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The association between PCOS and the TCM concept of phlegm-damp constitution is well-documented, but their connection via miRNA remains unclear. This study sought to identify key miRNAs implicated in the transition from phlegm-damp constitution to PCOS and to elucidate their associated regulatory networks. We conducted miRNA sequencing on granulosa cells from three groups: healthy controls with a neutral constitution (NP), healthy individuals with a phlegm-damp constitution (NB), and PCOS patients (PC). Principal component analysis (PCA) and differential expression analysis were utilized to pinpoint candidate miRNAs, which were subsequently validated using quantitative real-time PCR (qRT-PCR) in larger cohorts. Bioinformatics, including target prediction, protein-protein interaction (PPI) network construction, and pathway analysis, were employed to delineate the regulatory networks involved. PCA revealed distinct clustering patterns, with NB and PC groups exhibiting closer proximity compared to the NP group. Differential expression analysis identified 24 dysregulated miRNAs in the PC group (20 upregulated, 4 downregulated) and 14 in the NB group (11 upregulated, 3 downregulated), with both groups showing shared enrichment in metabolic, PI3K-Akt, and Ras pathways. Validation confirmed a progressive downregulation of hsa-miR-24-2-5p and hsa-miR-33a-5p across the NP, the NB, and PC groups (P<0.05), whereas hsa-miR-374b-5p exhibited differential expression exclusively between NB and PC groups. Network analysis identified five hub genes ( ) and nine risk pathways, including MAPK and Wnt signaling pathways. The constructed miRNA-hub gene-pathway network comprised five miRNA-hub gene pairs and thirteen functional modules. These findings elucidate shared miRNA regulatory mechanisms between phlegm-damp constitution and PCOS, highlighting hsa-miR-24-2-5p and hsa-miR-33a-5p as pivotal mediators in this pathological transition. This provides molecular evidence for the TCM \"constitution-disease correlation\" theory and identifies potential targets for the prevention and treatment of PCOS.

Hypertension pathogenesis increasingly implicates gut microbiota-host crosstalk, where immune regulation bridges gut dysbiosis and renal dysfunction. Phlegm-dampness hypertension-a prevalent Traditional Chinese Medicine (TCM) syndrome typified by metabolic, immune, and renal anomalies-demands novel interventions. Modified Zexie Decoction (MZXD), a TCM formula with documented antihypertensive and anti-inflammatory properties, may target the gut-immune-kidney axis. This study investigated MZXD's efficacy in Stage I phlegm-dampness hypertension via this axis. Thirty Stage I phlegm-dampness hypertension patients received MZXD for 42 days. Pre- and post-treatment measurements included blood pressure, serum immune markers, renal function parameters, gut microbiota, and short-chain fatty acids (SCFAs). MZXD significantly reduced systolic/diastolic blood pressure (P < 0.05). Gut microbiota diversity increased, shifting toward healthy profiles. SCFA levels rose markedly (P < 0.01). Immune markers (P < 0.05) and renal function improved (P < 0.05). MZXD alleviates phlegm-dampness hypertension by modulating the gut-immune-kidney axis: enhancing microbial diversity, boosting SCFAs, attenuating inflammation, and improving renal function. This first systematic validation positions MZXD as a promising multi-target therapy. Future studies should explore clinical scalability and mechanistic depth.

Background: Obesity is conventionally considered a risk factor for multiple metabolic diseases, such as dyslipidemia, type 2 diabetes, hypertension, and cardiovascular disease (CVD). However, not every obese patient will progress to metabolic disease. Phlegm-dampness constitution (PDC), one of the nine TCM constitutions, is considered a high-risk factor for obesity and its complications. Alterations in the gut microbiota have been shown to drive the development and progression of obesity and metabolic disease, however, key microbial changes in obese patients with PDC have a higher risk for metabolic disorders remain elusive.Methods: We carried out fecal 16S rRNA gene sequencing in the present study, including 30 obese subjects with PDC (PDC), 30 individuals without PDC (non-PDC), and 30 healthy controls with balanced constitution (BC). Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt.Results: Obese individuals with PDC had higher BMI, waist circumference, hip circumference, and altered composition of their gut microbiota compared to non-PDC obese individuals. At the phylum level, the gut microbiota was characterized by increased abundance of Bacteroidetes and decreased levels of Firmicutes and Firmicutes/Bacteroidetes ratio. At the genus level, Faecalibacterium, producing short-chain fatty acid, achieving anti-inflammatory effects and strengthening intestinal barrier functions, was depleted in the PDC group, instead, Prevotella was enriched. Most PDC-associated bacteria had a stronger correlation with clinical indicators of metabolic disorders rather than more severe obesity. The PICRUSt analysis demonstrated 70 significantly different microbiome community functions between the two groups, which were mainly involved in carbohydrate and amino acid metabolism, such as promoting Arachidonic acid metabolism, mineral absorption, and Lipopolysaccharide biosynthesis, reducing Arginine and proline metabolism, flavone and flavonol biosynthesis, Glycolysis/Gluconeogenesis, and primary bile acid biosynthesis. Furthermore, a disease classifier based on microbiota was constructed to accurately discriminate PDC individuals from all obese people.Conclusion: Our study shows that obese individuals with PDC can be distinguished from non-PDC obese individuals based on gut microbial characteristics. The composition of the gut microbiome altered in obese with PDC may be responsible for their high risk of metabolic diseases.

Gastric cancer (GC) develops in a complex tissue environment, the tumor microenvironment (TME), which it relies on for persistent proliferation, migration, invasion and metastasis. Non-malignant stromal cell types within the TME are regarded as a clinical meaningful target with the lower risk of resistance and tumor relapse. Studies have revealed that the Xiaotan Sanjie decoction, which is formulated on the basis of the theory of phlegm syndrome, a Traditional Chinese Medicine concept, modulates released factors such as transforming growth factor-β from tumor cells, immune cells, cancer-associated fibroblasts, extracellular matrix, as well as vascular endothelial growth factor involved in the process of angiogenesis within the TME. Clinical studies have also shown that the Xiaotan Sanjie decoction is associated with favorable survival and quality of life. The present review aimed to interpret the hypothesis that Xiaotan Sanjie decoction has the ability to normalize the GC tumor cells by influencing functions of stromal cells within the TME. The possible association between phlegm syndrome and the TME in GC was discussed in the present review. Overall, Xiaotan Sanjie decoction may be suitable to be added to tumor cell-directed agents or emerging immunotherapies becoming a desirable modality in the management of GC and acquire improved outcomes for patients with GC.

A 68-year-old male patient was hospitalized with a giant arch aneurysm. Using 3D printing guidance, the aneurysm was successfully sealed, but post-surgery, he developed severe complications. He remained in the intensive care unit for 52 days for observation and was discharged for rehabilitation. During follow-up, recurrent blood in sputum prompted a computed tomography scan revealing intracavitary leakage. After multiple treatments and assessments, it was determined that type IV endoleak resulted from the proximal bare stent graft puncturing the membranous portion of the aortic stent. Subsequent stent graft procedures and precise embolization successfully closed the leakage, resolving the symptoms.

To evaluate the clinical efficacy of Xiaonang Yusi decoction (XNYSD, ) in patients with phlegm-dampness type polycystic ovary syndrome (PCOS) undergoing fertilization and embryo transfer (IVF-ET), and to investigate its underlying mechanism by examining the arachidonic acid (AA) metabolic pathway. Women undergoing IVF-ET were divided into a treatment group (TCM treatment), a phlegm-dampness PCOS group, and a tubal factor control group (  32 each); all received a GnRH antagonist protocol. The study evaluated IVF-ET laboratory and clinical outcomes, alongside changes in TCM syndrome scores. To elucidate the therapeutic mechanism, follicular fluid AA metabolites were quantified by targeted metabolomics. These data were integrated with a network pharmacology analysis to link the active ingredients of Xiaonang Yusi decoction, PCOS targets, and differential metabolites. A protein-protein interaction (PPI) network was then constructed (STRING) and analyzed for GO/KEGG enrichment (DAVID) to systematically clarify the treatment's mode of action. Clinical findings demonstrate that Traditional Chinese Medicine (TCM) intervention significantly ameliorates phlegm-dampness symptoms in PCOS patients, with marked improvements in embryo implantation rate (52.0% vs. 28.0%), clinical pregnancy rate (67.9% vs. 29.0%), and ongoing pregnancy rate (60.7% vs. 29.0%) (all  0.05), while showing no significant intergroup differences in early miscarriage rates (  0.05). Metabolomic profiling revealed significantly elevated levels of four arachidonic acid metabolites, including 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), in follicular fluid of PCOS patients compared to controls (  0.05), with TCM treatment effectively reducing 15(S)-HETE concentrations (  0.05). Network pharmacological analysis suggests that Xiaonang Yusi Decoction may modulate PCOS pathophysiology through targeting 15(S)-HETE-mediated pathways, acting on core targets including ESR1 and SIRT1, and influencing critical signaling pathways such as cancer-related pathways, lipid metabolism, and PI3K-Akt signaling. Molecular docking results show favourable interactions, indicating the active compound can spontaneously bind and modulate multiple key targets. Xiaonang Yusi Decoction significantly improves TCM syndrome manifestations and IVF-ET outcomes in phlegm-dampness PCOS patients, enhancing embryo quality and pregnancy rates. The therapeutic effects appear mediated through regulation of arachidonic acid metabolites, particularly 15(S)-HETE, in follicular fluid. Network pharmacology analysis has preliminarily elucidated the underlying mechanisms, providing novel evidence for TCM-based PCOS treatment strategies.

Background: According to the theory of traditional Chinese medicine, phlegm and blood stasis (PBS) is the pathological basis for coronary heart disease (CHD). This study aimed to explore the biological basis of PBS syndrome in CHD. Methods: Using a strategy that integrated RNA-seq, DIA-based proteomics, and untargeted metabolomics on 90 clinic samples, we constructed a “gene–protein–metabolite” network for CHD-PBS syndrome. We expanded the sample size and validated the differential genes and metabolites in the network through enzyme-linked immunosorbent assay. Results: Our findings revealed that the “gene–protein–metabolite” network of CHD-PBS syndrome included 33 mRNAs, four proteins, and 25 metabolites. JNK1, FOS, CCL2, CXCL8, PTGS2, and CSF1 were all poorly expressed in the PBS group during the sequencing stage, whereas arachidonic acid (AA) was highly expressed. During the validation stage, JNK1, AP-1, CCL2, and CXCL8 were poorly expressed, whereas PTGS2, CSF1, and AA were highly expressed. The area under the receiver operating curve was as follows: CSF1 [0.9635, 95%CI (0.9295, 0.9976)] >JNK1 [0.9361, 95% CI (0.8749, 0.9972)] >CXCL8 [0.8953, 95% CI (0.8222, 0.9684)] > CCL2 [0.8458, 95% CI (0.7676, 0.9241)] >AP-1 [0.7884, 95%CI (0.6869, 0.8899)]. The logistic regression model composed of CSF1 and JNK1 showed the greatest diagnostic value and significance for PBS syndrome. Conclusion: PBS syndrome is characterized by low levels of FOS, AP-1, CCL2, CXCL8, and JNK1 and elevated levels of PTGS2 and CSF1, implying that the AA metabolism is abnormal and that the JNK/AP-1 pathway is inhibited. PBS syndromes, as a subtype of CHD, may have unique molecular changes. Background. Globally, coronary heart disease (CHD) is the leading cause of death, and this would likely continue until 2030 ( Mirzaei et al., 2009 , 95, 740–746). According to the disease course, CHD can be classified as chronic stable CHD (or chronic coronary syndrome) and acute coronary syndrome (ACS) ( Katus et al., 2017 ; Knuuti, 2019 ). Although stable CHD is not as lethal as ACS, it has a varied incidence range and patients with CHD have prolonged angina. Some symptoms of stable angina are alleviated with pharmacological therapy, but it cannot eliminate recurrent angina ( Rousan et al., 2017 ). The clinical outcomes were not significantly improved in patients who underwent revascularization compared with those who received optimal pharmacological therapy ( Shaw et al., 2008 ; Antman and Braunwald, 2020 ). A bottleneck appears to exist in CHD treatment, and traditional Chinese medicine (TCM) can act as a favorable complement. Because of its individualized treatment approach, TCM is widely practiced in eastern civilizations ( Teng et al., 2016 ). TCM has become a principal complement in western countries ( Wieland et al., 2013 ). Like “disease” is used in western medicine, “syndrome” is used in TCM to comprehend anomalous human conditions on the basis of patients’ symptoms, tongue, and pulse ( Li et al., 2012 ). On the basis of disease-syndrome diagnose, a TCM doctor can subclassify CHD patients into various categories, such as phlegm and blood stasis (PBS) syndrome, cold congealing and Qi stagnation syndrome, and Qi stagnation and blood stasis syndrome. PBS syndrome has recently emerged as a hot research topic in the TCM field. Objective diagnosis, expert consultations, and efficacy evaluation scales have been developed for PBS syndrome ( Ren et al., 2020 ; Liu et al., 2021 ; Zheng et al., 2022 ). The concept of “omics” originates from the genome. It refers to the vocabulary generated by biological molecules at different levels to describe high-sequence molecular biological data resources ( Dai and Shen, 2022 ). RNA, protein, and metabolites decipher the essence of complex etiologies, and the integration of transcriptomics, proteomics, and metabolomics are becoming a promising research mode ( Pan et al., 2022 ). Multi-omics studies have revealed the biological characteristics of APOE transgenic mice, bronchopulmonary dysplasia, and plant tolerant to heavy metals ( Singh et al., 2016 ; Lal et al., 2018 ; Mohler et al., 2020 ). Over the past few years, many academic achievements related to CHD-PBS syndrome have been accrued in the single-omic area. For example, Zhou identified the differential metabolites between PBS syndrome and Qi and Yin deficiency syndrome by using the urine samples of 1072 volunteers. Some of the specific metabolites of PBS syndrome are pyroglutamic acid, glutaric acid, glucose, mannitol, and xanthine ( Zhou et al., 2019 ). Li’s metabolomic study suggested that valine, leucine, isoleucine, and glycerol phospholipid metabolism could represent PBS syndrome ( Zheng et al., 2022 ). Although some progress has been made in the understanding of PBS syndrome in CHD through the studies conducted, some issues still exist, such as a single-omics level, a lack of in-depth research, an inability to verify each other’s research results, and a lack of validation of research conclusions. Overall, a systematic description of the biological foundation of PBS syndrome is lacking. Thus, the present study utilizes system biology methodologies and constructs a multi-omics network by integrating differential genes, proteins, and metabolites to systematically and comprehensively reveal the biological basis of CHD-PBS syndrome. The current study explored 1) the characteristics of the transcriptome, proteome, and metabolome for CHD-PBS syndrome; 2) the “gene–protein–metabolite” network based on differential genes (DGs), differential proteins (DPs), and differential metabolites (DMs); 3) the key biological process and metabolic pathway most related to PBS syndrome; and 4) quantitative results and the diagnostic potential of biomarkers for PSB syndrome. Materials and methods. Multi-omics sequencing, bioinformatics analysis, and clinical validation research strategy. We collected the blood samples from healthy subjects as well as CHD patients with PBS and non-phlegm and blood stasis (NPBS) syndrome to compare the differences between them by subjecting the samples to the transcriptome, proteome, and metabolomics analyses. Bioinformatics analysis identified differential molecules as well as related biological processes and pathways. Next, the “gene–protein–metabolite” network was constructed using the MetaboAnalyst database, String database, and Cytoscape software. We selected molecules with strong centrality and biological association as potential PBS syndrome biomarkers and recruited more volunteers for further validation by enzyme-linked immunosorbent assay (ELISA). Finally, the ROC curve was utilized to assess the level and diagnostic efficacy of various molecules ( Figure 1) .

Background Isoproterenol (ISO), a synthetic on selective β-adrenergic agonist, provides a simple and non-invasive method for inducing myocardial injury with lower mortality and higher reproducibility. Phlegm-damp syndrome, as known as “Tanshi” in Chinese, is one of Traditional Chinese Medicine (TCM) syndrome differentiation, which plays an important role in the development of cardiovascular diseases. However, the underlying mechanism remains unknown. Methods In our present study, a myocardial injury mouse model was introduced by ISO administration combined with high temperature and high humidity and high-fat diet to simulate phlegm-damp syndrome. Nontargeted metabolomics with LC–MS/MS was adopted to reveal serum metabolism profile for elucidating the possible molecular mechanism. Results The results of our study showed that phlegm-damp syndrome promoted ISO-induced myocardial injury by aggravating left ventricular hypertrophy and fibrosis, and increasing cardiac index. Our study also confirmed the presence of specific metabolites and disturbed metabolic pathways by comparing ISO mice and Tanshi mice, mainly including glycerophospholipid metabolism, arginine–proline metabolism, and sphingolipid signaling pathway. The lysoPCs, PCs, SMs, Sphingosine, and L-Arginine were the main metabolites that showed a difference between ISO and Tanshi mice, which might be the result of the underlying mechanism in the promotion of ISO-induced myocardial injury in mice with high temperature and high humidity and high-fat diet. Conclusion Our current study provides new insights into contribution of metabolism disorder in promotion of ISO-induced myocardial injury in mice with high temperature and high humidity and high-fat diet, and new targets for clinical diagnosis and pharmacologic treatment of cardiovascular disease with phlegm-damp syndrome.

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder characterized by hyperandrogenism, insulin resistance, and reproductive dysfunction. Accumulating evidence indicates that gut microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), contribute to PCOS pathogenesis. However, subtype-specific alterations, especially in Traditional Chinese Medicine (TCM)-defined phlegm-dampness PCOS, remain insufficiently explored. Objective This study aimed to comprehensively compare gut microbial composition, SCFA concentrations, and their associations with anthropometric, clinical, and biochemical indicators in women with phlegm-dampness PCOS, non-phlegm-dampness PCOS, and healthy controls. Methods In this cross-sectional analysis, 54 women were recruited and stratified into phlegm-dampness PCOS ( n  = 17), non-phlegm-dampness PCOS ( n  = 18), and healthy control ( n  = 19) groups. Anthropometric measurements, reproductive and metabolic indices, and serum hormones were assessed. Fecal SCFAs were quantified via gas chromatography, and gut microbial profiles were characterized using 16 S rRNA gene sequencing. Bioinformatic and statistical analyses included diversity indices, taxonomic abundance, principal component and clustering analyses, and correlation networks linking microbiota, SCFAs, and host phenotypes. Results Phlegm-dampness PCOS exhibited significantly reduced α-diversity compared with controls ( p  < 0.05) and distinct microbial profiles across multiple taxonomic levels. Key alterations included enrichment of Blautia wexlerae and depletion of Faecalibacterium and Alistipes. Fecal butyrate and propionate levels were markedly reduced in phlegm-dampness PCOS versus controls ( p  < 0.01). Correlation analyses revealed Blautia wexlerae was positively associated with BMI, waist circumference, hirsutism, and acanthosis nigricans, while Alistipes shahii correlated with serum testosterone and HOMA-IR. Distinct correlation networks highlighted microbiota–metabolite–host interactions specific to phlegm-dampness PCOS. Compared with healthy controls, the non-phlegm PCOS group (Group B) exhibited intermediate values for microbial diversity and SCFAs; however, most Group B vs. control differences were not significant after adjustment for BMI and age with FDR correction. Conclusion Women with phlegm-dampness PCOS demonstrate more profound gut dysbiosis, SCFA depletion, and distinct microbiota–clinical correlations than non-phlegm-dampness PCOS and healthy controls. These findings underscore the biological relevance of TCM-based subtype stratification and suggest that precision microbiota-targeted interventions may enhance therapeutic outcomes in PCOS. Clinical trial number NA.

Chronic cough and phlegm are frequently reported chronic obstructive pulmonary disease (COPD) symptoms. Prior research classified chronic mucus hypersecretion (CMH) based on the presence of these symptoms for ≥3 months, called chronic bronchitis (CB) if respiratory infection symptoms were present for 1-2 years (Medical Research Council [MRC] definition). We explored whether the COPD Assessment Test (CAT), a simple measure developed for routine clinical use, captures CMH populations and outcomes similarly to MRC and St. George's Respiratory Questionnaire (SGRQ) definitions. We identified CMH in the SPIROMICS COPD cohort using (a) MRC definitions, (b) SGRQ questions for cough and phlegm (both as most/several days a week), and (c) CAT cough and phlegm questions. We determined optimal cut-points for CAT items and described exacerbation frequencies for different CMH definitions. Moderate exacerbations required a new prescription for antibiotics/oral corticosteroids or emergency department visit; severe exacerbations required hospitalization. Results were stratified by smoking status. In a population of 1431 participants (57% male; mean FEV % predicted 61%), 47% and 49% of evaluable participants had SGRQ- or CAT-defined CMH, respectively. A cut-point of ≥2 for cough and phlegm items defined CMH in CAT. Among SGRQ-CMH+ participants, 80% were also defined as CMH+ by the CAT. CMH+ participants were more likely to be current smokers. A higher exacerbation frequency was observed for presence of CMH+ versus CMH- in the year prior to baseline for all CMH definitions; this trend continued across 3 years of follow-up, regardless of smoking status. Items from the CAT identified SGRQ-defined CMH, a frequent COPD trait that correlated with exacerbation frequency. The CAT is a short, simple questionnaire and a potentially valuable tool for telemedicine or real-world trials. CAT-based CMH is a novel approach for identifying clinically important characteristics in COPD that can be ascertained in these settings.