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.

Traditional Chinese medicine(TCM) resources are the essential material foundation for the development of TCM. The national survey of TCM resources serves as a periodic summary of these resources, ensuring the continuity, prosperity, and development of TCM in China. Since 1949, four national surveys of TCM resources have been conducted. The fourth survey incorporated an investigation into traditional knowledge related to TCM resources, including the traditional medicinal knowledge of Chinese ethnic minorities, with the goal of systematically exploring, preserving, and inheriting this knowledge. This manuscript provides an overview of the basic findings from the first three national surveys of TCM resources, while also clarifying the concepts, categories, forms, carriers, and acquisition pathways of traditional knowledge related to TCM resources. A preliminary summary of the findings from traditional knowledge investigations reported in current literature is also presented. Based on the fourth survey, this manuscript emphasizes the urgency of developing public medical knowledge through empirically-based investigations, the excavation, and compilation of traditional knowledge. It also outlines the potential for conducting "precise" investigations based on first-hand data obtained from the survey, as well as facilitating the discovery and evaluation of new medicines using traditional knowledge related to ethnic minority medicinal practices. This manuscript is expected to provide valuable insights for promoting the health and industrial development of ethnic minority populations in the post-"survey" phase.
Humans ; Medicine, Chinese Traditional ; China/ethnology* ; Minority Groups ; Ethnicity ; Drugs, Chinese Herbal/therapeutic use* ; Health Knowledge, Attitudes, Practice/ethnology* ; Surveys and Questionnaires

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.

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.

The key factors for producing the best quality Chinese herbal medicines are high-quality germplasm, suitable cultivation area and the proper processing methods for herbal raw materials. Gentiana crassicaulis in Gentiana (Sect. Cruciata), Gentianaceae is one of the original plants of the Chinese herb Qinjiao (Gentianae Macrophyllae Radix), and its type specimen was collected in Lijiang, Yunnan. There is a long planting history of the herb in this area. In this study a sampling plot was designated in these traditional planting areas. G. crassicaulis was planted and herbal raw materials were harvested from the plot. The raw materials were prepared locally and at a pharmaceutical factory in Shanghai using processing methods such as "sweating" or "no sweating", "slicing" or "no slicing" (whole root), and "stoving" or "no stoving" (air drying). The quality of all processed samples was evaluated. In addition, molecular markers were determined for identifying cultivated and wild samples from Lijiang, Yunnan. The results are as follows: ① Samples from the sampling plot and the field are taxonomically identified as Gentiana crassicaulis. ② A total of 270 sequences of trnC-GCA-petN, atpB-rbcL, psbN, ndhB-rps7 and ycf1 were obtained, and three genotypes were determined from the cultivated samples; the type III was shared by both cultivated and wild plants. Based on the molecular markers, a DNA barcoding method to identify cultivated and wild samples of G. crassicaulis from Lijiang, Yunnan was established. ③ Total content of loganic acid and gentiopicroside in all samples was ≥ 2.5%, and above the Chinese Pharmacopoeia (2020) limit. ④ In HPLC fingerprinting, 9 common peaks were assigned and similarity between all samples was > 0.999; and ⑤ In a PCA score plot all slice samples were clustered, while whole root samples were scattered. Therefore, our studies could provide basic data for optimizing the processing method, producing best quality Gentianae Macrophyllae Radix, and evaluating the quality of different ecotype varieties and the multiple origin of herbal medicines.

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*

OBJECTIVE: To investigate the role of long-chain non-coding RNA MALAT1 in modulating paclitaxel resistance in breast cancer cells. METHODS: Breast cancer SK-BR-3 cells were treated with gradient concentrations of paclitaxel to induce paclitaxel resistance of the cells. The resistant cells were transfected with si-NC, si-MALAT1, pcDNA, pcDNA-MALAT1, miRNC, miR-485-3p mimics, si-MALAT1+anti-miR-NC, or si-MALAT1+anti-miR-485-3p liposomes. Following the transfections, the cells were examined for changes in IC of paclitaxel using MTT assay; the protein expression of P-gp, Bcl-2 and Bax were detected with Western blotting, and a dual luciferase reporter assay was used to detect the binding of MALAT1 to miR-485-3p. RESULTS: Compared with paclitaxel-sensitive SK-BR-3 cells, paclitaxel-resistant SK-BR-3 cells showed significantly increased the IC of paclitaxel with up-regulated MALAT1 expression and down-regulated miR-485-3p expression ( < 0.05). Silencing MALAT1 or overexpressing miR-485-3p obviously lowered the IC of paclitaxel and the expression of P-gp and Bcl-2 and increased the expression of Bax in SK-BR-3/PR cells ( < 0.05). miR-485-3p was identified as the target of MALAT1, and inhibiting miR-485-3p significantly reverse the effect of MALAT1 silencing on IC of paclitaxel and the expressions of P-gp, Bcl-2 and Bax in SK-BR-3/PR cells ( < 0.05). CONCLUSIONS MALAT1 can modulate paclitaxel resistance in breast cancer cells possibly by targeting miR-485-3p to down-regulate P-gp and Bcl-2 and up-regulate Bax.
Cell Line, Tumor ; Humans ; MicroRNAs ; Paclitaxel ; RNA, Long Noncoding ; genetics

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.

Objective To study the prevalence trends and etiology of hand,foot,and mouth disease (HFMD) in hospitalized children.Methods The clinical data of 11 510 cases of children hospitalized with HFMD from 2008 to 2017 in Department of Infection Diseases of Kunming Children's Hospital were collected,and to retrospectively analyze the characteristics,time distribution and pathogen distribution of the cases.Results Of the 11 510 children with HFMD,6 100 were male and 5 410 were female.There were 9 814 cases under 3 years old,1 696 over 3 years old.HFMD occurred throughout the year.The peak months of the disease were April to July,with the time distribution of single peak.There were 4 690 severe cases and 3 452 critical cases,accounting for 70.34％.The main pathogens detected were enteroviruses A71 (EV-A71),coxsackievirus A16 (CV-A16) and other enteroviruses (EV),with 3 803 cases (36.02％),1 122 cases (10.63％) and 3 401 cases (32.21％) respectively.EV-A71 and CV-A16 infections dominated from 2008 to 2013,while EV-A71 and other EV infection dominated from 2014 to 2017.Conclusions EV-A71,CV-A16 and other EV are the main pathogens of HFMD in Kunming.Critical HFMD cases are mainly caused by EV-A71 infection.

Objective To investigate the correlation between ultrasound findings and clinical pathological types of adrenal cortical tumors(ACT).Methods The clinical data and ultrasonographic finding of 138 ACT patients undergoing surgical treatment in Affiliated Hospital of Qingdao University from January 2006 to December 2015 were retrospectively reviewed.The correlation between ultrasonic signs and pathological types of ACT was analyzed with Spearman method.Results There were 65 males and 73 females aged 18-71 years old.Among 138 cases,90 patients were characterized by hypertension,Cushing signs,Coon signs and abnormal sexual character, with the clinical diagnosis of adrenal cortical hyperplasia or adenoma;while 48 asymptomatic patients were first detected by ultrasonography.The coincidence rate of ultrasound and clinical pathological diagnosis was 92.0%(127/138),and 11 cases were misdiagnosed.The coincidence rate of ultrasound and surgical diagnosis was 94.2%(130/138), and 8 cases were misdiagnosed.The coincidence rate for no functional adenoma was 95.8%(46/48), for cortisol cortical adenoma was 94.1%(32/34),for aldosterone cortical adenoma was 93.6%(29/31),for cortical cysts was 9/10,for no functional adenocarcinoma was 5/6,for sexual abnormal cortical adenocarcinoma was 3/4,for cortisol cortical adenocarcinoma was 2/3,for mucous cortical adenoma was 1/2.The diameter of ACT was 0.6-11.5 cm.The low echo nodules of the adrenal region with a diameter <2.0 cm were associated with aldosterone cortical adenomas(r=0.485, P=0.01); the low echo or isoechoic nodules with a diameter 2.0-5.0 cm were associated with cortical adenomas or non-functional adenomas(r=0.567,0.452,P=0.01),and the circular non-echo nodules were associated with cortical cysts(r=0.483, P=0.01); the irregular nodules with a diameter >5.0 cm were associated with cortical adenocarcinoma(r=0.595, P=0.01).Conclusion The ultrasound image of ACT is related to different clinical pathological types,which can provide important information for clinical diagnosis and selection of surgical modalities.