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.

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Objective To analyze the cellular and histopathological characteristics of underdiagnosed thyroid nodules of Chinese thyroid imaging reporting and data system(C-TIRADS) categories 3 and 4a,thus improving the understanding of these lesions. Methods The data of ultrasound and fine needle aspiration cytology were collected from 683 nodules diagnosed based on pathological evidence in 549 patients undergoing thyroid surgery.The cellular and histopathological characteristics of C-TIRADS 3 and 4a nodules were analyzed. Results Two hundred and sixty-eight nodules were classified as C-TIRADS category 3,including 236 benign nodules,12 low-risk ones,and 20 (7.46%) malignant ones.Two hundred and twenty-one nodules were classified as C-TIRADS category 4a,including 133 benign nodules,7 low-risk ones,and 81 (36.65%) malignant ones.The malignancy rates differed between C-TIRADS 3 and 4a nodules (χ²=58.93,P<0.001),and both were higher than the recommended malignancy rate in the guidelines for malignancy risk stratification of thyroid nodules (C-TIRADS) (both P<0.001).According to the pathological evidence,the underdiagnosed C-TIRADS 3/4a nodules were mainly papillary thyroid carcinoma,especially in patients with Hashimoto thyroiditis.There was not a consistent one-to-one match between each ultrasound result and each cytological classification of low-risk thyroid nodules.Conclusions When the malignant features in preoprative ultrasound imaging are atypical or absent,papillary thyroid carcinoma (especially with Hashimoto thyroiditis),follicular carcinoma,and medullary carcinoma are likely to be underdiagnosed as C-TIRADS 3 or 4a nodules.Therefore,efforts should be made to fully understand the cellular and pathological characteristics of these lesions.
Humans ; Thyroid Nodule/diagnostic imaging* ; Female ; Male ; Middle Aged ; Adult ; Ultrasonography ; Biopsy, Fine-Needle ; Aged ; Young Adult ; Thyroid Neoplasms/diagnostic imaging* ; Adolescent

Objective To observe the clinical efficacy of Xingnao Kaiqiao Acupuncture(with the functions of awakening the brain and opening the orifices)combined with acupuncture at pericardium meridian points in the treatment of post-stroke sleep reversal(PSSR).Methods Sixty patients with PSSR were randomly divided into observation group and control group,30 patients in each group.Both groups were given conventional treatment,the control group was given oral use of Alprazolam,and the observation group was given the combination of acupuncture a at pericardial meridian points,and 10 days of treatment was one course of treatment.After 10 days of treatment,the clinical efficacy of the two groups was evaluated.The changes in the Pittsburgh Sleep Quality Index(PSQI)and Ascens Insomnia Scale(AIS)scores,as well as the Hamilton Depression Scale(HAMD)scores were observed before and after treatment in the two groups.The changes in cortisol levels at 0,8,and 16 o'clock were compared before and after treatment between the two groups.Results(1)After treatment,the PSQI scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the AIS and HAMD scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the AIS and HAMD scores,and the difference was statistically significant(P＜0.05).(3)After treatment,the cortisol level of patients in the two groups at 0,8,and 16 o'clock was significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the cortisol level at 0,8,and 16 o'clock was significantly superior to the control group,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 86.67%(26/30)in the observation group and 80.00%(24/30)in the control group.The efficacy of the observation group was slightly superior to that of the control group,but the difference was not statistically significant(P＞0.05).Conclusion Xingnao Kaiqiao Acupuncture combined with acupuncture at pericardium meridian points for the treatment of PSSR can significantly improve the clinical symptoms of the patients,so as to improve the quality of life of the patients,and the therapeutic efficacy is remarkable.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective:To explore the early predictive value of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram（aEEG）in small for gestational age（SGA）preterm infants with brain injury.Methods:One hundred and six cases of SGA preterm infants were enrolled in this study in Neonatology Department of Inner Mongolia People's Hospital from January 2019 to December 2021. Umbilical cord blood serum S100β protein and lactate at birth of All SGA preterm infants were tested，and aEEG was monitored at 6h and 72 h after birth，corrected gestational age of 32 weeks and 37 weeks. According to the diagnostic criteria of brain injury in preterm infants，SGA preterm infants were divided into brain injury group（45 cases）and non-brain injury group（61 cases），and compared the differences of S100β protein，lactate and the designated time aEEG between the two groups.SGA preterm infants with brain injury were further divided into symmetrical group（28 cases）and non-symmetrical group（15 cases）. The differences of umbilical cord blood S100β protein and lactate level between the two groups were compared，and the diagnostic value in different types of SGA preterm infants with brain injury was also compared.Results:SGA preterm infants in the brain injury group had significantly higher levels of umbilical cord blood S100β protein［（0.826±0.218）μg/L vs（0.397±0.196）μg/L， t=8.316， P<0.05］and lactate［（8.5±1.3）mmol/L vs（3.8±0.9）mmol/L， t=3.281， P<0.05］than those in non-brain injury group.Symmetric SGA group had higher level of S100β protein than the asymmetric SGA group［（0.924±0.205）μg/L vs（0.438±0.196）μg/L， t=5.734， P<0.05］.But there was no statistically significant difference in lactate levels［（5.6±1.4）mmol/L vs（3.9±1.2）mmol/L， t=0.932， P>0.05］between symmetric SGA group and asymmetric SGA group. The abnormal rates of aEEG in brain injury group and non-brain injury group were respectively 100%（45/45）vs 22.95%（14/61）at 6 h after birth，95.56%（43/45）vs 16.39%（10/61）at 72 h after birth，62.22%（28/45）vs 6.56%（4/61）at 32 weeks of corrected gestational age，22.22%（10/45）vs 3.28%（2/61）at 37 weeks of corrected gestational age. The abnormal rate of brain injury group was higher than the non-brain injury group in the same nodal time，and the differences were statistically significant（ χ 2 value respectively 62.292，64.913，38.074，9.257，all P<0.05）. Conclusion:There were significant value in umbilical cord blood S100β protein，lactate level and aEEG monitoring in the early diagnosis in preterm infants SGA with brain injury. The combination of the three might be more helpful for the early diagnosis and timely treatment of brain injury in SGA preterm infants.

Non-alcoholic fatty liver disease is a common chronic liver disease in clinical practice. In recent years, with increasing social attention to the health of women and the elderly, the prevention and treatment of non-alcoholic fatty liver disease after menopause has increasingly become a research hotspot in metabolic diseases. This study explores the pathogenesis and treatment method of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation" and combined with the physiological and pathological characteristics of postmenopausal women and the Western medicine understanding of non-alcoholic fatty liver disease. We believe that the pathogenesis of non-alcoholic fatty liver disease in postmenopausal women is rooted in the "deficient qi" caused by depletion of liver and kidney essence and blood. The imbalance between the physical and functional aspects of the liver due to this "deficient qi" is the primary factor, while the "stagnation" of phlegm and blood stasis is the manifestation. Furthermore, the "deficient qi" and "stagnation" reinforce each other, with the deficiency leading to stagnation and stagnation exacerbating the deficiency, thus accelerating the progression of the disease. The treatment approach should be one that combines nourishing deficiency and resolving stagnation, addressing both root cause and maifestations. Given the female characteristic of "the liver as the innate organ" and the post-menopausal physiological state of "gradual decline of kidney essence", it is important to focus on nourishing the liver and kidneys, nurturing the liver′s physical body while maintaining its function, and also promoting the circulation of qi, resolving phlegm, and invigorating blood circulation to remove blood stasis. This approach aims to reduce the accumulation of lipids in the liver, offering a new perspective and approach for the treatment of non-alcoholic fatty liver disease in post-menopausal women with traditional Chinese medicine.

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.