BackgroundAnti-γ-aminobutyric acid A receptor (GABAA receptor) encephalitis is a rare but severe subtype of autoimmune encephalitis (AE), typically characterized by refractory seizures and rapidly progressive neurological dysfunction. Although structural abnormalities on magnetic resonance imaging (MRI) are frequently observed, the temporal relationships among clinical manifestations, electrophysiological changes, immune activity, and neuroimaging findings remain insufficiently characterized.Case presentationWe report a 61-year-old man with anti-GABAA receptor encephalitis who underwent longitudinal multimodal evaluation. In the early stage, the patient presented with nonspecific vestibular symptoms accompanied by subtle cortical abnormalities on MRI. The disease rapidly progressed to status epilepticus and cognitive impairment. Electroencephalography (EEG) revealed widespread epileptiform discharges, while cerebrospinal fluid (CSF) analysis demonstrated inflammatory changes, and both serum and CSF were positive for anti-GABAA receptor antibodies. Following timely immunotherapy, the patient exhibited rapid clinical improvement, marked attenuation of epileptiform activity, and subsequent antibody negativization. Notably, structural MRI abnormalities persisted and resolved more slowly than clinical and electrophysiological recovery. Translocator protein positron emission tomography (TSPO-PET) using the 18F-DPA714 demonstrated increased tracer uptake in the bilateral temporo-parieto-occipital cortices, indicating persistent neuroinflammation despite clinical improvement.ConclusionsThis case provides longitudinal multimodal observations supporting the concept that anti-GABAA receptor encephalitis may represent a dynamic and potentially reversible disorder of network hyperexcitability rather than a purely structural inflammatory injury. The temporal dissociation between functional recovery and delayed structural resolution highlights the critical value of multimodal monitoring, particularly EEG and immunological biomarkers, in assessing disease activity and guiding immunotherapy.

INTRODUCTION:To investigate the potential anti-atherosclerotic mechanisms of Guanxinkang (GXK), with emphasis on its association with STAT3/CD36 pathway regulation and efferocytosis-related signaling. METHODS:Network pharmacology identified key targets, which were validated by molecular docking and dynamics simulations. ApoE-/- mice and ox-LDL-induced foam cell models established in RAW264.7 macrophages were employed. GXK was administered at 7.22 and 14.43 g/kg/day in vivo and 0.5 and 2 mg/mL in vitro. In vivo and in vitro experiments assessed lipid profiles, plaque formation, inflammatory cytokines, and macrophage efferocytosis. RESULTS:GXK at both low (7.22 g/kg, GXK-L) and high doses (14.43 g/kg with higher concentration, GXK-H) significantly improved serum lipid profiles (reduced TC, TG, LDL-C; increased HDL-C; P<0.05), reduced atherosclerotic plaque area, and suppressed pro-inflammatory cytokines IL-1β and IL-6 while upregulating IL-10 (P<0.05). Mechanistically, GXK significantly inhibited CD36 expression and reduced STAT3 phosphorylation (P<0.01) and modulated efferocytosis- related proteins TIM-4 (upregulated) and CD47 (downregulated) (P<0.05), suggesting enhanced macrophage efferocytosis capacity. Isotanshinone II, a key GXK component, exhibited similar effects in vitro, alleviating lipid accumulation and modulating CD36, STAT3, and efferocytosis-related proteins. DISCUSSION:These results suggest that the therapeutic efficacy of GXK in atherosclerosis is attributed to its multi-target regulatory capacity. By suppressing the STAT3/CD36 axis, GXK not only restricts lipid influx but also restores the homeostatic clearance of apoptotic cells through enhanced efferocytosis. CONCLUSIONS:GXK may exert anti-atherosclerotic effects that are associated with modulation of the STAT3/CD36 axis and efferocytosis-related signaling; however, causal validation requires further investigation.

Heart failure (HF) management remains challenging because patients often show large differences in how well treatments work and in how often adverse drug reactions occur. Traditional pharmacogenomics cannot fully explain these differences. Emerging evidence from pharmacomicrobiomics shows that the gut microbiome represents a previously underappreciated factor influencing drug responses. This review summarizes the two-way interactions between the gut microbiota and key HF drugs, including digoxin, angiotensin receptor-neprilysin inhibitors (ARNIs), ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRAs), and diuretics. On the one hand, gut microbes can change drug effects because they can metabolize drugs and affect host physiological pathways. On the other hand, HF drugs can change the structure and function of the gut microbial community. This review also discusses how microbiome-related features may serve as biomarkers to support personalized treatment and how strategies such as dietary changes and microbiota-targeted therapies may improve clinical outcomes. Although evidence remains limited, and certain methods require further refinement, integrating microbiome insights into HF treatment may support more precise and individualized treatment strategies and help address current therapeutic limitations.

BackgroundIn recent years, significant attention has been directed toward the development of therapeutic agents targeting cognitive and motor dysfunction following ischemic stroke. Our research team synthesized SHPL-49, a salidroside derivative, which has demonstrated neuroprotective effects in rat models of ischemic stroke in prior studies. However, the underlying mechanisms remain poorly understood. This study aims to evaluate the therapeutic potential of orally administered SHPL-49 over a 28-day period in rats with bilateral common carotid artery occlusion (BCCAO), specifically focusing on improvements in cognitive and motor deficits, and to further elucidate its mechanism of action.MethodsA BCCAO rat model was employed to investigate the effects of SHPL-49 on cognitive and motor functions following ischemic stroke. Behavioral performance was assessed using the Morris water maze, shuttle box, running wheel, gait analysis, and rotarod tests. Synaptic remodeling in the brain was evaluated through Golgi staining, Western blotting, and immunofluorescence. In vitro transcriptomic changes in PC-12 cells were analyzed by RNA sequencing to identify SHPL-49-regulated genes associated with synaptic remodeling. Furthermore, primary neurons exposed to oxygen-glucose deprivation/reperfusion (OGD/R) were utilized to validate the potential therapeutic targets of SHPL-49.ResultsSHPL-49 significantly ameliorated cognitive and motor impairments in BCCAO rats. SHPL-49 markedly increased dendritic spine density in brain tissue and promoted synaptic remodeling by upregulating the mRNA expression of synapse-related genes, including MAP-2, SYP, and βIII-tubulin, as well as the expression of the key synaptic protein SYN1. Furthermore, transcriptomic analysis of SHPL-49-treated PC-12 cells suggested that SHPL-49 may regulate synaptic remodeling through CDK4 and CDK5 signaling. Subsequent experiments confirmed that SHPL-49 enhanced the expression of CDK5 and its activator p35 in both primary neurons and BCCAO rats, meanwhile inhibited the cleavage of p35 into p25 (a proteolytic event associated with dendritic spine atrophy and synaptic protein degradation).ConclusionIn summary, SHPL-49 significantly improved memory and motor impairments in BCCAO rats, highlighting the role of synaptic remodeling in this therapeutic effect. The underlying mechanism is closely linked to the modulation of CDK5/p35/p25 signaling pathway. These findings provide important theoretical evidence supporting the potential for the long-term clinical oral application of SHPL-49 in treating ischemic stroke.

Objective:This multicenter, double-blind, randomized controlled trial sought to assess the clinical efficacy of Taoren Honghua Jian (THJ) in patients with coronary artery disease (CAD) exhibiting Qi stagnation and blood stasis syndrome, and investigated its effect on NLRP3 inflammasome expression in peripheral blood mononuclear cells (PBMCs). Methods:One hundred and twenty eligible CAD patients from three Shanghai hospitals were randomized to receive either the THJ granule (18.3 g, twice daily) or placebo for four weeks, with a four-week follow-up. Traditional Chinese Medicine Syndrome Score (TCMSS), Seattle Angina Questionnaire (SAQ), and lipid levels were measured before and after treatments. NLRP3 inflammasome components were examined in PBMCs using quantitative PCR, whereas plasma inflammatory cytokines were detected using ELISA. Results:A total of 120 participants participated in the trial. The THJ group showed reduced TCMSS compared to the placebo group (P < 0.01). After four weeks of intervention, the THJ group scored considerably higher on five SAQ aspects compared to the placebo group (P < 0.01). However, lipid levels showed no significance. In PBMCs, THJ lowered mRNA expression of NLRP3 inflammasome components (NLRP3, ASC, caspase-1, IL-1β, IL-18) (P < 0.01). Patients in the THJ group showed significantly lower plasma levels of IL-1β, IL-2, and IL-18 following therapy compared to the placebo group (P < 0.01). Conclusion:THJ reduces angina symptoms and improves quality of life in CAD patients, which suggests that it suppresses NLRP3-related transcriptional activity and hence reduces pro-inflammatory cytokine production. These data suggest that THJ might be an effective adjuvant treatment for inflammation-driven coronary atherosclerosis.

Cardiovascular disease remains the leading cause of death worldwide, with current therapies facing limitations in efficacy and safety. Chinese Herbal Medicine-Derived Exosomes (CHM-Exos) are nano-sized membrane vesicles secreted by herbal cells, capable of cross-species delivery of bioactive substances. While plant-derived extracellular vesicles have been extensively reviewed, analyses specifically focused on CHM-Exos in cardiovascular contexts remain limited. This review systematically examines the bioengineering applications and therapeutic mechanisms of CHM-Exos in cardiovascular diseases, addressing a critical gap in translational literature. Mechanistically, CHM-Exos show potential to alleviate oxidative stress and modulate vascular cell function, though direct cardiovascular evidence remains preliminary. Key translational barriers-including standardization challenges, scalability constraints, and regulatory uncertainties-are critically discussed, alongside strategies to advance these promising nanocarriers toward clinical application.

Following the publication of the above article, and a Corrigendum (doi: 10.3892/mmr.2025.13581) that was published to rectify errors associated with the published versions of Figs. 5, 8, 9 and 10, an interested reader contacted the Editorial Office to explain that they had identified additional issues in need of further investigation. Subsequently, the authors recognized that there were further problems associated with the manuscript requiring attention which arose while they were organizing materials related to this manuscript. To ensure the scientific integrity of the work, the authors have requested that this article now be retracted from the Journal. In view of these additional issues, the Editor of Molecular Medicine Reports has agreed to the authors' request to retract this paper. Note that all the authors agree to this retraction, and the Editor and the authors apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 29: 102, 2024; DOI: 10.3892/mmr.2024.13226].

To evaluate the clinical efficacy of Taoren Honghua Jian Granule (THJ) in stable coronary artery disease (SCAD) patients with syndrome of qi stagnation and blood stasis, and to investigate its effect on the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in peripheral blood mononuclear cells (PBMCs). In this multicenter, double-blind, randomized controlled trial, 80 eligible SCAD patients from 3 Shanghai hospitals were randomly assigned to receive either the THJ (18.3 g, twice daily, orally) or a matched placebo for 4 weeks 40 in each group, followed by a 4-week follow-up. Chinese medicine (CM) Syndrome Scores and Seattle Angina Questionnaire (SAQ) assessments were conducted pre- and post-intervention. Quantitative PCR was used to analyze mRNA levels of NLRP3 inflammasome components [NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, interleukin (IL)-1β, and IL-18] in PBMCs, while ELISA was used to detect plasma inflammatory cytokines [IL-10, IL-1β, IL-2, IL-6, IL-8, IL-18, tumor necrosis factor (TNF-α), and high-sensitive C-reactive protein (hs-CRP)]. After 4 weeks of treatment, the overall treatment efficacy was higher in the treatment group than in the placebo group; the CM syndrome scores of the two groups were significantly lower after treatment, and the THJ group was considerably lower than the placebo group (P<0.05, P<0.01). The THJ group had significantly higher scores for 5 SAQ dimensions than the placebo group (P<0.01). Both mRNA expression of NLRP3 inflammasome components (NLRP3, ASC, caspase-1, IL-1β, IL-18) decreased in PBMCs (P<0.01). In addition, plasma levels of IL-2, IL-8, IL-18, and TNF-α significantly decreased in THJ group compared with the placebo group after treatment (P<0.05, P<0.01). THJ alleviates angina symptoms and improves quality of life in SCAD patients, potentially through NLRP3 inflammasome inhibition and subsequent attenuation of pro-inflammatory cytokine release. These findings position THJ as a promising adjunct therapy for inflammation-driven coronary atherosclerosis. (Registration No. ChiCTR1900021772)

Metabolic reprogramming of vascular smooth muscle cells (VSMC) is emerging as a central driver of atherosclerotic plaque heterogeneity and instability. VSMCs undergo phenotypic remodeling into osteogenic, macrophage-like, foam cell–like, or pro-inflammatory states through metabolic reprogramming, which actively drives vascular calcification, lipid accumulation, and extracellular matrix degradation. In this review, we summarize the various phenotypes of VSMCs observed during AS development and describe potential molecular pathways linking metabolic reprogramming to phenotypic remodeling. We highlight key regulators, including glucose transporters, pyruvate dehydrogenase kinase 4, 6 - Phosphofructo - 2 - kinase/fructose - 2, 6 - bisphosphatase 3, pyruvate kinase M2, fatty acid synthase, homocysteine, etc., which integrate extracellular stimuli and intracellular metabolic changes to drive VSMCs fate decisions. In addition, we discuss how specific metabolic pathways interact with epigenetic and signaling networks to regulate VSMCs proliferation, apoptosis, calcification, foaming, and aging. Finally, we explore therapeutic opportunities for targeted metabolic regulators, including traditional Chinese medicine, Sirtuin 1 activators, ATP-Citrate Lyase inhibitors, statins, folic acid, etc., providing new strategies to stabilize plaques and slow the progression of AS.

Understanding the molecular underpinnings of CAD is essential for developing effective therapeutic strategies. This study aims to identify and analyze differentially expressed hub biomarkers in the peripheral blood of CAD patients. Based on RNA-seq datasets from the Gene Expression Omnibus database, machine learning algorithms including LASSO, RF, and SVM-RFE were applied. Furthermore, the hub biomarkers were enriched to ascertain their roles in immune cell expression and signaling pathways through GO, KEGG, GSVE, and GSVA. An in vivo experiment was conducted to verify the hub biomarkers. Eleven hub biomarkers (ITM2B, GNA15, PLAU, GNG11, HIST1H2BH, SLC11A1, RPS7, DDIT4, CD83, GNLY, and S100A12) were identified and associated with CD8 + T cells and NK cells. They were mainly involved in immune responses, cardiac muscle contraction, oxidative phosphorylation, and apoptotic signaling pathways. Moreover, ITM2B had the most importance and significance to be the biomarker of CAD patients. In conclusion, these findings point to the possibility of ITM2B as a biomarker on the inflammatory pathogenesis of CAD and suggest new options for therapeutic intervention.

Knee osteoarthritis (KOA) is a chronic degenerative disease that affects the quality of life of middle‑aged and elderly individuals, and is one of the major factors leading to disability. Rongjin Niantong Fang (RJNTF) can alleviate the clinical symptoms of patients with KOA, but the molecular mechanism underlying its beneficial effects on KOA remains unknown. Using pharmacological analysis and in vitro experiments, the active components of RJNTF were analyzed to explore their potential therapeutic targets and mechanisms in KOA. The potential targets and core signaling pathways by which RJNTF exerts its effects on KOA were obtained from databases such as Gene Expression Omnibus, Traditional Chinese Medicine Systems Pharmacology and Analysis Platform. Subsequently, chondrocyte apoptosis was modeled using hydrogen peroxide (H2O2). Cell Counting Kit‑8 assay involving a poly [ADP‑ribose] polymerase‑1 (PARP1) inhibitor, DAPI staining, reverse transcription‑quantitative PCR, Annexin V‑FITC/PI staining and flow cytometry, western blotting and co‑immunoprecipitation analysis were used to determine the therapeutic efficacy of RJNTF on KOA and to uncover the molecular mechanism. It was found that PARP1‑knockdown lentivirus, incubation with PARP1 inhibitor PJ34, medium and high doses of RJNTF significantly reduced H2O2‑induced chondrocyte apoptosis. Medium and high doses of RJNTF downregulated the expression of cleaved caspase‑3, cleaved PARP1 and PAR total proteins, as well as nucleus proteins of apoptosis‑inducing factor (AIF) and migration inhibitory factor (MIF), and upregulated the expression of caspase‑3, PARP1 total protein, as well as the cytoplasmic expression of AIF and MIF, suggesting that RJNTF may inhibit chondrocyte apoptosis through the PARP1/AIF signaling pathway.

Aims To investigate the effects and potential mechanisms of Guan-Xin-Kang (GXK) and its active component Astragaloside IV (AS-IV) in atherosclerosis. Methods Using GXK and AS-IV intervention on high-fat diet-fed macrophage-specific ERK5 knockout LDLR−/− mice (ERK5-MKO/LDLR−/−) and non-transgenic littermate control LDLR−/− mice (NLC/LDLR−/−), we assessed peripheral blood lipid levels, aortic lesion area, cellular composition, and the expression of efferocytosis-related genes. Results GXK significantly reduced blood lipid levels, atherosclerotic plaque area, expression of the macrophage marker MAC3, and increased the expression of the smooth muscle cell marker SMA. It also regulated the expression of efferocytosis-related genes Axl, PPARD, TIM4, and C1QA, regardless of ERK5 knockout. In ERK5 knockout mice, the effects of AS-IV on macrophage marker MAC3, smooth muscle cell marker SMA, and efferocytosis-related genes Axl, PPARD, TIM4, and C1QA were abolished. Conclusion This study confirms the therapeutic effects of GXK on atherosclerotic mice and reveals that GXK targets additional pathways beyond ERK5, whereas its active component AS-IV may specifically target ERK5.

The neuroinflammation triggered by cellular demise plays a pivotal role in ameliorating the injury associated with ischemic stroke, which represents a significant global burden of mortality and disability. The compound SHPL-49, a derivative of rhodioloside, was discovered by our research team and has previously demonstrated neuroprotective effects in rats with ischemic stroke. This study aimed to elucidate the underlying mechanisms of SHPL-49’s protective effects. Preliminary investigations revealed that SHPL-49 effectively alleviates PMCAO-induced neuroinflammation. Further studies indicated that SHPL-49 downregulates the expression of the lysosomal protein LAMP-2 and reduces lysosomal activity, impeding the fusion of lysosomes and autophagosomes, thus inhibiting excessive autophagy and increasing the expression levels of the autophagy proteins LC3-II and P62. Furthermore, SHPL-49 effectively reverses the NF-κB nuclear translocation induced by the autophagy inducer rapamycin, significantly lowering the expression levels of the inflammatory factors IL-6, IL-1β, and iNOS. In a co-culture system of BV2 and PC12 cells, SHPL-49 enhanced PC12 cell viability by inhibiting excessive autophagy in BV2 cells and reducing the ratio of apoptotic proteins Bax and BCL-2. The overall findings suggest that SHPL-49 exerts its neuroprotective effects through the inhibition of excessive autophagy and the suppression of the NF-κB signaling pathway in microglia, thereby attenuating neuroinflammation.

Purpose:Studies consistently show abnormally high levels of lactate acid in cardiovascular disease patients, suggested that targeting lactate production may serve as potential strategies for the treatment in the future. However, observational results may be subject to residual confounding and bias. Methods:This study used the dataset from GWAS database to examine confounding in epidemiologic associations between lactate and cardiovascular diseases. A genome-wide genetic association study using Mendelian randomization (MR) was performed from December 02, 2023 to January 15, 2024 to reduce confounding and enhance causal inference. Primary analysis was conducted using inverse-variance-weighted MR. All studies included patients predominantly of European ancestry. Results:The association between lactate and cardiovascular diseases, including 60801 cases from coronary heart disease, 7018 cases from myocardial infarction, 14334 cases from coronary atherosclerosis, 60620 cases from atrial fibrillation, 54358 cases from hypertension, 71 cases from hypertrophic cardiomyopathy, 47309 cases from heart failure, 7055 cases from stroke, 7193 cases from cardioembolic ischemic stroke, 4373 cases from ischemic stroke caused by large vascular atherosclerosis, 2118 cases from pulmonary embolism, 1230 cases from peripheral artery disease, and 4620 cases from venous thromboembolism. Genetically predicted coronary atherosclerosis was associated with a higher risk of lactate level (OR = 1.950; 95% CI (0.087, 1.249); P = 0.024); this association was also evident for peripheral artery disease (OR = 1.003; 95% CI (0.000, 0.005); P = 0.021). No genetically predicted associations were noted for the other cardiovascular diseases. Conclusion:The findings of this study provide genetic evidence supporting a higher risk of lactate level only in coronary atherosclerosis and peripheral artery disease. However, no genetic association between lactate level and the other cardiovascular diseases.

Background Salvianolic Acid B (SalB) has been proven to delay the progression of atherosclerosis. The therapeutic mechanisms of this compound are unclear. A novel class of short non-coding RNAs, pre-transfer RNA and mature transfer RNA (tsncRNAs) may regulate gene expression. TsncRNAs-sequencing revealed novel therapeutic targets for SalB. This is the first study focusing on tsncRNAs to treat atherosclerosis using SalB. Purpose To explore the potential mechanism of SalB treating atherosclerosis through tsncRNAs. Methods Five groups of mice were created at random: control group (CON), atherosclerosis model group (MOD), SalB with high dose-treated group (SABH), SalB with low dose-treated group (SABL), and Simvastatin-treated group (ST). Aortic sinus plaque, body weight and inflammatory cytokines were evaluated. The Illumina NextSeq equipment was used to do expression profiling of tsncRNAs from serum. The targets of tsncRNAs were then predicted using tRNAscan and TargetScan. The KEGG pathway and GO analysis were utilized to forecast the bioinformatics analysis. Potential tsncRNAs and associated mRNAs were validated using quantitative real-time PCR. Results tRF-Glu-CTC-014 and tRF-Gly-GCC-074 were markedly increased by SalB with high dose treatment and validated with quantitative real-time PCR. Two mRNAs SRF and Arrb related to tRF-Glu-CTC-014 changed consistently. GO analysis revealed that the altered target genes of the selected tsncRNAs were most enriched in protein binding and cellular process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tsncRNAs were most enriched in MAPK signaling pathway. Conclusion SalB can promote the expression of tRF-Glu-CTC-014 to treat atherosclerosis.

OBJECTIVE:To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS:From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS:After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION:JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).

Interferon Gamma Inducible Protein 16 (IFI16) belongs to the HIN-200 protein family and is pivotal in immunological responses. Serving as a DNA sensor, IFI16 identifies viral and aberrant DNA, triggering immune and inflammatory responses. It is implicated in diverse cellular death mechanisms, such as pyroptosis, apoptosis, and necroptosis. Notably, these processes are integral to the emergent concept of PANoptosis, which encompasses cellular demise and inflammatory pathways. Current research implies a significant regulatory role for IFI16 in PANoptosis, particularly regarding cardiac pathologies. This review delves into the complex interplay between IFI16 and PANoptosis in heart diseases, including atherosclerosis, myocardial infarction, heart failure, and diabetic cardiomyopathy. It synthesizes evidence of IFI16's impact on PANoptosis, with the intention of providing novel insights for therapeutic strategies targeting heart diseases.

BACKGROUND:Taoren Honghua Decoction (THD) is a traditional Chinese formula known for enhancing blood circulation and demonstrating clinical efficacy in the treatment of cardiovascular and cerebrovascular diseases. However, the primary active components and the underlying mechanisms by which THD exerts its therapeutic effects on atherosclerosis (AS) remain insufficiently characterized. OBJECTIVE:This study aims to systematically validate the protective effects of THD on AS and elucidate its potential molecular mechanisms through an integrative approach involving network pharmacology, in vivo, and in vitro experiments. METHODS:The main active ingredients and corresponding targets of all traditional Chinese medicines in THD were collected from the TCSMP and BATMAN-TCM databases. Potential targets of AS were identified using the OMIM, DrugBank, DisGeNET, and CTD databases, and AS microarray gene data were obtained from the GEO database. A drug active ingredient-target relationship network and a PPI network were constructed using Cytoscape 3.9.2 software. The molecular functions of the core targets were annotated through GO and KEGG enrichment analyses to further elucidate the potential molecular mechanisms of THD's anti-AS effects. The ApoE-/-mouse AS model was constructed through a high-fat diet (HFD), and RAW264.7 macrophage model was induced with ox-LDL to further validate the results of network pharmacology. RESULTS:Network pharmacology analysis revealed that the main five active ingredients of THD include quercetin, apigenin, luteolin, kaempferol, and tanshinone IIA. Subsequently, by analyzing the intersection genes of the main active ingredient targets of THD and the AS targets, a total of ten core targets were identified: TP53, PPARG, JUN, AKT1, INS, IL6, SIRT1, TNF, ESR1, and STAT3. These are considered the core targets of THD in the treatment of AS. The GO and KEGG enrichment analysis results indicate that THD may exert anti-AS effects by regulating lipid metabolism and the PI3K-AKT signaling pathway. In vivo and in vitro experiments showed that THD reduced circulating lipid levels, decreased intraplaque lipid accumulation, and increased intraplaque collagen fiber content in HFD-induced ApoE-/- mice. Additionally, THD reduced ox-LDL-induced macrophage-derived foam cell formation, inhibited the expression of inflammatory factors IL-6 and TNF-α, and promoted the expression of cholesterol efflux regulatory proteins PPARγ, ABCA1, and ABCG1. Notably, the autophagy inhibitor 3-MA reversed these effects, confirming that THD's action involves autophagy activation, evidenced by increased LC3II/I and decreased p62 levels. CONCLUSION:This study demonstrates that THD exerts significant anti-AS effects through the inhibition of the PI3K/AKT signaling pathway and the activation of autophagy, thereby promoting cholesterol efflux and mitigating inflammation. By integrating network pharmacology with experimental validation, these findings provide a comprehensive understanding of THD's mechanisms in treating AS and offer a solid theoretical basis for its potential clinical application.

Background: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that results in the destruction of joints, connective tissues, muscle, tendons and fibrous tissue. Until now, there are no cure therapies. Objective: We aimed to assess the effectiveness of Tai Chi (TC) on RA patients by meta-analysis. Methods: The PubMed, Cochrane Library, EMBASE, web of science, China National Knowledge Infrastructure and Google Scholar were searched up to January 2023. We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) comparing TC to control conditions for RA patients. Review Manager (Version 5.3) software was used to analyze outcomes of time to walk 50 feet, joint tenderness, number of swollen joints or tender joints, handgrip strength, pain, the Health Assessment Questionnaire (HAQ) and withdraws overall. Results: A total of 351 patients with RA from six RCTs and three CCTs were included for meta-analysis. TC could also significantly decrease withdrawals overall in studies (OR = 0.28, 95% CI 0.12 to 0.67, p = 0.002). No significant treatment effects of physical function were identified of the other outcomes. Conclusion: Our findings indicated that TC was safe to RA patients, but it cannot improve physical function and pain. However, there is still lack of more evidence. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367498], identifier [CRD42022367498].

目的 探究活血通络法代表方桃红饮对动脉粥样硬化并发非酒精性脂肪肝炎小鼠肝组织炎症损伤和纤维化的影响.方法 野生型雄性C57/B6J小鼠10只为空白组,ApoE-/-/C57/B6J小鼠40只,随机分为模型组、阿托伐他汀组和中药治疗组(桃红饮高、中、低剂量组).模型组、阿托伐他汀组和中药治疗组给予西方高脂饮食造模12周,阿托伐他汀(5mg/kg)和中药组(11.54g/kg,5.77g/kg,2.89g/kg)以灌胃给药,空白组和模型组以灭菌纯水灌胃12周,检测血清ALT、AST、TRIG、TC、LDL,以及肝组织SOD、MDA和GSH水平;HE染色评估肝组织形态和炎性浸润、Masson染色评估肝组织纤维化程度、肝脏免疫荧光染色评估淋巴管数量和形态.结果 与模型组相比,干预组不同程度减低了血清TRIG、TC、LDL的水平(P＜0.05),增强了肝脏SOD、GSH的活性(P＜0.01),降低MDA(P＜0.01),减轻了肝脏脂肪变性及纤维化进展,其中高剂量组作用最为显著.结论 通过活血通络法代表方桃红饮治疗可以减缓动脉粥样硬化及并发的NAFLD进展,剂量与疗效显示正相关,这种作用可能与调控肝脏淋巴管生成途径有关.