices for the development or updating of clinical tools. METHODS:PubMed, Embase, Cochrane, and Web of Science databases were searched, up to June 4, 2024. PROBAST and ChAMAI checklist are utilized to assess the risk of bias in the included studies. Since the included studies constructed models based on severely unbalanced datasets, subgroup analyses were conducted by the type of dataset (balanced data, unbalanced data, model type). RESULTS:This meta-analysis included 32 studies. In the validation set, the pooled C-index, sensitivity, and specificity of prediction models based on balanced data were 0.83 (95 % CI: 0.795-0.866), 0.81 (95 % CI: 0.79-0.84), and 0.82 (95 % CI: 0.78-0.86), respectively. In the validation set, the pooled C-index, sensitivity, and specificity of ML models based on imbalanced data were 0.815 (95 % CI: 0.789-0.842), 0.66 (95 % CI: 0.60-0.72), and 0.84 (95 % CI: 0.83-0.85), respectively. CONCLUSIONS:ML models such as LR, SVM, and RF exhibit high sensitivity and specificity in predicting in-hospital mortality in MI patients. However, their sensitivity is not superior to well-established scoring tools. Mitigating the impact of imbalanced data on ML models remains challenging.

Currently, an increasing number of individuals diagnosed with diabetes mellitus (DM) are opting for combined functional substances in edible plant products, like herbal prescription or traditional Chinese medicine (TCM), to enhance the efficacy of blood glucose and lipid profile control. Among various TCM-included treatments available, Gegen Qinlian decoction (GQD) is frequently utilized. Nevertheless, the efficacy and safety of GQD and its main constituents (berberine, puerarin, etc.) in managing glucolipid metabolic disorders (GLMD) in DM remain under considerable debate. This overview aims to provide a concise summary of the key findings from systematic review and meta-analysis (SRMAs) on GQD and its main constituents for GLMD in DM, while also assessing the methodological quality of these reviews. A comprehensive search of online databases was conducted with no language restrictions, covering the period from inception to February 20th, 2025. The methodological quality, risk of bias, and strength of evidence of those included SRMAs were accessed. Overlapping randomized controlled trials (RCTs) were excluded, and the results of included meta-analysis were summarized. After screening, 35 studies matching the inclusion criteria were identified. The current evidence indicated that GQD, berberine, and puerarin appeared to be effective in improving the anti-diabetes role. As for blood lipid profile, it is indicated that GQD and berberine intervention could effectively reduce total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL-c) and increase high-density lipoprotein (HDL-c). Consequently, further high-quality primary studies are imperative to establish a more conclusive understanding of GQD and its main constituents for GLMD in DM.

BACKGROUND:Ischemic stroke is a life-threatening cerebrovascular disease with limited therapeutic options. During the progression of acute ischemic stroke (AIS), neutrophil-involved inflammation mediated by high mobility group box 1 (HMGB1) considerably contributes to intensification of neuronal injury. Siegesbeckia orientalis L. (SO), one of the primary sources of Sigesbeckiae Herba, is promising in anti-neuroinflammation and neutrophil function modulation. Consequently, it is supposed that SO could fight against neuronal inflammatory injury following AIS. PURPOSE:The current study struggles to explore the ameliorative effects of ethanol extract of SO (EESO) on neuronal inflammatory injury following AIS, and dissect the related mechanisms focusing on HMGB1-driven neutrophil recruitment and neutrophil extracellular traps (NETs) generation. METHODS:Murine photothrombotic stroke model was established to evaluate the ameliorative effects of EESO administration against AIS. Histopathological examination and immunofluorescence staining were conducted for the observation of cerebral neuronal injury, neutrophil infiltration and NETs generation. Additionally, inflammatory indexes and serum HMGB1 levels were also detected through qPCR and ELISA, respectively. In vitro, the effects of EESO-containing serum administration on neutrophil migration and NETs generation were also assessed. HMGB1-overexpressed mimic transfection, cellular thermal shift assay and coimmunoprecipitation were employed to investigate whether the compounds from EESO-containing serum targeted HMGB1 to block the receptor for advanced glycation end products (RAGE)-CD11b interaction. Furthermore, potential active compounds of EESO targeting HMGB1 were screened and verified. RESULTS:EESO administration alleviated photochemically induced murine AIS as revealed by remarkably reducing infract volume as well as improving cerebral blood flow and neurological functions. Moreover, EESO administration prominently mitigated secondary neuronal injury, restrained neutrophil infiltration and NETs generation, as well as lowered the levels of serum pro-inflammatory mediators and HMGB1. In vitro, the compounds in EESO-containing serum directly interacted with neuron-derived HMGB1. HMGB1-driven neutrophil migration and NETs generation through the RAGE-CD11b interaction were also reversed by EESO-containing serum administration. Additionally, isoimperatorin, 4,7-dimethyltetral-1-one, perillartine and darutigenol, as the active components, contributed to the suppressive effects of EESO on neutrophil migration and NETs generation driven by HMGB1. CONCLUSION:In the present study, it was demonstrated that HMGB1 promoted interaction between CD11b and RAGE to drive NETs generation for the first time. Furthermore, EESO was proved to target neuron-derived HMGB1 to inhibit neutrophil infiltration and NETs generation against neuronal inflammatory injury poststroke, which was attributed to the components absorbed in the blood including isoimperatorin, 4,7-dimethyltetral-1-one, perillartine and darutigenol.