Atherosclerosis is driven by metabolic dysregulation and endothelial dysfunction; however, the precise molecular mechanisms underlying its pathogenesis remain incompletely elucidated. Fibrinogen-like protein 1 (FGL1) is a well-established hepatokine with critical roles in regulating tumorigenesis and metabolic dysfunction, while its involvement in atherogenesis remains unclear. Our clinical and preclinical studies revealed elevated plasma FGL1 levels in atherosclerotic patients and mice, correlating with arterial stenosis severity. Prolonged high-fat diet exposure specifically upregulated hepatic FGL1 expression. Hepatic FGL1 overexpression accelerated atherosclerosis, while liver-specific knockdown reduced plaque burden. Exogenous administration of FGL1 accelerated endothelial injury and atherosclerosis progression. Mechanistically, liver-derived FGL1 accumulates in vascular endothelium through fibrinogen C-terminal domain Trp225-mediated binding to integrin β1's vWFA domain. This interaction promotes the conformational change of integrin β1 and the formation of integrin β1/ILK1 complex, co-activating FAK/ERK and Smad signaling to drive transcriptional reprogramming of endothelial cells. Therapeutic interventions targeting FGL1–integrin β1 axis by integrin β1 blocking antibody, FGL1-neutralizing antibody, or RGD peptide effectively attenuated endothelial injury and atherogenic progression in murine models. These findings establish hepatic FGL1 as a novel endocrine regulator of vascular pathophysiology, highlighting the FGL1–integrin β1 axis as a promising therapeutic target for endothelial protection and atherosclerosis management.

Black phosphorus is the most stable allotrope of phosphorus and possesses a unique layered structure. Black phosphorus nanosheets and black phosphorus quantum dots are the two main forms of black phosphorus nanomaterials (BPNM). BPNM hold significant application potential across various fields, yet a comprehensive evaluation of their biosafety, particularly the impact on hepatic metabolism, remains insufficient. This study investigates the hepatotoxic effects and mechanisms induced by BPNM, with a focus on lipid metabolic disorders. Following a 28-day daily oral administration of black phosphorus quantum dots or black phosphorus nanosheets at doses of 0.1 and 1 mg/kg, mice exhibited reduced insulin sensitivity, increased inflammatory responses, decreased serum levels of triglycerides and very-low-density lipoprotein (VLDL), and exacerbated hepatic lipid accumulation. RNA-sequencing revealed that oxidative stress is a key contributor to BPNM-induced metabolic disruption, accompanied by severe mitochondrial dysfunction. Similarly, BPNM exposure also elevated intracellular reactive oxygen species (ROS), impaired mitochondrial respiratory function and ATP production, consequently disrupted VLDL assembly and secretion in AML12 hepatocyte line. Moreover, ROS scavenger and ATP supplementation restored mitochondrial function and triglycerides transport in vitro. Findings demonstrate that BPNM promote hepatic lipid accumulation possibly by triggering oxidative stress and impairing mitochondrial function, thereby interfering with lipid transport, and resulting in hepatic lipid accumulation. This study highlights the potential metabolic disruption risks of BPNM and provides critical insights for their biosafety assessment and sustainable application.

Coronary heart disease (CHD), characterized by impaired coronary artery function, often results in myocardial ischemia, hypoxia, and necrosis, with clinical manifestations such as angina pectoris. Vascular smooth muscle cell (VSMC) hypercontraction, primarily regulated by intracellular calcium (Ca2+), plays a central role in pathological coronary vasoconstriction. This study aimed to evaluate the therapeutic effects of Huatuo Zaizao Pills (HTZZ) in alleviating myocardial ischemia caused by abnormal coronary artery contraction and to elucidate the underlying molecular mechanisms. A double-blind, multicenter, randomized, placebo-controlled clinical trial was conducted to assess the efficacy of HTZZ in patients with angina pectoris. In vivo, pituitrin-induced acute myocardial ischemia mice and spontaneously hypertensive rats (SHRs) were used to evaluate myocardial and vascular responses to HTZZ. In vitro, vasorelaxation mechanisms were investigated using isolated rat mesenteric arterial rings, patch clamp, calcium imaging, and [3H]-ryanodine binding assays. HTZZ significantly reduced the frequency and duration of angina attacks in clinical settings. It improved myocardial ischemia in mice and enhanced vascular elasticity and diastolic function in SHRs. Mechanistically, HTZZ induced vasodilation by inhibiting extracellular Ca2+ influx and reducing intracellular Ca2+ levels via suppression of L-type calcium channels (LTCCs) and ryanodine receptors (RyRs). Long-term HTZZ administration also downregulated LTCC expression at both the protein and mRNA levels. HTZZ effectively alleviates angina and myocardial ischemia by suppressing Ca2+-mediated vasoconstriction through targeting LTCCs and RyRs. These findings highlight HTZZ as a promising therapeutic candidate for CHD characterized by coronary vasospasm and ischemia.

Alterations in liver metabolism play a pivotal role in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Asprosin is reported to be released from white adipose tissue during fasting and targets the liver. However, the role of asprosin, especially from organs other than adipose tissue, in MASLD remains poorly understood. These findings demonstrate that plasma asprosin levels are significantly elevated in MASLD patients and animal models. Additionally, asprosin expression increased in the liver of MASLD mice. Hepatocyte-specific overexpression of asprosin impairs mitochondrial fatty acid β-oxidation (FAO), whereas its knockdown not only enhances FAO in mice but also compensates for fenofibrate's limitations in MASLD treatment. Mechanistic investigations reveal that the interaction of asprosin with FABP5 facilitates its abnormal nuclear localization, and asprosin directly bound to and inhibites peroxisome proliferator-activated receptor elements (PPREs), which negatively regulated PPARα transcriptional activity, and disrupts hepatic FAO pathways. GalNAc-siRNAs targeting hepatic FABP5 ameliorate hepatic steatosis. These findings reveal that the secretory adipose factor asprosin is expected to act as a biological marker for early clinical diagnosis and prognostic evaluation of MASLD. Moreover, targeting hepatic asprosin gene inhibition and GalNAc-siRNAs to inhibit hepatic FABP5 both offer potential therapeutic benefits in the treatment of MASLD.

To investigate the effects of “Shengjiang Powder”, a representative formula for “simultaneous treatment of liver and heart,” on liver tissue inflammation and fibrosis in mice with atherosclerosis(AS) concurrent with non-alcoholic fatty liver disease (NAFLD). Ten wild-type male C57/B6J mice were assigned to the control group, and 40 ApoE -/- mouse were randomly divided into the model group, atorvastatin group, and traditional Chinese medicine (TCM) treatment groups. The model group, atorvastatin group, and TCM treatment groups were fed a high-fat Western diet for 12 weeks. Atorvastatin and TCM groups were administered via gavage, while the control group and model group received sterile purified water via gavage for 12 weeks. Serum levels of ALT, AST, TRIG, TC, LDL, as well as liver tissue levels of SOD, MDA, and GSH were measured. HE staining was used to evaluate liver tissue morphology and inflammatory infiltration. Western blot was used to detect the effect of Shengjiang Powder on the activation of AMPK/mTOR signaling pathway. Network pharmacology analysis was performed beforehand to identify potential targets of Shengjiang Powder in regulating fatty liver and atherosclerosis, with AMPK identified as a key target. Compared with the model group, the Shengjiang Powder treatment reduced serum levels of TRIG, TC, and LDL (P < 0.05), increased liver SOD and GSH activity (P < 0.01), decreased MDA (P < 0.01), alleviated liver steatosis, reduces the area of aortic sinus plaques, improved hepatic steatosis and inflammation, inhibited the expression of inflammatory factors and activated the AMPK/mTOR signaling pathway, consistent with the network pharmacology prediction that AMPK is a critical regulatory target. Treatment with “Shengjiang Powder,” a representative formula for “simultaneous treatment of liver and heart,” can slow the progression of atherosclerosis and concurrent NAFLD. The dosage shows a positive correlation with efficacy, and this effect is related to the regulation of liver oxidative stress and inflammation-induced fibrosis pathways.

Chronic heart failure(HF) has become a disease of global concern due to its high morbidity and mortality.This has highlighted the need for cardioprotective agents.The Tonifying Kidney and Activating Blood(KTBA) decoction has been approved for clinical treatment of chronic HF.Tanshinone IIA(Tan IIA), rooted from Salvia miltiorrhiza of KTBA, has been approved for treating cardiovascular conditions.However, the mechanism is still unclear.This study examined the impact of KTBA on cardiomyocyte fibrosis in a rat model of heart failure post-myocardial infarction, induced by ligation of the left anterior descending coronary artery, followed by exhaustive swimming and starvation. Additionally, the effects of Tan IIA on CCD-841CoN cells were assessed under ischemic conditions in a 37 °C incubator with hypoxic environment (1% O2, 5% CO2, and 94% N2). The investigation employed an integrative approach combining network pharmacology with molecular mechanism analysis.The findings of network pharmacology indicate that KTBA may exert its influence by targeting key proteins such as TNF, AKT1, STAT3, RELA (NF-κB p65), NFκBIA (I-κBα), and MAPK14 (p38α).Results showed that KTBA increased SERCA2a level, lowered collagen I and III, α-SMA, and phospholamban levels, reduced collagen fiber deposition, and delayed mitochondria injury.This cardioprotection effect was perhaps due to suppressing the expressions of p38MAPK, I-κBα, NF-κB, AQP4,AKT, PI3K, TNF-α, and STAT3 and increasing the levels of ZO-1 and Occludin in hippocampus of chronic HF rats, which were partially diminished by SB203580 and PDTC.Additionally, Tan IIA reduced levels of p38MAPK, I-κBα, NF-κB, STAT3, and increased levels of AQP4, Claudin-1, ZO-1, and ZO-2,that were reduced by siRNAs targeting p38MAPK, NF-κB, and AQP4.In conclusion, by modulating the p38MAPK/NF-κB/AQP4 axis, KTBA decoction delays cardiomyocyte fibrosis through alleviating hippocampal blood-brain barrier and Tan IIA improves enterocyte barrier integrity.

Objective:This study aims to summarize all single clinical studies of Guanxin Shutong (GXST) capsule combined with Western medicine in the treatment of coronary heart disease angina pectoris and to systematically evaluate its efficacy and safety. Methods:This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Chinese and English databases were searched to collect the randomized controlled trials (RCTs) of GXST capsule combined with conventional Western medicine in the treatment of patients with angina pectoris of coronary heart disease and to extract the data. Cochrane Risk of Bias Tool was used to evaluate literature quality, and RevMan5.3 software was used to evaluate the outcome indicators, such as total effective rate of angina pectoris, frequency of angina pectoris, duration of angina pectoris, total effective rate of electrocardiogram (ECG), lipid level, inflammatory factor level, hemorheology, cardiac function, and adverse reactions, and to assess publication bias. Results:A total of 27 RCTs with 3440 cases were identified. The results showed that the combined use of GXST capsule was more effective in terms of total effective rate of angina pectoris, frequency of angina pectoris, duration of angina pectoris, and total effective rate of ECG. In addition, the combined use of GXST capsule had more advantages in reducing total cholesterol, low-density lipoprotein cholesterol, interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein, and whole-blood viscosity and increasing left ventricular ejection fraction and high-density lipoprotein cholesterol. However, for triglyceride and interleukin-1, there were two different results before and after the sensitivity analysis, which were attributed to the quality of the included literature. In terms of plasma viscosity and adverse reactions, after excluding the literature with large heterogeneity, sensitivity analysis indicated that the combined use of GXST capsule was helpful to reduce plasma viscosity and adverse reactions. Conclusions:GXST capsule combined with conventional Western medicine has better efficacy and safety in the treatment of angina pectoris of coronary heart disease compared with Western medicine alone. However, our study still has some limitations. Thus, more standardized RCTs are needed in future studies to verify the conclusions, and longer follow-up periods need to be designed to explore the long-term efficacy.

BackgroundZhigancao Decoction (ZGCD) is derived from “Treatise on Febrile Diseases” and is traditionally prescribed for treating a variety of cardiovascular conditions. As of now, there are no data to support its use as a treatment for diabetic cardiomyopathy (DCM) and the mechanism behind the effect is unclear as well. In the present study, clinical evidence for the efficacy of ZGCD in patients with DCM was examined using a meta-analysis and its underlying anti-DCM molecular mechanisms were explored via network pharmacology.MethodsThe current study utilized an extensive search strategy encompassing various domestic and foreign databases databases to retrieve pertinent articles published up to June 2024. In light of this, a thorough evaluation of the benefits and safety of Zhigancao decoction (ZGCD) was conducted in this study using RevMan and Stata. Subsequently, a number of active compounds and target genes for ZGCD were gathered from the TCMSP and BATMAN-TCM databases, while the main targets for DCM were obtained from databases such as GenCards, OMIM, TTD, and DrugBank. To select core genes, protein-protein interaction networks were generated using the STRING platform, and enrichment analyses were completed using the Metascape platform.ResultsMeta-analysis results were ultimately derived from 9 studies involving 661 patients in total. In comparison with WM therapy alone, the pooled results showed that ZGCD significantly enhanced overall effectiveness. Additionally, the utilization of ZGCD was leading to a reduction in LVEDV, LVESV and LVDD, also a greater increase in LVEF. Meanwhile, the utilization of ZGCD during intervention was more effective in reducing SBP, and DBP. In addition, the ZGCD showed potential in reducing the occurrence of adverse events. In the context of network pharmacology, five constituents of ZGCD—namely lysine, quercetin, gamma-aminobutyric acid, stigmasterol, and beta-sitosterol—are posited to exert anti-diabetic cardiomyopathy (anti-DCM) effects through interactions with the molecular targets ASS1, SERPINE1, CACNA2D1, AVP, APOB, ICAM1, EGFR, TNNC1, F2, F10, IGF1, TNNI2, CAV1, INSR, and INS. The primary mechanisms by which ZGCD may achieve its anti-DCM effects are likely mediated via the AGEs/RAGE signaling pathway, as well as through pathways related to lipid metabolism and atherosclerosis.ConclusionIn comparison to WM therapy alone, ZGCD demonstrates greater efficacy and safety in the management of DCM. ZGCD not only significantly reduces blood pressure, but also enhances cardiac function while producing fewer adverse effects. The therapeutic effects of ZGCD on DCM can likely be ascribed to its capacity to modulate the AGEs-RAGE signaling pathway, as well as its efficacy in enhancing lipid metabolism and mitigating atherosclerosis.Systematic Review Registrationidentifier (INPLASY202430133).

Background Jianpi Qutan Fang (JPQT) is a Chinese herbal medicine formulation containing 8 Traditional Chinese Medicine (TCM) components.The key target and potential drug mechanism of JPQT for unstable angina (UA) and Unstable angina syndrome of spleen deficiency and phlegm turbidity(UA-PXTZ) were determined by network pharmacology, RNA sequencing (RNA-seq) and molecular docking methods. Methods JPQT targets were retrieved from public databases. The related targets of UA and UA-PXTZ were obtained from the database and RNA-seq data set. Then the potential targets of JPQT and UA, JPQT and UA-PXTZ were verified. The hub targets and signaling pathways were obtained by bioinformatics analysis.Molecular docking was performed to predict the binding of JPQT to UA core targets and JPQT to hub targets. Results A total of 2146 UA-related therapeutic targets were identified. A total of 193 effective compounds and 269 target proteins were identified in the 8 traditional Chinese medicines of JPQT. Among them, 187 proteins were identified as targets for JPQT in the treatment of UA. RNA-seq identified 210 differential genes specific to spleen deficiency and phlegm turbidity syndrome, of which 118 were up-regulated and 92 were down-regulated in UA spleen deficiency and phlegm turbidity syndrome.There are 8 DEGs that overlap with the 187 therapeutic targets of JPQT for UA mentioned above. These 8 DEGs may be the core targets of JPQT in the treatment of UA with spleen deficiency and phlegm turbidity syndrome. Eight DEGs overlapped with two of the 43 core targets, MMP9 and PPARG. Five core targets with the most connections in the PPI network of UA were selected, including AKT1, IL-6, STAT3, TP53 and JUN, and two hub targets MMP9 and PPARG of spleen deficiency and phlegm turbidity syndrome were molecularly docked. The results showed that the above seven target proteins had therapeutic effects, and the binding ability of isorhamnetin and stigmasterol was stronger than that of the other three active components. Conclusion This study revealed the potential therapeutic effect of JPQT on UA, especially on UA-PXTZ, and provided a theoretical basis for exploring the potential therapeutic mechanism of JPQT on UA.

Ethnopharmacological relevance: Myocardial infarction has likely contributed to the increased prevalence of heart failure(HF).As a result of ventricular remodeling and reduced cardiac function, colonic blood flow decreases, causing mucosal ischemia and hypoxia of the villous structure of the intestinal wall.This damage in gut barrier function increases bowel wall permeability, leading to fluid metabolism disorder,gut microbial dysbiosis, increased gut bacteria translocation into the circulatory system and increased circulating endotoxins, thus promoting a typical inflammatory state.Traditional Chinese Medicine plays a key role in the prevention and treatment of HF.Kidney-tonifying Blood-activating(KTBA) decoction has been proved for clinical treatment of chronic HF.However,the mechanism of KTBA decoction on chronic HF is still unclear. Aims of the study: The effect of KTBA decoction on gut microbiota and metabolites and p38MAPK/p65NF- kappa B/ AQP4 signaling in rat colon was studied to investigate the mechanism that KTBA decoction delays ventricular remodeling and regulates water metabolism disorder in rats with HF after myocardial infarction based on the theory of "Kidney Storing Essence and Conducting Water". Material and methods: In vivo,a rat model of HF after myocardial infarction was prepared by ligating the left anterior descending coronary artery combined with exhaustive swimming and starvation.The successful modeling rats were randomly divided into five groups:model group, tolvaptan group(gavaged 1.35mg/(kg center dot D) tolvaptan),KTBA decoction group(gavaged 15.75g/(kg center dot D) of KTBA decoction),KTBA decoction combined with SB203580(p38MAPK inhibitor) group(gavaged 15.75g/(kg center dot D) of KTBA decoction and intraperitoneally injected 1.5mg/(kg center dot D) of SB203580),and KTBA decoction combined with PDTC(p65NF-kB inhibitor) group(gavaged 15.75g/(kg center dot D) of KTBA decoction and intraperitoneally injected 120mg/(kg center dot D) of PDTC).The sham-operation group and model group were gavaged equal volume of normal saline.After 4 weeks of intervention with KTBA decoction,the effect of KTBA decoction on the cardiac structure and function of chronic HF model rats was observed by ultrasonic cardiogram.General state and cardiac index in rats were evaluated.Enzyme linked immunosorbent assay(ELISA) was used to measure N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in rat serum.Hematoxylin and eosin(H & E) staining,and transmission electron microscope(TEM) were used to observe the morphology and ultrastructure of myocardial and colonic tissue,and myocardial fibrosis was measured by Masson ' s staining.Cardiac E-cadherin level was detected by Western blot.The mRNA expression and protein expression levels of p38MAPK,I- kappa B alpha , p65NF- kappa B,AQP4,Occludin and ZO -1 in colonic tissue were detected by reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR) and immunohistochemistry. Protein expression of p38MAPK, p-p38MAPK,I- kappa B alpha ,p-I- kappa B alpha ,p65NF- kappa B, p-p65NF- kappa B,AQP4,Occludin and ZO -1 in rat colon was detected using Western blot.Colonic microbiota and serum metabolites were respectively analyzed by amplicon sequencing and liquid chromatography -mass spectrometry.In vitro, CCD-841CoN cell was placed in the ischemic solution under hypoxic conditions (94%N 2 ,5%CO 2 ,and 1%O 2 ) in a 37 degrees C incubator to establish an ischemia and hypoxia model. The CCD-841CoN cells were divided into 7 groups, namely blank group and model group with normal rat serum plus control siRNA, tolvaptan group with rat serum containing tolvaptan plus control siRNA, KTBA group with rat serum containing KTBA plus control siRNA, KTBA plus p38MAPK siRNA group, KTBA plus p65NF- kappa B siRNA group,and KTBA plus AQP4siRNA group.After 24h and 48h of intervention with KTBA decoction,RT-qPCR,immunofluorescence and Western blot was used to detect the mRNA expression and protein expression levels of p38MAPK,I- kappa B alpha ,p65NF- kappa B,AQP4, Occludin and ZO-1 in CCD-841CoN cells. Results: Compared with the model, KTBA decoction improved the general state, decraesed the serum NT-proBNP level,HW/BW ratio, LVIDd and LVIDs, increased E-cadherin level,EF and FS,reduced number of collagen fibers deposited in the myocardial interstitium,and recovered irregular arrangement of myofibril and swollen or vacuolated mitochondria with broken crista in myocardium.Moreover, KTBA decoction inhibited the expression of p38MAPK,I- kappa B alpha ,and p65NF- kappa B and upregulated AQP4, Occludin and ZO-1 in colon tissues and CCD-841CoN cells.Additionally,p38siRNA or SB203580, p65siRNA or PDTC, and AQP4siRNA partially weakened the protective effects of KTBA in vitro and vivo.Notably,The LEfSe analysis results showed that there were six gut biomaker bacteria in model group, including Allobaculum, Bacillales,Turicibacter, Turicibacterales,Turicibacteraceae,and Bacilli. Besides, three gut biomaker bacteria containing Deltaproteobacteria, Desulfovibrionaceae,and Desulfovibrionales were enriched by KTBA treatment in chronic HF model.There were five differential metabolites, including L-Leucine,Pelargonic acid, Capsidiol,beta-Carotene,and L- Erythrulose, which can be regulated back in the same changed metabolic routes by the intervention of KTBA.L-Leucine had the positive correlation with Bacillales, Turicibacterales,Turicibacteraceae,and Turicibacter.L-Leucine significantly impacts Protein digestion and absorption, Mineral absorption,and Central carbon metabolism in cancer regulated by KTBA, which is involved in the expression of MAPK and tight junction in intestinal epithelial cells . Conclusions: KTBA decoction manipulates the expression of several key proteins in the p38MAPK/p65NF- kappa B/ AQP4 signaling pathway, modulates gut microbiota and metabolites toward a more favorable profile, improves gut barrier function, delays cardiomyocyte hypertrophy and fibrosis,and improves cardiac function.

IntroductionThe single and combined association between brominated flame retardants (BFRs) and cardiovascular diseases (CVD) has remained unelucidated. This research aimed at exploring the associations between mixture of BFRs and CVD.MethodsThis research encompassed adult participants from the National Health and Nutrition Examination Survey in 2005–2016. The weighted quantile sum (WQS) model and quantile g-computation (QGC) model were applied to examine the combined effects of BFRs mixture on CVD.ResultsIn this research, overall 7,032 individuals were included. In comparison with the lowest quartile, the highest quartile of PBB153 showed a positive association with CVD, with odds ratio (OR) values and 95% confidence intervals (CI) of 19.2 (10.9, 34.0). Furthermore, the acquired data indicated that PBB153 (OR: 1.23; 95% CI: 1.02, 1.49), PBB99 (OR: 1.29; 95% CI: 1.06, 1.58), and PBB154 (OR: 1.29; 95% CI: 1.02, 1.63) were linked to congestive heart failure. PBB153 was also related to coronary heart disease (OR: 1.29; 95% CI: 1.06, 1.56). Additionally, a positive correlation between the BFRs mixture and CVD (positive model: OR: 1.23; 95% CI: 1.03, 1.47) was observed in the weighted quantile sum (WQS) model and the quantile g-computation (QGC) model.DiscussionTherefore, exposure to BFRs has been observed to heighten the risk of cardiovascular disease in US adults, particularly in the case of PBB153. Further investigation is warranted through a large-scale cohort study to validate and strengthen these findings.

Recent trends suggest that Chinese herbal medicine formulas (CHM formulas) are promising treatments for complex diseases. To characterize the precise syndromes, precise diseases and precise targets of the precise targets between complex diseases and CHM formulas, we developed an artificial intelligence-based quantitative predictive algorithm (DeepTCM). DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling, molecular and theoretical levels of traditional Chinese medicine (TCM). As an example, our model simulated the optimal CHM formulas for the treatment of coronary heart disease (CHD) with depression, and through model sensitivity analysis, we calculated the balanced scoring of the formulas. Furthermore, we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions. Finally, we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice. This novel multiscale model opened up a new avenue to combine “disease syndrome” and "macro micro" system modeling to facilitate translational research in CHM formulas.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe−/− mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.

目的:探讨冠心舒通胶囊用于冠心病心力衰竭心血瘀阻证患者的临床疗效.方法:研究选取2020年6月至2022年8月就诊于辽宁中医药大学附属医院专家门诊并被诊断为冠心病心力衰竭心血瘀阻证的患者98例.将98例患者采用随机表法分为对照组、观察组各49例,两组患者均根据指南采用冠心病心力衰竭规范化治疗,观察组在此基础上加用中成药冠心舒通胶囊,对比两组治疗前后心脏结构功能指标、症状疗效总有效率、运动耐力、心率变异性、生活质量、炎症因子水平.结果:治疗前,两组患者在超敏C反应蛋白(hs-CRP)、6min步行试验(6MWT)、明尼苏达心力衰竭生活质量量表(MLHFQ)、左室射血分数(LVEF)、肿瘤坏死因子-α(TNF-α)、左室舒张末内径(LVEDD)、N-末端B型脑钠肽前体(NT-proBNP)、心率变异性(HRV)方面对比差异无统计学意义,资料具有可比性.治疗后,与对照组比较,观察组患者中医证候有效率(Z=-2.362,P＜0.05)及美国纽约心脏病协会(NYHA)心功能分级有效率(Z=-2.175,P＜0.05)均优于对照组,差异具有统计学意义.与本组治疗前比较,两组患者治疗后MLHFQ、LVEDD、TNF-α、NT-proBNP、hs-CRP水平均明显降低(P＜0.05,P＜0.01);与对照组治疗后比较,观察组患者改善更明显(P＜0.05,P＜0.01).与本组治疗前比较,两组患者治疗后6MWT、LVEF、HRV均显著升高(P＜0.01);与对照组治疗后比较,观察组患者改善更显著(P＜0.01).结论:冠心舒通胶囊联合规范化治疗能够改善慢性心力衰竭心血瘀阻证患者的躯体症状,提高患者的运动耐量及生活质量,减轻炎症反应,提高心率变异性,改善心脏结构和功能.

代谢相关脂肪性肝病多合并冠脉血管损伤,属于中医"肝心同病"范畴,病因病机为"肝失敷和、心脉痹阻".近年来,外泌体调控"肝脏-血管"通讯干预代谢相关脂肪性肝病患者冠脉血管损伤逐渐成为研究热点,肝细胞源性外泌体可携载miR-NA与冠脉血管内皮细胞结合,调控内皮通透性,并介导下游炎性因子表达增加,与中医"肝心同病"病理过程有诸多相似之处.在"肝心同治"理论的指导下,从外泌体及其携载miR-1 介导"肝脏-血管"角度出发,分析"肝失敷和,心脉痹阻"对代谢相关脂肪性肝病患者冠脉血管损伤的分子生物学作用机制,揭示"肝心同治"的效应机制,为"肝心同治"理论的现代化解读提供了新思路,未来有望靶向干预外泌体的功能,实现疾病的精准靶向干预.

目的 探究补肾活血复方对慢性心衰(CHF)大鼠肠道水液代谢与结肠核因子-κB(NF-κB)、闭合蛋白(Occludin)的相关性影响.方法 将60只SD雄性大鼠随机分为空白组15只和实验组45只.实验组大鼠通过结扎冠脉左前降支联合力竭式游泳、饥饿,建立慢性心衰模型.成模的大鼠随机分3组,即模型组、托伐普坦组及补肾活血组.托伐普坦组灌胃托伐普坦混悬液1.35mg/(kg·d),补肾活血组灌胃补肾活血中药汤剂15.75g/(kg·d),空白组和模型组灌胃等体积蒸馏水.灌胃28日后,采用酶联免疫法(ELISA)检测大鼠血清氨基末端脑钠肽前体(NT-proBNP),心脏彩超检测大鼠左心室结构与功能,免疫印迹法(Western blotting)检测大鼠结肠组织NF-KB、Occludin蛋白表达,苏木素-伊红(HE)染色观察大鼠心肌与结肠组织.结果 与空白组比较,模型组大鼠LVEdd、LVEsd、NT-proBNP升高,LVEF、LVFS降低,结肠组织NF-κB蛋白表达升高,Occludin蛋白表达降低(P＜0.05).与模型组比较,补肾活血组大鼠LVEdd、LVEsd、NT-proBNP降低,LVEF、LVFS升高,结肠组织NF-κB蛋白表达降低,Occludin蛋白表达升高(P＜0.05).结论 补肾活血复方可能通过下调CHF大鼠结肠组织NF-κB蛋白表达,上调紧密连接蛋白Occludin表达,改善肠黏膜屏障损伤,调节水液代谢紊乱,起到治疗CHF作用.

OBJECTIVE:To investiage the possible mechanism underlying the effect of the Jianpi Qutan Fang (, JPQT) on Atherosclerosis (AS) which is the main pathological process of most cardiovascular diseases that affect millions of adults worldwide.METHODS:In the present study, rats were fed with a high-fat-diet (HFD) with vitamin D3 for 16 weeks and were orally administered atorvastatin treatment and different doses of JPQT. Histopathological changes and ultrastructural changes in the aorta were evaluated through hematoxylin-eosin staining and transmission electron microscopy (TEM), respectively. Suppressor of cytokine signaling 1 (SOCS1)/Janus kinase 1 (JAK1)/ signal transducer and activator of transcription 1 (STAT1) signaling pathways were detected through Western blotting.RESULTS:JPQT treatment decreased the lipid levels of triglyceride, low-density lipoprotein, and cholesterol, the inflammatory cytokine levels of interleukin 1 beta (IL-1β), IL-6 and IL-8 in rat serum, but increased high-density lipoprotein and IL-10 serum levels. JPQT treatment ameliorated pathological changes in the aorta of AS model rats. Moreover, JPQT upregulated SOCS1 protein expression and down-regulated phosphorylated protein expression levels of p-JAK1 and p-STAT1.CONCLUSION:These results suggest that JPQT induces anti-atherosclerosis effects through anti-inflammatory and inhibiting JAK/STAT signaling pathways in HFD fed rats.

胸痹与西医学所指的冠状动脉粥样硬化性心脏病关系密切,以胸部闷痛、甚则胸痛彻背,喘息不得卧为主要临床表现,并伴有潜伏期较长,发病较为急骤,治疗周期长的特点,根据《中国心血管健康与疾病报告2020》显示其患病率呈逐年增高、患病人群也有从老年人群向年轻人群转变的趋势,已成为危害我国公共健康和制约经济发展的重要疾病之一.中医"胸痹"病名起源于《黄帝内经》,经历代医家不断充实、发展日趋完善,现今普遍认同张仲景在《金匮要略》所提出"阳微阴弦"的观点,认为此病虽病位在心但根据中医五脏相关理论认为胸痹可为多脏同病,胸痹成因与肝之疏泄、脾之转运、肾之蛰藏功能都密切相关,临证可将其分为:气血不足、肾虚血瘀、痰瘀互结、感受外邪等几个方面,治以祛邪益气、活血化瘀、豁痰祛浊等法.本文将对国医大师从肝、脾、肾论治胸痹进行探索,突出国医大师在辨证、选方、用药、预防调摄等方面的见解,总结国医大师宝贵的学术思想和治疗经验,以期为临床论治胸痹提供重要参考和理论依据.

冠心病患者经历经皮冠状动脉介入(PCI)手术之后,病机发生微妙变化,术后体虚,瘀血久滞,情郁气结,易化热生毒,甚至形成瘀毒郁结的重症,诱发术后心绞痛、术后再狭窄、术后抑郁焦虑等并发症.根据其瘀毒郁结的病机特点,参考《黄帝内经》"火郁发之""结者散之"的理论,当结合中医"发散法"治之.文章将探讨"发散法"的理论内涵和用药特点.在PCI术后胸痹治疗中以"发散法"为纲,结合"发散郁火、通阳散结、升阳散火"等治法,加入理气散瘀、疏风散热、解毒散结之中药,使瘀血、热毒、情郁得解,进而缓解PCI术后胸痛再发等情况,为PCI术后胸痹治疗提供了新思路.