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.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Intestinal flora imbalance and abnormal glucose and lipid metabolism are important risk factors and pathological mechanisms of colorectal polyps. "Spleen deficiency and dampness accumulation" is the core pathogenesis of colorectal polyps. The imbalance of intestinal flora is related to spleen deficiency, and the application of Chinese herbs for invigorating spleen is helpful to the recovery of intestinal flora balance. Abnormal glucose and lipid metabolism is related to dampness accumulation, and it is effective to treat it with bitter and spicy herbs or spleen-invigorating and dampness-eliminating herbs. The interaction between intestinal flora imbalance and abnormal glucose and lipid metabolism changes intestinal microenvironment, damages intestinal epithelial cells, causes abnormal proliferation of intestinal stem cells and leads to colorectal polyps, which is consistent with the pathogenesis of spleen deficiency and dampness accumulation in Traditional Chinese Medicine. Thus, we tried to explore the biological connotation of the pathogenesis of "spleen deficiency and dampness accumulation" of colorectal polyps from the perspective of the interaction of intestinal flora and glucose and lipid metabolism, in order to provide reference for identifying high-risk population and analyzing the therapeutic mechanism of compound prescription for invigorating spleen and removing dampness.

Objective The objective of this study was to investigate the expression and clinical significance of serum miR-NA-24(miR-24)and miRNA-509(miR-509)in patients with hepatocellular carcinoma(HCC).Methods Ninety-four HCC patients(HCC group)who visited Suining Central Hospital in Sichuan province from January 2019 to October 2020 were select-ed,and 90 healthy subjects(control group)who underwent the physical examination center at the same time were selected.The ex-pression of miR-24 and miR-509 in human liver cancer cell lines and the serum of participants in the two groups was detected by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation between miR-24 and miR-509 levels and the clinicopathological characteristics and prognosis of HCC was analyzed.Results The expression of miR-24 in the serum of HCC pa-tients was significantly higher than that of the control group(3.19±0.29vs.0.66±0.20),(t=-68.601,P＜0.01),and the ex-pression of miR-509 was significantly lower than that of the control group(0.74±0.27 vs.1.24±0.28),(t=12.331,P＜0.01).The expression of miR-24 in serum was positively correlated with alpha fetoprotein(AFP)level,metastasis,and TNM stage(r=0.821,0.510,0.762,P＜0.01),and negatively correlated with the degree of differentiation(r=-0.771,P＜0.01).The expression of miR-509 in serum was negatively correlated with AFP level,metastasis and TNM stage(r=-0.820,-0.506,-0.766,P＜0.01),and negatively correlated with the degree of differentiation(r=0.775,P＜0.01).Conclusion The expression of serum mir-24 is up-regulated in HCC patients,while the expression of serum mir-509 is down-regulated.Both of them are closely related to HCC metastasis and malignancy.Clinical testing of serum miR-24 and miR-509 levels in patients can help diagnose and evaluate the condition of HCC.

Objective:To analyze the prescriptions for the treatment for epigastric pain in A Hundred Years of Traditional Chinese Medicine Clinicians in China. Methods:The clinical medical records of well-known TCM doctors for the treatment of epigastric pain were included in the A Hundred Years of Traditional Chinese Medicine Clinicians in China. The database of clinical prescriptions and medicines was built, and the ancient and the Ancient and Modern Medical Records Cloud Platform (V 2.1) was applied and the evaluation of drug efficacy, sex, taste, and menstruation were conducted. Descriptive analysis, association rules, hierarchical clustering, and complex network analysis were applied in the rule of medication, drug pairs and core prescriptions. Results:Data was cleaned according to the inclusion and exclusion criteria, and 270 prescriptions were collected, involving 265 kinds of drugs, and the cumulative frequency of drug use was 3 249. The analysis showed that the drugs commonly used by famous traditional Chinese medicine doctors for the treatment of epigastric pain were mainly warm drugs, tast-balance drugs, and mildly cold drugs. The main flavors of medicines were pungent medicines, bitter medicines, sweet medicines, and effects were mainly drugs that regulate qi, clear heat, and invigorate the spleen. The frequency of drug meridians mainly belonged to spleen meridian, stomach meridian, lung meridian, liver meridian, heart meridian. The effects of the drug were mainly to dry dampness, reduce side effects, regulate qi, clear heat, invigorate spleen, and soften liver and analgesics. Association rule analysis found that the commonly used drug pairs were Pinellia- Tangerine Peel, Atractylodes Macrocephala- Poria, Poria- Tangerine Peel, Atractylodes- Tangerine Peel, Amomum tangerine Peel, Ochre- generation- Inula, Rhizoma Coptis- Evodia, and so on. Cluster analysis showed that Liujunzi Decoction, Zuojin Pill, and Shaoyao Gancao Decoction were mainly used. The drug complex network diagram showed that the core prescription of the drug is Xiangsha Liujunzi Decoction. Conclusion:The well-known TCM doctor focuses on strengthening the spleen and regulating qi, reconciling qi and blood, The treatment identified that the mutual warming and clearing, tonifying and deoppilation, and neutral are the main principles.

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.
Aged ; Altitude ; Altitude Sickness/genetics* ; Case-Control Studies ; China ; Familial Primary Pulmonary Hypertension/genetics* ; Humans ; Hydroxamic Acids/therapeutic use* ; Hypertension, Pulmonary/genetics* ; Inflammation ; Leukocytes, Mononuclear/pathology* ; Male ; Middle Aged ; Transcription Factors ; Transcriptome/genetics* ; Vorinostat/therapeutic use*

In this study, liquid chromatography-mass spectrometry(LC-MS) and high performance liquid chromatography(HPLC) were employed for qualitative and quantitative analysis of the steroidal saponins in rhizomes of Paris polyphylla var. yunnanensis from three different habitats cultured in vitro, in an attempt to explore whether the rhizomes of the medicinal herb cultured in vitro can synthesize the steroidal saponins, including polyphyllinsⅠ, Ⅱ, and Ⅶ, the quality markers specified in Chinese Pharmacopoeia(2020 edition). A total of 20 steroidal saponins were identified in the rhizomes from Changxin, Yunlong(S1), Fengyi, Dali(S2), and Niujie, Eryuan(S3): parisyunnanoside A and parisyunnanoside D or E, proto-polyphyllin Ⅱ, polyphyllins G and H, polyphyllinsⅠ, Ⅱ, Ⅴ, Ⅵ, and Ⅶ, dioscin, gracillin, prosapogenin A, Tg, isomer of Th, saponin Th, reclinatoside, proto-pairs D, pseudoproto-dioscin, and 23-O-glc-(23S,25R)-spirost-5-en-3β,23α,27-triol-3-O-rha-(1→2)-[ara(1→4)]-glc or 27-O-glc-(23S,25R)-spirost-5-en-3β,27α-diol-3-O-rha-(1→2)-[ara(1→4)]-glc. Among them, polyphyllinsⅠ, Ⅱ, and Ⅶ were detected in the rhizomes from S1, with the mass fraction of 0.109 1%, 0.165 2%, and 0.051 03%, respectively(total 0.325 3%). Polyphyllins Ⅱ and Ⅶ were identified in the rhizomes from S2 with the respective mass fraction of 0.192 2% and 0.074 23% and total content of 0.266 5%. Moreover, polyphyllins Ⅱ and Ⅶ were also found in the rhizomes from S3, which had the mass fraction of 0.207 7% and 0.186 9%, separately, with the total content of 0.394 6%. Thus, steroidal saponins, including the quality makers polyphyllins Ⅰ, Ⅱ, and Ⅶ recorded in Chinese Pharmacopoeia(2020 edition) can be synthesized in rhizomes of Paris polyphylla var. yunnanensis cultured in vitro, but their total content fails to meet the standard(0.60% in Chinese Pharmacopoeia). Therefore, in vitro culture of the Paris polyphylla var. yunnanensis is feasible, but the culture conditions need to be further improved.
Chromatography, High Pressure Liquid ; Liliaceae ; Melanthiaceae ; Rhizome ; Saponins

Objective To investigate the diagnostic value of CT signs of ipsilateral central lymph node metastasis (ICLNM) in single papillary thyroid carcinoma (PTC) by multivariate regression analysis.Methods The CT data of 302 single PTC with diameter ＞1.0 cm confirmed by operation and pathology were retrospectively analyzed.The optimal thresholds of lymph node metastasis diameter were obtained by receiver operating characteristic (ROC) curve analysis.And multivariate regression analysis was used to analyze the relation between lymph node size,degree of enhancement,calcification or cystic degeneration,central turbidity,positive lateral cervical lymph nodes and the ICLNM positivity.Results In 302 PTC,the proportion of ICLNM positive and negative was 63.6％ (192/302) and 36.4％ (110/302),respectively.According to the ROC curve,with the increase of lymph node diameter,the sensitivity of diagnosing lymph node metastasis decreased and the specificity increased.When the threshold was 0.4 cm,Youden index was the largest (0.358),and the sensitivity and specificity was 50.5％ and 80.3％,respectively.Multivariate analysis showed that the diameter≥0.4 cm,high enhancement,central turbidity and lateral cervical lymph nodes positivity were the independent risk factors of ICLNM,and the OR values were 4.189[95％ CI (2.037-8.617)],3.875 [(95％ CI (1.561-9.617)],4.054[(95％CI (2.230-7.371)] and 8.735 [(95％ CI (1.093-69.831)],respectively.Calcification or cystic degeneration was not statistically significant in ICLNM.Conclusions The diameter ≥0.4 cm,high enhancement,central turbidity and lateral cervical lymph nodes positivity are the independent risk factors of ICLNM.Although calcification or cystic degeneration is not the independent risk factor,it has high accuracy for ICLNM positivity.The accurate identification of these signs can help surgeons to take a more thorough surgical treatment and has great significance to reduce postoperative recurrence.

Recent studies heve demonstrated that Akkermansia muciniphila (A.muciniphila) plays an important role in human health and disease , including regulating the development of the immune system and the metabolic phenotype of the host.This article reviews the research progress on A.muciniphila in recent years, focusing on the basic characteristics , the influencing factors of colonization , and the underlying mechanism of maintaining intestinal homeostasis of A.muciniphila.Additionally, the article summarizes the potential association between A.muciniphila and the chronic metabolic diseases such as obesity , atherosclerosis,diabetes mellitus and infectious diseases.The perspect of A.muciniphila as a new generation of probiotics in clinical medicine and the challenge for its industrialization are also discussed in the article .