Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To explore the effect and mechanism of hawthorn leaves flavonoids(HLF)on angiotensin Ⅱ(Ang Ⅱ)-induced myocardial hypertrophy.Methods The H9c2 cells were divided into control group(normal culture),model group(100 nmol·L-1 Ang Ⅱ for 24 h),experimental-L,-M,-H groups(received 100 nmol·L-1 Ang Ⅱ for 24 h,then treated with 25,50 and 100 mg·L-1 HLF for 24 h,respectively),anti-miR-NC and anti-miR-21a-5p groups(transfected with anti-miR-NC and anti-miR-21a-5p,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h),miR-NC+high-dose and miR-21a-5p+high-dose group(transfected with miR-NC and miR-21a-5p mimics,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h+100 mg·L-1 HLF for 24 h).The cell viability was detected by cell counting kit-8.The cell apoptosis was measured by flow cytometry.The expression levels of miR-21a-5p was assessed by quantitative real-time polymerase chain reaction.The expression levels of cyclooxygenase-2(COX2)and prostaglandin E2(PGE2)was measured by Western blot.Results The cell viabilities of control,model group experimental-H groups were 1.03±0.09,0.51±0.05 and 0.93±0.08;cell apoptosis rates were(7.69±0.61)％,(23.04±1.82)％and(9.43±0.71)％;the expression levels of miR-21a-5p were 1.00±0.09,2.43±0.18 and 1.09±0.08;the relative expression levels of COX2 protein were 0.42±0.03,0.85±0.08 and 0.40±0.04;the relative expression levels of PGE2 protein were 0.34±0.03,0.75±0.07 and 0.35±0.03;the differences of above indexes were statistically significant between the model group and the control and experimental-H groups(all P＜0.05).The cell viabilities of anti-miR-NC,anti-miR-21a-5p,miR-NC+high dose and miR-21a-5p+high dose groups were 0.52±0.04,1.12±0.08,0.94±0.09 and 0.57±0.04;the cell apoptosis rates were(23.04±1.82)％,(9.86±0.73)％,(9.47±0.64)％and(24.96±1.94)％;the expression levels of miR-21a-5p were 1.00±0.10,0.43±0.04,1.00±0.09 and 2.12±0.18;the relative expression levels of COX2 protein were 0.86±0.05,0.39±0.04,0.41±0.03 and 0.78±0.07;the relative expression levels of PGE2 protein were 0.74±0.06,0.38±0.07,0.36±0.02 and 0.71±0.05.Compared the anti-miR-21a-5p group with the anti-miR-NC group,compared the miR-21a-5p+high-dose group with the miR-NC+high-dose group,the differences of above indexes were statistically significant(all P＜0.05).Conclusion HLF can inhibit Ang Ⅱ-induced myocardial hypertrophy by regulating the expression of miR-21a-5p and COX2/PGE2 pathway.

The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Objective To observe the therapeutic effect and mechanism of Guhuaisi Kangfu Pills on rats with steroid-induced osteonecrosis of the femoral head(SONFH).Methods Sixty rats were randomly divided into blank group,model group,Xianling Gubao Capsules group and Guhuaisi Kangfu Pills low-,medium-and high-dose groups,10 rats in each group.Except for the blank group,the SONFH model was established by lipopolysaccharide combined with Glucocorticoid induction method in all other groups of rats.At the end of the intervention,for the femoral head,blood vessel radiography was performed to observe the microvascular changes in the bone marrow,and hematoxylin-eosin(HE)staining and calculation of the empty bone trap rate,Micro-CT scanning analysis,and compression experiments were carried out,and the real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the gene expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)1,vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule 1(CD31)in whole blood.Results Compared with the blank group,the blood supply in the femoral head medullary cavity of the model group was poor,the empty bone lacuna rate was increased(P＜0.05),the bone mineral density and bone volume fraction were significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were decreased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in whole blood were decreased(P＜0.05).Compared with the model group,the blood supply in the femoral head medullary cavity was relatively good,the empty bone lacuna rate was decreased(P＜0.05),the bone mineral density,bone volume fraction,trabecular number and trabecular thickness were significantly increased(P＜0.05),the trabecular separation was significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were increased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in the whole blood were increased(P＜0.05)in the high-dose group of Guhuaisi Kangfu Pills and Xianling Gubao Capsules group.There was no significant difference in the above indexes between the high-dose group of Guhuaisi Kangfu Pills and the Xianling Gubao Capsules group(P＞0.05).Conclusion Guhuaisi Kangfu Pills improves SONFH in rats,and its mechanism is related to the promotion of VEGF/PI3K/Akt pathway gene expression,thereby promoting angiogenesis.

Objective To develop effective measures to reduce antibiotic use duration in very low birth weight(VLBW)preterm infants in the neonatal intensive care unit through quality improvement methods.Methods The study population consisted of hospitalized VLBW preterm infants,with the percentage of hospitalization time during which antibiotics were used from November 2020 to June 2021 serving as the baseline.The specific quality improvement goal was to reduce the duration of antibiotic use.Factors affecting antibiotic use duration in preterm infants were analyzed using Pareto charts.Key drivers were identified,and specific interventions were formulated based on the stages of antibiotic use.Changes in the percentage of antibiotic use duration were monitored with run charts until the quality improvement target was achieved.Results From November 2020 to June 2021,the baseline antibiotic use duration percentage was 49%,with a quality improvement target to reduce this by 10%within 12 months.The Pareto analysis indicated that major factors influencing antibiotic duration included non-standard antibiotic use;delayed cessation of antibiotics when no infection evidence was present;prolonged central venous catheter placement;insufficient application of kangaroo care;and delayed progress in enteral nutrition.The interventions implemented included:(1)establishing sepsis evaluation and management standards;(2)educating medical staff on the rational use of antibiotics for preterm infants;(3)supervising the enforcement of antibiotic use standards during ward rounds;(4)for those without clear signs of infection and with negative blood cultures,discontinued the use of antibiotics 36 hours after initiation;(5)reducing the duration of central venous catheterization and parenteral nutrition to lower the risk of infection in preterm infants.The control chart showed that with continuous implementation of interventions,the percentage of antibiotic use duration was reduced from 49%to 32%,a statistically significant decrease.Conclusions The application of quality improvement tools based on statistical principles and process control may significantly reduce the antibiotic use duration in VLBW preterm infants.

Objective:Integrating genes and GEO database related cuproptosis chips,to analyze connection between cupropto-sis genes,immune infiltration and myocardial infarction(MI),construct risk prediction model,predict Western medicine and Chi-nese medicine,analyze miRNA-mRNA regulatory network,and to provides a new research direction for the future study of MI-related cuproptosis mechanism and immune infiltration.Methods:By GEO database retrieval of MI related chips,standardized processing and MI-related cuproptosis genes screening were performed,and immunoinfiltration analysis and quantification were performed based on the treated gene expression matrix,correlation between immune infiltrating cells and function was analyzed,as well as their differ-ences in MI group and the control group.Cuproptosis genes that most related to MI in immune infiltration were screened out,and the risk model was constructed to analyze the risk probability of cuproptosis genes in MI.The Enrichr website and Coremine Medical data-base were used to predict cuproptosis-related genes in MI in Western medicine and traditional Chinese medicine.Finally,the up-stream mirnas of FDX1 and SLC31A1 were predicted by miRTarBase,Starbase and Targetscan databases,and miRNA-mRNA regula-tory networks were constructed.Results:Correlation of immune infiltration showed that Tfh cells and B cells had the strongest positive correlation(r=0.68),while regulatory T cells and iDC had the strongest negative correlation(r=-0.63);the difference analysis of im-mune infiltration showed that the differences among mast cells,NK cells and Th1 cells in the MI group at the cellular level were the most significant(P<0.001);and the differences in APC co-inhibition and MHCⅠ at the functional level were the most significant(P<0.001).Six genes with the highest correlation between immune cells and immune function were screened out:ATP7A,DLD,FDX1,LIAS,LIPT1 and SLC31A1.Results of the risk model showed that the high levels of FDX1 and SLC31A1 were negatively correlated with the risk prediction of MI.A total of 21 Western medicines and 30 traditional medicines were predicted by database comparison.miRTarBase,Starbase and Targetscan databases predicted 9 upstream miRNAs of cuproptosis-related genes in MI,including has-miR-122-5p.Conclusion:Tfh cells,B cells,para-inflammatory,typeⅠinterferon response and other related immune cells and functions may play important roles in pathogenesis and prognosis of MI.FDX1 and SLC31A1 as the key genes of cuproptosis process,are negatively correlated with MI.A total of 30 kinds of traditional Chinese medicines including Spirulina,sheep liver,Wen ezhu,Pian jianghuang and Yujin may have potential value in treatment of MI.Finally,9 miRNAs including has-miR-122-5p may play an important role in the regulation of cuproptosis in myocardial infarction.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Aim To apply network pharmacology, molecular docking, and in vitro experimental techniques to predict as well as verify the antidepressant pharmacological mechanisms of Mengyao Anshen Buxin Liuwei pills. Methods TCMSP database and literature mining were used to obtain the active ingredients of Anshen Buxin six flavor pills , Swiss Target Prediction was applied to predict the ingredient related target information, and Cytoscape was employed to construct a medicinal herb ingredient target network. Depression targets were retrieved through GeneCards , Drugbank , OMIM and other databases. STRING database was used to obtain protein interaction relationship network information. DAVID database was used for GO biological process enrichment analysis and KEGG signaling pathway enrichment analysis. Autodock vina software was applied for molecular docking validation. In vitro injury model was established in BV2 microglial cells, cell viability was assessed by CCK-8 assay, and the mRNA expression of relevant core targets was assessed by qPCR. Results A total of 34 active components of Anshen Buxin Liuwei pills were screened, involving 140 potential targets and 59 core targets, involving 99 signaling pathways. Molecular docking results showed that betulinic acid, stigmasterol p-stiosterol 10 active components such as sitosterol and quercetin had good binding ability with AKT1, APP, ALB, MAPK3, VE GFA and MAPK 1 targets. The re suits in vitro showed that the activity of BV2 cells increased significantly compared with the model group. Anshen Buxin Liuwei pills could regulate the mRNA expression of each core target. Conclusion Anshen Buxin Liuwei pills may play an antidepressant role mainly through serotonin synaptic and other signaling pathways and related core targets.