Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Dipsaci Radix is a commonly used Chinese herbal medicine in China, with triterpenoid saponins as the main active components. β-Amyrin synthase, a member of the oxidosqualene cyclase superfamily, plays a crucial role in the biosynthesis of oleanane-type triterpenoid saponins. Asperosaponin Ⅵ is an oleanane-type triterpenoid saponin. To explore the β-amyrin synthase genes involved in the biosynthesis of asperosaponin Ⅵ in Dipsacus asper, this study screened the candidate genes from the transcriptome data of D. asper. Two β-amyrin synthase genes, Da OSC1 and Da OSC2, were identified by phylogenetic analysis and correlation analysis. The coding sequences of Da OSC1 and Da OSC2 were 2 286 bp and 2 295 bp in length, encoding 761 and 764 amino acids,respectively. Multiple sequence alignments showed that Da OSC1 and Da OSC2 had three conserved motifs( DCTAE, QW, and MWCYCR) unique to the oxidosqualene cyclase family. Real-time quantitative PCR results showed that Da OSC1 and Da OSC2 had the highest expression levels in the roots. Compared with normal growth conditions, the low-temperature treatment significantly upregulated the expression of Da OSC1 and Da OSC2. Agrobacterium-mediated transient expression of Da OSC1 and Da OSC2 in Nicotiana benthamiana resulted in the production of β-amyrin, which suggested that Da OSC1 and Da OSC2 were able to catalyze the synthesis of β-amyrin. This study clarified the catalytic functions of two β-amyrin synthases in D. asper, analyzed their expression patterns in different tissue and at low temperatures. The findings provide a foundation for further studying the biosynthetic pathway and regulatory mechanism of asperosaponin Ⅵ in D. asper.
Intramolecular Transferases/chemistry* ; Phylogeny ; Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Dipsacaceae/classification* ; Saponins/metabolism* ; Oleanolic Acid/metabolism*

Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*

To clarify the species, pathogenicity, and distribution of the pathogens causing the root rot of Atractylodes lancea in Hubei province, the tissue separation method was used to isolate the pathogens from root rot samples in the main planting areas of A. lancea in Hubei. Based on the preliminary identification of the Fusarium genus by the internal transcribed spacer(ITS) sequence, three housekeeping genes, EF1/EF2, Btu-F-FO1/Btu-F-RO1, and FF1/FR1, were amplified and sequenced. Subsequently, a phylogenetic tree was constructed based on these TEF gene sequences to classify the pathogens. The pathogenicity of these strains was determined using the root irrigation method. A total of 194 pathogen strains were isolated using the tissue separation method. Molecular identification using the three housekeeping genes identified the pathogens as F. solani, F. oxysporum, F. commune, F. equiseti, F. tricinctum, F. redolens, F. fujikuroi, F. avenaceum, F. acuminatum, and F. incarnatum. Among them, F. solani and F. oxysporum were the dominant strains, widely distributed in multiple regions, with F. solani accounting for approximately 54% of the total isolated strains and F. oxysporum accounting for approximately 34%. Other strains accounted for a relatively small proportion, totaling approximately 12%. The results of pathogenicity determination showed that there were certain differences in pathogenicity among strains. The analysis of the pathogenicity differentiation of the widely distributed F. solani and F. oxysporum strains revealed that these dominant strains in Hubei were mainly highly pathogenic. This study determined the species, pathogenicity, and distribution of the pathogens causing the root rot of A. lancea in Hubei province. The results provide a scientific basis for further understanding the root rot of A. lancea and its epidemic occurrence and scientifically preventing and controlling this disease.
Plant Diseases/microbiology* ; Atractylodes/microbiology* ; Phylogeny ; Plant Roots/microbiology* ; Fusarium/classification* ; China ; Virulence ; Fungal Proteins/genetics*

Astragalus membranaceus(A. membranaceus), a traditional tonic, contains flavonoids as one of its main bioactive components and key indicators for quality standard detection. These compounds predominantly exist in glycosylated forms after glycosylation modification within the plant. The catalytic products of flavonoid glycosyltransferases in A. membranaceus have been reported to be mostly monoglycosides, and only AmUGT28 catalyzes luteolin to form diglycosides. In this study, we cloned a glycosyltransferase gene, AmGT90, from A. membranaceus, with an ORF length of 1 335 bp, encoding 444 amino acids, and the protein had a relative molecular mass of 50.5 kDa. Phylogenetic tree analysis indicated that AmGT90 belongs to the UGT74 family. In vitro enzymatic reaction showed that AmGT90 had broad substrate specificity and could catalyze the glycosylation of various flavonoids, including isoflavones, flavones, flavanones, and chalcones. AmGT90 not only catalyzed the formation of monoglycosides but also diglycosides. In addition, the mechanism of AmGT90 catalyzing the formation of diglycosides from luteolin was preliminarily explored. The experimental results showed that AmGT90 may preferentially recognize C4'-OH of luteolin and then recognize C7-OH to form diglycosides. This study reported a glycosyltransferase from A. membranaceus capable of converting flavonoids into monoglycosides and diglycosides. This finding not only enhances our understanding of the biosynthetic pathways of flavonoid glycosides in A. membranaceus but also introduces a new component for glycoside production through synthetic biology.
Glycosyltransferases/chemistry* ; Flavonoids/chemistry* ; Astragalus propinquus/classification* ; Phylogeny ; Glycosylation ; Plant Proteins/chemistry* ; Substrate Specificity ; Cloning, Molecular ; Amino Acid Sequence

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children. This article presents the evidence and interpretation of the transfusion provisions for children undergoing hematopoietic stem cell transplantation, with the aim of enhancing the understanding and implementation of the "Guideline for pediatric transfusion".
Humans ; Hematopoietic Stem Cell Transplantation ; Child ; Blood Transfusion/standards* ; Practice Guidelines as Topic