Chronic respiratory diseases cause substantial global morbidity and mortality, yet the shared genetic architecture of pulmonary-function traits, exposure-related phenotypes, and cardiometabolic traits remains incompletely characterised. We applied genomic structural equation modelling to GWAS summary statistics for four pulmonary-function traits, lifetime smoking index, ambient PM2.5 exposure, and arterial oxygen tension to model their shared genetic covariance (mvLung). The mvLung GWAS identified 2,156 loci, including 376 not significant in the individual input GWASs. EFEMP1 was prioritised as a candidate gene, and 41 respiratory and cardiometabolic traits showed significant genetic correlations. Colocalisation, gene-prioritisation, and enrichment analyses identified candidate shared regions and highlighted extracellular-matrix, cell-adhesion, epithelial-barrier, and signalling-related annotations. Drug-target analyses showed pathway-level concordance with previously studied cardiopulmonary drug classes. These findings characterise shared genetic signals across the included traits and nominate candidates for functional follow-up. Because mvLung incorporates exposure-related and oxygenation phenotypes, the results do not represent direct genetic effects on pulmonary function alone, causal mechanisms, or therapeutic efficacy.

BackgroundPrevious studies have demonstrated that carvacrol (Car) ameliorates vascular and hepatic injury in db/db mice, but its low bioavailability limits clinical translation.MethodsTo address this, this study constructed carvacrol-loaded polymeric nanoparticles (Car@PLGA-NPs) to enhance carvacrol bioavailability and fully explore its novel mechanisms of action on islet function and gut homeostasis in a diabetic model. We used C57BL/6J db/db mice to measure serum fasting blood glucose, oral glucose tolerance (OGTT), insulin tolerance (ITT), and lipid profiles. Fecal samples were collected for 16S rRNA sequencing to analyze gut microbiota composition and its correlation with host indices. Pancreatic and intestinal tissues underwent histopathological staining, immunofluorescence, and Western blotting to detect endoplasmic reticulum (ER) stress-related protein expression levels (p-IRE1α, XBP1S, PERK, p-ElF2α).ResultsResults demonstrated that Car@PLGA-NPs, compared to free carvacrol, significantly improved insulin sensitivity, reduced fasting blood glucose, ameliorated dyslipidemia, attenuated inflammation, and mitigated oxidative stress in db/db mice. 16S rRNA sequencing revealed that Car@PLGA-NPs remodeled the gut microbiota composition, with Alloprevotella abundance showing a negative correlation with colonic ER stress proteins (p-IRE1α and p-ElF2α). Immunofluorescence and Western blotting further confirmed that Car@PLGA-NPs significantly suppressed the expression of ER stress-related proteins (p-IRE1α, XBP1S, PERK, p-ElF2α) in both islet and colonic tissues, demonstrating superior efficacy to free carvacrol.ConclusionsCollectively, this study confirms that the PLGA nanocarrier effectively enhances carvacrol bioavailability. Car@PLGA-NPs improve islet function and intestinal homeostasis in diabetic mice by remodeling the gut microbiota and subsequently inhibiting ER stress in pancreatic and intestinal tissues, providing a novel nano-drug delivery system and a “microbiota-ER stress” regulatory axis for diabetes treatment.

Chronic obstructive pulmonary disease (COPD) is characterized not only by local airway inflammation and tissue injury, but also frequently by persistent systemic immune imbalance. After entering the colon, complex carbohydrates can be converted by the gut microbiota into gut-derived molecules such as short-chain fatty acids (SCFAs) and tryptophan metabolites, which may further influence the pulmonary immune status in COPD. These effects are mainly related to the regulation of colonic fermentation kinetics and metabolite production by substrate structure, as well as to the actions of selected metabolites on pulmonary immune cells and airway epithelium after intestinal absorption and systemic distribution. The monosaccharide composition, glycosidic linkage type, degree of branching, and degree of polymerization of complex carbohydrates can affect colonic fermentation kinetics and further alter the production ratio of SCFAs and tryptophan metabolites. SCFAs are the main candidate metabolites linked to the regulation of aberrant neutrophil recruitment, alveolar macrophage inflammatory status, the Treg/Th17 balance, and airway epithelial barrier integrity; selected tryptophan metabolites are mainly involved in mucosal defense and epithelial repair. In COPD, bile acids are more likely to be associated with microaspiration from gastroesophageal reflux and local microecological alterations. Complex carbohydrates may participate in the regulation of immune imbalance in COPD by affecting the production, distribution, and local pulmonary actions of gut-derived metabolites, but the quantitative relationships among these processes across the gut, blood, and lung, as well as their specific pulmonary effects in COPD, still require further clarification, particularly in human studies with synchronized sampling.

BackgroundAlzheimer's disease (AD) is the leading cause of dementia worldwide, yet effective therapies for this neurodegenerative disorder remain scarce. Epimedium, a herb with a history of thousands of years in traditional Chinese medicine, exhibits diverse biological activities and holds potential therapeutic effects against Alzheimer's disease. However, studies on its modern pharmacological mechanisms remain relatively limited.MethodsTCMSP and PubChem were used to retrieve Epimedium constituents, and SwissTargetPrediction was used to predict potential targets. GeneCards, OMIM, and GEO databases were used to identify targets associated with AD. The AD model was established by intragastric administration of AlCl3 combined with intraperitoneal injection of D-galactose, with the normal saline group serving as controls. Cognitive function was assessed by the Morris water maze, and histopathological changes were observed by H&E staining. ELISA detected IL-1β and TNF-α levels, and qRT-PCR detected KAT2B, NF-κB, IL-1β, and TNF-α expression.ResultsWe identified 172 key targets, with KAT2B and ACACB determined as core genes through transcriptomic screening. In vivo studies showed that Epimedium significantly ameliorated cognitive deficits and alleviated histopathological damage in hippocampal neurons. Furthermore, Epimedium suppressed neuroinflammation by reducing IL-1β and TNF-α levels and modulated the mRNA expression of key targets (KAT2B, NF-κB) in the hippocampus.ConclusionEpimedium improves pathological alterations in the hippocampal tissue and alleviates cognitive and behavioral impairments in rats by modulating neuroinflammation through KAT2B, thereby providing a scientific basis for its potential application and development as a therapeutic agent.

Immunoglobulin A nephropathy (IgAN), the most common primary glomerular disease and a leading cause of end-stage kidney disease (ESKD), is associated with cardiovascular and metabolic abnormalities. To explore these genetic overlaps, we integrated large-scale GWAS data from IgAN, 21 pan-vascular diseases (PVDs), 13 metabolic traits, 11 immune cell phenotypes, and established IgAN risk factors. Cross-trait analyses (LDSC, GNOVA, SUPERGNOVA) revealed significant genetic correlations between IgAN and multiple PVDs, including coronary artery disease, heart failure, stroke, aortic aneurysm, and varicose veins. Multi-omics prioritization (TWAS, SMR, MAGMA, and fastBAT) identified shared variants and candidate genes associated with immune regulation, lipid transport, and cardiovascular function. Gene expression profiling demonstrated enrichment of these genes in endothelial cells, macrophages, spleen, lung, and blood. Drug repurposing analysis based on gene-drug matching scores (>0.5) identified promising therapeutic candidates, including immunosuppressants (prednisolone, cyclosporine, azathioprine), lipid-lowering agents (pitavastatin, fenofibrate), and the antiplatelet drug aspirin. These findings offer novel opportunities for precision medicine and drug repurposing in IgAN patients with cardiometabolic disorders.

Vitamin D receptor (VDR) signaling plays a crucial role in skin homeostasis and represents a promising therapeutic target for inflammatory senescence-associated skin aging. This review examines the roles of VDR signaling in inflammatory senescence-associated skin aging. We summarize the actions of VDR through chromatin modification, transcriptional regulation, and coregulator recruitment, which collectively modulate inflammation and cellular senescence in aging skin. Recent findings highlight the protective role of VDR against inflammatory responses and aging processes through multiple pathways, including NF-κB suppression and regulation of senescence-associated pathways. The review discusses cell-type specific VDR regulation in keratinocytes, immune cells, dermal fibroblasts, and stem cells, emphasizing their distinct roles in skin homeostasis. Current therapeutic approaches encompass vitamin D-based treatments, traditional medicine-derived bioactive compounds, and novel drug delivery systems. Research challenges include limitations in monitoring VDR activity in aging skin and developing effective tissue-specific delivery methods. This analysis emphasizes the therapeutic potential of VDR modulation in aging-related skin conditions and highlights priorities for future investigation of VDR-mediated regulation in inflammatory senescence-associated skin diseases.

Mitochondria, commonly termed the 'cellular powerhouse', produce the majority of cellular adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). In addition to their role in energy synthesis, mitochondria are crucial for maintaining calcium homeostasis, mediating cellular signaling, regulating cell proliferation and apoptosis, and supporting various other physiological processes. In recent years, mitochondria have gained prominence as a critical target for the treatment of metabolic disorders. Research has demonstrated a strong association between mitochondrial dysfunction and the pathogenesis of metabolic diseases, such as insulin resistance, diabetes, metabolic syndrome, cardiovascular diseases, and endocrine tumors. Consequently, understanding the mechanisms of mitochondrial homeostatic imbalance and developing mitochondria-targeted therapeutics hold promise for innovative treatments of metabolic disorder-related diseases. This article seeks to elucidate recent advancements in the understanding of mitochondrial dysfunction's role in metabolic diseases and offers a comprehensive overview of current therapeutic strategies and approaches for addressing this dysfunction.

Major depressive disorder (MDD) and problematic alcohol use (ALC) commonly co-occur, yet the extent, genomic distribution, and biological context of their shared genetic architecture remain incompletely understood. Here, we integrated genome-wide and local genetic architecture analyses with tissue, spatial, single-cell, and multi-omics analyses to characterize the shared genetic basis of MDD and ALC. Across methods, the two phenotypes showed a consistent positive genetic correlation (rg = 0.380–0.582). MiXeR estimated that they shared approximately 5479 variants with non-zero additive genetic effects, with the shared component accounting for a larger proportion of the polygenic architecture of ALC than of MDD. Local analyses further indicated that shared genetic covariance was concentrated in a limited number of genomic segments. At the tissue and cellular levels, genetic signals were primarily associated with central nervous system tissues and neuronal lineages, with additional support for oligodendrocyte-related populations; the two phenotypes also differed in the distribution and within-cell-type heterogeneity of disease-relevance scores. Multi-omics integration prioritized MED19 and ACO2 as candidate genes and highlighted processes related to mitochondrial energy metabolism and synaptic function. These findings refine the genomic, tissue, and cellular context of the shared genetic architecture of MDD and ALC and provide prioritized genomic regions, cell types, and candidate genes for validation in independent populations and functional studies.

The progression of chronic obstructive pulmonary disease (COPD) is closely associated with metabolic reprogramming in pulmonary and immune cells. Under stresses such as cigarette smoke exposure, hypoxia, and infection, cells exhibit enhanced glycolysis, impaired mitochondrial oxidative metabolism, and altered tricarboxylic acid (TCA) cycle flux, resulting in abnormal accumulation of metabolites including lactate, succinate, and various acyl-coenzyme A species. These molecules, acting as acyl donors, drive emerging lysine acylation modifications (e.g., lactylation, succinylation, crotonylation), which play pivotal regulatory roles in airway inflammation, oxidative stress, and tissue remodeling by modulating chromatin states of histones or enzymatic activities of non-histone proteins. Studies have shown that histone lactylation (e.g., H3K14la, H4K12la) markedly induces senescence in pulmonary epithelial cells by activating p53 or CD38 expression and exacerbates pathological alterations, whereas succinylation and crotonylation show potential in regulating mitochondrial homeostasis and immune transcriptional programs. Non-histone acylation also plays an important role in feedback regulation of metabolic enzyme function and in proteostasis regulation. To achieve precision diagnosis and treatment, this review established an evidence-grading system based on strength of supporting evidence, indicating that high-strength sites such as lactylation should be prioritized for clinical translation. Future precision prevention and treatment of COPD should shift from mere description of modification abundance to causal validation of key sites, and should prioritize the development of smallmolecule drugs with isoform selectivity, in combination with pulmonary local delivery technologies to balance efficacy and safety. In addition, combined evaluation of specific metabolite levels and the acylation status of key proteins is expected to enable the development of biomarkers with greater predictive capacity, providing scientific support for molecular subtyping and precision intervention in COPD.

The T allele variant of TERT rs2736098 has been associated with an increased risk of lung cancer (LC), yet various studies have yielded inconsistent findings. The purpose of this study is to verify the association between the rs2736098 variant and LC risk, as well as to investigate the differences in this association across different ethnic groups (Caucasians and Asians), various LC subtypes, and distinct smoking statuses. A computer search was conducted for literatures published up to December 20, 2024, in PubMed, Embase, Web of Science, and MEDLINE databases. Data were analyzed using RevMan 5.3, while sensitivity analysis and publication bias were assessed using Stata 14.0. The stability of the results was evaluated with TSA software Registration number: CRD420251030755. The T allele variant of rs2736098 was associated with an increased risk of LC ([OR] = 1.22, 95%CI [1.18, 1.27]), and this association was observed in both Caucasians ([OR] = 1.17, 95%CI [1.14, 1.20]) and Asians ([OR] = 1.26, 95%CI [1.19, 1.34]), with a stronger association in Asians than in Caucasians (Subgroup differences: P = 0.03, I2 = 79.7%). In specific LC subtypes, rs2736098[T] was linked to the risk of NSCLC and LUAD in both Caucasians and Asians (P < 0.05), and the strength of the association with NSCLC and LUAD was greater in Asians than in Caucasians (Subgroup differences: P < 0.05, I2 > 50%). Additionally, rs2736098[T] was associated with the risk of SCLC and LUSC in Asians (P < 0.05), with a similar strength of association for NSCLC and SCLC (subgroup differences: P = 0.87, I2 = 0%), but a stronger association for LUAD than for LUSC (subgroup differences: P = 0.01, I2 = 84.7%). The rs2736098[T] variant was also associated with the risk of LC in both Caucasian smokers/non-smokers and Asian smokers/non-smokers (P < 0.05), and the strength of the association did not vary between Caucasian smokers/non-smokers and Asian smokers/non-smokers (P ≥ 0.05, Subgroup differences: I2 < 50%). Within LC subtypes, rs2736098[T] was primarily associated with the risk of NSCLC in Asian smokers ([OR] = 1.59, 95%CI[1.19, 2.12]) and the risk of LUAD in Asian non-smokers ([OR] = 1.43, 95%CI[1.17, 1.75]). The T allele variant of rs2736098 is associated with LC risk, and Asians have a higher risk of LC, NSCLC and LUAD due to the rs2736098 variant compared to Caucasians. Therefore, there is a difference in the strength of the association between the two populations for LC risk due to the rs2736098 variant. Additionally, regardless of whether Caucasians or Asians are smokers, they are likely to be at risk for LC due to the variant in rs2736098.

Sepsis is a severe infection-related condition commonly seen in clinical practice, characterized by systemic inflammation and multi-organ dysfunction. Astragalus polysaccharides (APS), the primary bioactive compound from the traditional Chinese herb Astragalus, has shown significant anti-inflammatory, immunomodulatory, and antioxidant effects. This study aimed to explore APS's potential in alleviating sepsis by enhancing adrenal cortical hormone production and repairing adrenal microvascular damage, while uncovering the underlying molecular mechanisms. Using an SD rat model, sepsis was induced via cecal ligation and puncture (CLP) surgery. Rats were treated with APS at doses of 400, 600, or 800 mg/kg/day for 7 days. Survival rates, inflammatory cytokine levels, adrenal function, and molecular pathways were evaluated using techniques such as ELISA, HE staining, TUNEL assay, metabolomics, transcriptome sequencing, and validation. Results showed that APS significantly reduced sepsis-induced mortality, elevated serum cortisol levels, and lowered inflammatory cytokines IL-6 and TNF-α. Histological analysis revealed that APS protected the adrenal cortex from apoptosis and inflammatory infiltration. Metabolomic analysis identified 154 differentially regulated metabolites, including significant changes in steroid hormones. Transcriptomic sequencing indicated changes in gene expression, suggesting that APS may inhibit NF-κB activity and promote nitric oxide (NO) production, thus protecting endothelial cells. These findings suggest that APS improves adrenal function and mitigates sepsis-related damage, offering promising therapeutic avenues for sepsis treatment.

This study investigates the mechanism by which bis(2-ethylhexyl) phthalate (DEHP) induces premature ovarian failure (POF) using network toxicology analysis and molecular docking methods. The potential toxic targets of DEHP were identified using databases such as STITCH and SwissTargetPrediction. Disease-related targets associated with POF were retrieved from the GeneCards and OMIM databases. The overlapping targets related to DEHP-induced POF were identified by intersecting the 2 datasets. Furthermore, the protein-protein interaction network was constructed using the STRING database and visualized through Cytoscape software to identify key targets. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on the overlapping targets using the DAVID database. Finally, molecular docking simulations were performed using AutoDock Vina to validate the findings. A total of 116 intersection targets associated with DEHP-induced POF were identified. Among these, 6 key core targets were screened: caspase 3, b-cell lymphoma 2 (BCL2), matrix metalloproteinase 9, peroxisome proliferator-activated receptor gamma, BCL2L1, and cyclin D1. Gene ontology analysis revealed that these targets are primarily involved in response to xenobiotic stimulus, assembly of cyclin-dependent protein kinase holoenzyme complex, and BH domain binding. Kyoto Encyclopedia of Genes and Genomes analysis indicated that these targets are predominantly associated with critical signaling pathways, including the p53 signaling pathway and apoptosis pathways. Additionally, molecular docking studies demonstrated low binding energies between DEHP and the core target proteins, supporting their potential role in the pathophysiology of DEHP-induced POF. This study indicates that caspase 3, BCL2, matrix metalloproteinase 9, peroxisome proliferator-activated receptor gamma, BCL2L1, and cyclin D1 might be potential toxic targets of DEHP-induced POF. It reveals the potential molecular mechanisms underlying DEHP-induced POF, emphasizing the synergistic roles of the p53 signaling pathway and apoptosis in its pathogenesis. These insights provide a novel theoretical framework and identify potential therapeutic targets for the prevention and management of POF.

BACKGROUND:Asthma seriously affects people's survival and quality of life, causing a huge economic burden on society. Modern clinical use of Qianjinweijing Decoction (QJWJ) for the treatment of asthma has achieved good results. However, there is still a lack of research on its efficacy and mechanism of action. Therefore, the purpose of this study is to evaluate the efficacy of QJWJ in the treatment of asthma by systematic review and meta-analysis, and to explore its potential mechanism by network pharmacology. METHODS:The meta-analysis was performed to search for studies published before May 2023 in 7 databases, and Revman 5.4 and R language softwares were used for analysis. Network pharmacology was based on open databases and softwares such as Cytoscape, Perl, Autoduck Vina, and R language. RESULTS:A total of 14 studies were included, involving 1200 patients. The results of the meta-analysis showed that QJWJ could significantly improve the clinical efficacy of asthma patients compared with routine pharmacotherapy (risk ratio = 1.22, 95% CI [1.16, 1.28], P < .00001), enhance lung function, such as FEV1/FVC (mean difference [MD] = 5.63, 95% CI [1.45, 9.81], P = .008), FEV1% (MD = 5.03, 95% CI [4.32, 5.74], P < .00001), PEF (standardized mean difference = 1.37, 95% CI [1.03, 1.71], P < .00001), and increase traditional Chinese medicine syndrome score (MD = -2.50, 95% CI [-4.81, -0.19], P = .03). The results of network pharmacology suggested that the 4 traditional Chinese medicines in QJWJ included 35 active ingredients and 34 potential targets for the treatment of asthma. The core ingredients involved were stigmasterol, β-sitosterol, hederagenin, and gibberellin 7. The core targets were PTGS2, BCL2, and CASP3. The interaction pathway between QJWJ and asthma was mainly enriched in p53, cyclic guanosine monophosphate-protein kinase G, IL-17, and advanced glycation end products-receptor for advanced glycation end products signaling pathways. Molecular docking showed that the core ingredients had good binding activity with the core targets. CONCLUSION:QJWJ is effective in the treatment of asthma, and the therapeutic mechanism may be related to its regulation of inflammation, immunity, and apoptosis.

Objective: To determine the specific quantitative relationship between the hypersensitive C-reactive protein-albumin ratio and short-term clinical outcome measures within 30 days of endovascular therapy in patients diagnosed with acute ischaemic stroke. Method: The retrospective study was conducted at the Jinyang Hospital, China, and comprised data from January 2019 to July 2023 of patients with acute large-vessel occlusive stroke who underwent endovascular therapy. The patients were stratified into two prognostic groups according to their 30-day postoperative modified Rankin Scale scores. Group A had patients with score 0-2 indicating good prognosis, and group B had patients with score 3-6 indicating poor prognosis. Baseline characteristics, vascular risk factors, laboratory test parameters, consultation duration, stroke subtype, responsible vessel and other relevant clinical data was noted and compared between the groups. Data was analysed using SPSS 25. Results: Of the 195 patients, 125(64%) were males and 70(36%) were females. The overall median age was 65 years (interquartile range: 54-74 years). There were 102(52.3%) patients in group A and 93(47.7%) were in group B. Advanced age, hypertension, cerebral oedema, haemorrhagic transformation, baseline National Institutes of Health Stroke score, white blood cell count, infarct volume and hypersensitive C-reactive protein-albumin ratio were significantly different between the groups (p<0.05). Receiver operating characteristic curve analysis revealed that C-reactive protein-albumin ratio predicted the highest value with area under the curve being 0.778. Conclusion: Elevated hypersensitive C-reactive protein-albumin ratio levels independently correlated with adverse clinical outcomes in acute ischaemic stroke patients undergoing endovascular therapy. Key Words: Hypersensitive C-reactive protein-albumin ratio, Endovascular treatment of acute, Acute ischaemic stroke, Prognostic.

Vitamin D receptor (VDR) signaling plays a crucial role in hair follicle biology and represents a promising therapeutic target for various forms of alopecia. This review comprehensively examines the molecular mechanisms of VDR signaling in hair follicle development, cycling, and pathology. We discuss key molecular mechanisms of VDR-dependent gene regulation through chromatin remodeling, transcriptional regulation, and recruitment of coregulatory complexes, which collectively regulate hair follicle homeostasis. Recent advances in understanding VDR genetic polymorphisms and their impact on treatment responses have provided new insights into personalized therapeutic approaches. The review explores current therapeutic strategies, from conventional vitamin D supplementation to emerging targeted delivery systems and combination therapies. We also analyze the challenges and limitations in current research, including the need for improved delivery systems and reliable biomarkers for treatment response prediction. The integration of molecular insights with clinical applications suggests promising directions for developing more effective, personalized treatments for various forms of alopecia. This comprehensive analysis underscores the significance of VDR-targeted approaches in the future management of hair disorders and highlights the importance of continued research in this field.

Observational studies have suggested a potential association between the gut microbiota and chronic obstructive pulmonary disease (COPD); however, the causal relationship between them, as well as the mediating roles of metabolites, inflammatory proteins, and immune cells, remain unclear. This study aims to elucidate the causal relationship between gut microbiota and COPD using genetic approaches and to explore the potential mediating roles of metabolites, inflammatory proteins, and immune cells. To investigate the causal association between gut microbiota and COPD, we first employed univariable Mendelian randomization (UVMR), using the inverse-variance weighted (IVW) method as the primary analytical approach. Robust IVW and penalized IVW methods were further applied to assess the stability of the findings. Subsequently, we performed a two-step multivariable Mendelian randomization (MVMR) analysis to evaluate the mediating effects of 233 metabolites, 91 inflammatory proteins, and 731 circulating immune cell types. Finally, horizontal pleiotropy was corrected using the MR-Egger intercept method, and potential outliers were identified and excluded through MR-PRESSO. The study adhered strictly to the STROBE-MR reporting guidelines. After adjusting for reverse causality, seven gut microbial taxa exhibited a significant causal relationship with COPD. In mediation analyses, CAG-475 was found to influence COPD risk through HLA DR⁺ CD4⁺ T cells (mediation proportion: 0.55%) and IL-10 (15.96%). The Desulfovibrionaceae family primarily mediated COPD risk via lipid metabolism pathways, with free cholesterol in large very-low-density lipoprotein (VLDL) particles accounting for 45.22% of the effect, along with six other lipid-related indicators. Lactobacillus B ruminis exerted its effects through immune markers such as CD19⁺ B cells and CD8dim T cells (mediation proportion: 0.42-0.85%). Conversely, no significant mediation pathways were identified for four microbial taxa, including CAG-485 sp002404675. This study represents the first genetic evidence supporting a causal framework linking gut microbiota to COPD through metabolic, immune, and inflammatory pathways. The findings highlight the critical roles of lipid metabolism dysregulation, immune markers, and inflammatory responses in COPD pathogenesis. However, further research is warranted to explore additional potential mediators and refine the proposed causal network.

Ethnopharmacological relevance The theory of traditional Chinese medicine (TCM) views leukemia as an imbalance between cell growth and death mainly caused by blood stasis. Medicinal plants Aglaia Lour. (family Meliaceae) are traditionally used as folk medicine in China. It possesses the effects of removing blood stasis and swelling for treatment of cancer. Rocaglamide (RocA) is the main active phytochemical component of the genus Aglaia Lour. possessing highly anti-leukemia properties. However, the molecular mechanisms by which RocA exerts its anti-growth effect on erythroleukemia cells are largely unknown. Aim of the study This study aimed to explore the underlying mechanism and glucose metabolism regulation effects of RocA responsible for its anti-erythroleukemia activity. Materials and methods Human erythroleukemic cells were tested for glucose metabolism and treated with glucose deprivation and RocA. MTT assay, cell cycle and apoptosis were used to elucidate growth inhibition. Glucose uptake, glucose consumption and lactate production were evaluated for identification of glucose metabolism. Luciferase assay and ChIP were used to examine the transcriptional activity of c-MYC on the conserved E-boxes binding of the TXNIP (thioredoxin-interacting protein) and HK2 (hexokinase 2) genes. siRNA, shRNA and exogenous transfection were employed to elucidate the effects of TXNIP and HK2 on glucose metabolism. Results We find that glucose deprivation results in growth inhibition, cell cycle arrest and extensive apoptosis in erythroleukemic cells accompanied by downregulation of c-MYC and HK2, responsible for glucose metabolism. The similar results emerged in RocA treated erythroleukemic cells in presence of glucose. RocA is shown to decrease glucose uptake, glucose consumption and lactate production. Mechanistically, RocA dramatically increases TXNIP expression through interference with c-MYC binding to the promoter of the TXNIP gene. RocA also represses c-MYC transcriptional recognition of conserved E-boxes in the HK2 first intron, resulting in HK2 loss. These results implicate c-MYC as an important regulator of TXNIP and HK2 after RocA treatment. TXNIP overexpression or knockdown of HK2 suppresses the proliferation of erythroleukemic cells. Ectopic TXNIP expression restricts glucose uptake and HK2 suppression decreases glucose utilization. Further, our data suggests that loss of HK2 weakens the RocA-driven inhibition effects. We propose repression of c-MYC or the binding by RocA upregulates TXNIP and downregulates HK2, possibly contributes to growth inhibition in human erythroleukemic cells. Conclusions This study uncovers molecular mechanism of RocA against leukemic cells proliferation, linking the anti-erythroleukemia properties of RocA to glucose metabolism.

PURPOSE:Periodontitis and heart failure (HF) impact millions of individuals globally with heavy social and economic burden. Prior research has indicated a connection between them. However, the conclusions have been somewhat inconsistent. Our objective is to confirm, through meta-analysis and Mendelian randomisation studies, whether patients with periodontitis have an increased risk of HF. Therefore, we conducted a comprehensive analysis to explore the causal association between periodontitis and the risk of HF. MATERIALS AND METHODS:In this meta-analysis, we searched online to identify studies involving periodontitis on the risk of HF. The main endpoint assessed in this study was the risk of HF. We used R language to calculate the pooled results and create plots. A random-effects model was employed in the analyses. In the Mendelian randomisation (MR) analyses, we obtained data from public databases. MR analyses were conducted using genome-wide association data for acute and chronic periodontitis. Independent genetic variants associated significantly with each exposure (P 5*10-6) were considered as instruments. The primary analysis employed the inverse variance weighted (IVW) method, which was subsequently supplemented by a series of sensitivity analyses to ensure the robustness and reliability of the findings. RESULTS:Our meta-analysis included three publications, with a total of 21,997 participants. The pooled result demonstrated that periodontitis increased the risk of HF (OR = 1.62, 95% CI 1.29-2.03). Periodontitis increased the risk of heart failure with reduced ejection fraction (HFrEF) with a low level of heterogeneity (OR = 1.99, 95% CI 1.22-3.23) and heart failure with preserved ejection fraction (HFpEF) with little heterogeneity (OR = 1.36, 95% CI 1.00-1.86). In the MR study, acute or chronic periodontitis did not increase the risk of HF. Sensitivity analyses revealed that the causal association estimations were robust. CONCLUSION:In summary, the meta-analysis results indicate that individuals with periodontitis are at a higher risk of HF. The findings from the MR study fail to establish a causal link between the two variables under investigation. To validate this assertion and elucidate the fundamental mechanism, additional research is imperative. CLINICAL SIGNIFICANCE:Based on the current evidence, it cannot be concluded that there is a causal relationship between acute or chronic periodontitis and HF.

Introduction Bronchiectasis is a chronic inflammatory airway disease marked by permanent dilation of the bronchi, recurrent infections, and associated complications. The traditional Chinese medicine Qianjinweijing Decoction (QJWJ) has shown promising results in bronchiectasis treatment with fewer side effects. However, there's a lack of recent comprehensive research evaluating its effectiveness. This review aims to examine the effectiveness and safety of QJWJ in treating bronchiectasis. Methods We searched 7 databases including China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Chinese Science Database, China Biology Medicine Disc (Sinomed), PubMed, Embase, and Cochrane Library, for relevant randomized controlled trials (RCTs) until May 2023, in both Chinese and English. Two researchers conducted a comprehensive review of literature, extracting data based on predefined criteria. The risk of bias was assessed using the Cochrane Collaboration tool, and meta-analysis was performed using RevMan 5.4.1 and RStudio software. Quality of evidence was evaluated using GRADEpro (V3.6.) software. Results This review analysed 35 studies with 2609 patients. The QJWJ group consisted of 1318 patients, while the routine pharmacotherapy (RP) group had 1291 patients. Combining Chinese Herbal Medicine and RP in bronchiectasis treatment showed better with clinical effectiveness [risk ratio (RR)=1.17, 95% confidence interval (CI) (1.13, 1.21), P<0.00001], the percentage of forced expiratory volume in the first second to the predicted value (FEV1%) [mean difference (MD)=3.52, 95% CI (1.48, 5.55), P=0.0007], the ratio of forced expiratory volume to forced vital capacity in the first second (FEV1/FVC) [MD=6.62, 95% CI (1.52, 11.72), P=0.01], peak expiratory flow rate (PEFR) [MD=7.14, 95% CI (5.15, 9.12), P<0.00001], white blood cell count (WBC) [MD=-1.42, 95% CI (-2.53, -0.31), P=0.01], c-reactive protein (CRP) [MD=-7.2, 95% CI (-9.3, -5.1), P<0.00001], and the procalcitonin (PCT) [standardized mean difference (SMD)=-1.39, 95% CI (-2.02, -0.76), P<0.0001], without increasing the incidence of adverse reactions [RR=0.79, 95% CI (0.44, 1.42), P=0.43]. Chinese Herbal Medicine alone also significantly improved bronchiectasis treatment, enhanced clinical effectiveness [RR=1.19, 95% CI (1.04, 1.36), P=0.010], FEV1% [MD=7.09, 95% CI (4.5, 9.68), P<0.00001], and reduced WBC [MD=-2.7, 95% CI (-3.7, -1.7), P<0.00001], CRP [MD=-4.22, 95% CI (-55.32, -3.12), P<0.00001], without increasing the incidence of adverse reactions [RR=0.20, 95% CI (0.01, 4.06), P=0.29]. Conclusion Evidence suggested that QJWJ, used alone or with RP, notably improved bronchiectasis treatment outcomes, enhanced lung function and reduced inflammation without raising adverse reaction risks. Yet, further support from high-quality, large-sample RCTs is needed to strengthen this conclusion.

Background As China enters the period of accelerated development of population aging,the proportion of rheumatoid arthritis cases is increasing,causing a serious burden on society and families.The active ingredients in simiao decoction have improved effect,but there is a lack of relevant studies to analyze the action and mechanism of prescriptions.Objective To observe the intervention effect of simiao decoction on rats with rheumatoid arthritis established by collageninduced arthritis and its effect on vitamin D system and neutrophil extracellular traps(NETs).Methods From November 2021 to January 2023,70 SD female rats were selected.The rats were randomly divided into the blank group(control group),model group(model group),methotrexate group(MTX group),vitamin D group(VD group),Simiao decoction low-dose group(SMT-L group),Simiao decoction medium-dose group(SMT-M group)and Simiao decoction high-dose group(SMT-H group)by random number table method,with 10 rats in each group.The rat model of synovial arthritis was established by collagen induction method and the gavage treatment was started 7 d after modeling.The degree of ankle swelling was assessed,and the arthritis index(AI)score of rats in each group the levels of interleukin 6(IL-6),25-hydroxyvitamin D3[25(OH)D3],NETs in serum of rats and the expression levels of 24-hydroxylase(CYP24A1),1-α hydroxylase(CYP27B1),MPO,vitamin D receptor(VDR)and elastase(NE)in synovial tissue of joint were measured.Results The degree of ankle swelling in the control,MTX,VD,SMT-L,SMT-M and SMT-H groups was lower than that in the model group on day 7,the degree of ankle swelling in the model group was higher than the control group,the SMT-M group was higher than the model group on day 14,the degree of ankle swelling in the model group was higher than the control and MTX groups and lower than the VD,SMT-L,SMT-M and SMT-H groups on day 21,the degree of ankle swelling in the control,MTX,VD,SMT-L,SMT-M and SMT-H groups was higher than the model group,and the difference was statistically significant(P<0.05).The AI score of rats in the SMT-H group was lower than that in the model group on day 14,the AI score in the MTX,VD,SMT-L and SMT-H groups was lower than that in the model group on day 21,the score of rats in the MTX,VD,SMT-L,SMT-M,and SMT-H groups was lower than that in the model group on day 28,the difference was statistically significant(P<0.05).Immunohistochemical results showed significant differences in the expression levels of MPO and TNF-α in synovial tissue among the 7 groups(P<0.05),MPO and TNF-α in the model group were higher than those in the control group,while MPO and TNF-α in the MTX,VD and SMT-H groups were lower than those in the model group,TNF-α in the SMT-M group was lower than that in the model group,and the difference was statistically significant(P<0.05).IL-6 and NETs in the model group were higher than those in the control group,and 25(OH)D3 was lower than that in the control group.IL-6 and NETs in the MTX,VD and SMT-H groups were lower than those in the model group,and 25(OH)D3 was higher than that in the model group.NETs in the SMT-M group were lower than those in the model group,and the difference was statistically significant(P<0.05).CYP24A1 in the model group was higher than that in the control,MTX,VD,SMT-M and SMT-H groups,while CYP27B1 and VDR in the model group were lower than those in the control,MTX,VD,SMT-M and SMT-H groups,MPO was higher than that of the control,MTX,VD,SMT-L,SMT-M and SMT-H groups,and NE was higher than the control,VD,SMT-M and SMT-H groups,and the difference was statistically significant(P<0.05).Conclusion Simiao decoction may inhibit the formation of NETs by regulating the vitamin D system,thereby treating RA.