1.Targeting PPARα for The Treatment of Cardiovascular Diseases
Tong-Tong ZHANG ; Hao-Zhuo ZHANG ; Li HE ; Jia-Wei LIU ; Jia-Zhen WU ; Wen-Hua SU ; Ju-Hua DAN
Progress in Biochemistry and Biophysics 2025;52(9):2295-2313
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.
2.Common characteristics and regulatory mechanisms of airway mucus hypersecretion in lung disease.
Ze-Qiang LIN ; Shi-Man PANG ; Si-Yuan ZHU ; Li-Xia HE ; Wei-Guo KONG ; Wen-Ju LU ; Zi-Li ZHANG
Acta Physiologica Sinica 2025;77(5):989-1000
In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans
;
Mucus/metabolism*
;
Mucins/physiology*
;
Lung Diseases/metabolism*
;
Respiratory Mucosa/metabolism*
;
Pulmonary Disease, Chronic Obstructive/physiopathology*
;
Asthma/physiopathology*
;
Cystic Fibrosis/physiopathology*
;
Mucociliary Clearance/physiology*
3.A quality improvement study on improving the follow-up rate of preterm infants after discharge.
He-Sheng CHANG ; Xue YANG ; Jun JU ; Wen-Ya XU ; Di WU ; Xiao-Man WAN ; Zheng-Hong LI
Chinese Journal of Contemporary Pediatrics 2025;27(2):148-154
OBJECTIVES:
To explore the measures to improve the follow-up rate of preterm infants after discharge, and to evaluate the effectiveness of these measures using quality improvement methodology.
METHODS:
The follow-up status of preterm infants discharged from March to May 2017 was used as the baseline before quality improvement, and a specific quality improvement goal for the follow-up rate was proposed. The Pareto chart was used to analyze the causes of follow-up failure, and a key driver diagram was constructed based on the links involved in improving follow-up rate. The causes of failure were analyzed to determine the key links and intervention measures for quality improvement, and the follow-up rate was monitored weekly using a control chart until the quality improvement goal was achieved.
RESULTS:
The follow-up rate of preterm infants after discharge was 57.92% (117/202) at baseline before quality improvement, and the quality improvement goal was set to increase the follow-up rate of preterm infants from baseline to more than 80% within 12 months. The Pareto chart analysis showed that the main causes of follow-up failure were deficiencies in follow-up file management and irregular follow-up times (33.70%, 31/92), insufficient follow-up education and poor communication (25.00%, 23/92), and the inability to meet the diverse needs of parents (18.48%, 17/92). Based on the key links for quality improvement and the main causes of follow-up failure, the following intervention measures were adopted: (1) strengthen follow-up publicity and education; (2) build a follow-up team; and (3) establish a follow-up platform and system. The control chart indicated that with the implementation of the above intervention measures, the weekly follow-up rate increased to 74.09% (306/413) in July 2017 and 83.09% (511/615) in December 2017, finally achieving the quality improvement goal. During the COVID-19 pandemic, the follow-up rate of preterm infants fluctuated between 23.54% (460/1 954) and 70.97% (1 931/2 721), and subsequently, it returned to pre-pandemic levels starting in February 2023.
CONCLUSIONS
The application of quality improvement methodology can help to formulate intervention measures based on the main causes of follow-up failure, thereby improving the follow-up rate of preterm infants after discharge. This quality improvement method is feasible and practical and thus holds promise for clinical application.
Humans
;
Quality Improvement
;
Infant, Premature
;
Infant, Newborn
;
Patient Discharge
;
Follow-Up Studies
;
Female
;
Male
4.Clinical efficacy of Wenshen Chushi Decoction combined with LIPUS on erectile dysfunction with renal deficiency and phlegm-dampness syndrome.
Wen-Xiong ZHU ; Yi-Feng YUAN ; Tao LIU ; Bo LI ; Liu-Ya LONG ; Qi-Hua CHEN ; Ju-Qiao HE
National Journal of Andrology 2025;31(6):519-525
OBJECTIVE:
To explore the clinical efficacy of Wenshen Chushi Decoction combined with low intensity pulsed ultrasound (LIPUS) on erectile dysfunction (ED) caused by renal deficiency and phlegm-dampness syndrome.
METHODS:
One hundred and twenty ED patients were included from the Department of Andrology in the First Hospital of Hunan University of Traditional Chinese Medicine. The patients in control group were treated with Wenshen Chushi Decoction. While the patients in observation group were treated with Wenshen Chushi Decoction combined with LIPUS for 8 consecutive weeks. After the treatment, the efficacy was evaluated using the International Index of Erectile Function-5 (IIEF-5) score, Penile Flow Index (PFI), Traditional Chinese Medicine Syndrome Score, Self-Rating Depression Scale (SDS) score, and Self-Rating Anxiety Scale (SAS) score. Safety was also observed. And the efficacy was followed up 4 weeks after the end of treatment.
RESULTS:
Fifty-seven cases were enrolled into control group finally with 55 cases in the treatment group. After the treatment, all the patients in both of groups showed an improvement in IIEF-5 scores (P<0.01). Compared with the control group (19.09 ± 2.22), the IIEF-5 score in observation group (20.42 ± 2.39) increased significantly (P<0.01). After the treatment, the scores of PFI, TCM syndrome and SDS in both groups decreased (P<0.01, P<0.05, P<0.01). Compared with the control group ([3.77 ± 1.21], [9.91 ± 1.71] and [39.88 ± 2.63] points), the observation group ([2.92 ± 1.08], [4.78 ± 1.45], and [34.51 ± 2.09] points) showed a more significant decrease (P<0.01). There was no significant difference in total effective rate between the two groups (P>0.05). During follow-up, the IIEF-5 scores of both groups of patients were higher than those before (P<0.05, P<0.01), and the observation group score was higher than that in the control group ([17.15 ± 3.37] vs [13.63 ± 1.96], P<0.01). No adverse reaction and abnormality of indicators occurred in both of two groups.
CONCLUSION
Wenshen Chushi Decoction has a significant therapeutic effect on ED caused by renal deficiency and phlegm-dampness syndrome. It can not only improve the quality of erection, but also improve the physical and mental symptoms associated with ED, which makes therapeutic effect lasting longer.
Humans
;
Male
;
Drugs, Chinese Herbal/therapeutic use*
;
Erectile Dysfunction/etiology*
;
Middle Aged
;
Adult
;
Treatment Outcome
;
Medicine, Chinese Traditional
;
Ultrasonic Therapy
;
Phytotherapy
5.Analysis of HA and NA gene variation characteristics of A(H1N1)pdm09 influenza virus in Shandong Province from 2022 to 2023
Ju-Long WU ; Shu ZHANG ; Yu-Jie HE ; Lin SUN ; Shao-Xia SONG ; Wen-Kui SUN ; Ti LIU
Chinese Journal of Zoonoses 2024;40(5):471-477
This study was aimed at characterizing the variations in hemagglutinin(HA)and neuraminidase(NA)genes of influenza virus subtype A(H1N1)pdm09 isolated during the 2022-2023 influenza monitoring year in Shandong Province,to provide a scientific basis for influenza prevention and control.A total of 14 A(H1N1)pdm09 subtype influenza strains were se-lected randomly by city by the influenza monitoring network laboratory.The vaccine strains recommended by the WHO served as references for whole gene sequencing analysis.A fluorescence method was used to conduct neuraminidase inhibition experi-ments to evaluate drug sensitivity.The A(H1N1)pdm09 influenza virus in Shandong Province,2022-2023 belonged to the 5a.2a evolutionary cluster in the 6B.1A branch.Nucleotide sequence analysis indicated that the HA and NA genes were closely re-lated to the Northern Hemisphere vaccine strain A/Victoria/2570/2019 in the years 2021-2023,and showed homology of 98.5%to 98.7%and 98.8%to 99.1%,respectively.Amino acid sequence analysis revealed 20 amino acid sequence mutations in the HA protein,but only one virus strain was found to have antigen drift,and three virus strains showed loss of HA protein glycosylation sites.No mutations were found at important sites affecting NA enzymes.The neuraminidase inhibition experiment indicated viral sensitivity to anti-influenza drugs.In conclusion,the monitored virus strains had high overall homology with vac-cine strains but showed some amino acid variation.In the future,continued monitoring of the genetic variation characteristics of influenza viruses will be necessary to understand the risk of influenza epidemics,and the effectiveness of influenza vaccines and therapeutic drugs.
6.Monitoring and analysis of avian influenza virus in poultry related environments in Shandong Province from 2020 to 2023
Ju-Long WU ; Shao-Xia SONG ; Yu-Jie HE ; Shu ZHANG ; Lin SUN ; Wen-Kui SUN ; Ti LIU ; Zeng-Qiang KOU
Chinese Journal of Zoonoses 2024;40(8):768-773
This study was aimed at understanding the pollution distribution pattern of avian influenza virus in the environ-ment in poultry related places in Shandong Province,to provide a scientific basis for the prevention,control,prediction,and early warning regarding human infection with avian influenza.From 2020 to 2023,6 523 environmental samples were collected in 16 cities in Shandong Province from four types of poultry-related places.Fluorescence quantitative PCR was used for nucleic acid testing of influenza A virus.Positive samples were further identified for the H5,H7,and H9 subtypes of avian influenza virus.The epidemiological characteristics of avian influenza viruses in the poultry related environment of Shandong Province were described,and inter-rate comparisons were performed with the x2 test.During 2020-2023,6 523 environmental samples were collected,and 1 007 cases positive for avian influenza virus were detected,with a positivity rate of 15.44%.H5,H7,and H9 subtypesand mixed infections were detected.H9 was the main subtype(88.48%)in positive specimens.A significant difference in positivity rates was observed among regions(x2=431.956,P<0.001),and the highest positivity rate was 28.93%.Significant differences in positivity rates were observed among monitoring sites(x2=304.604,P<0.001),sample types(x2=109.678,P<0.001),and quarters(x2=64.963,P<0.001).The positive detection rate was highest at monitoring sites in urban and rural live poultry markets(20.12%),and the positive detection rate of samples collected by wiping meat cut-ting board surfaces was higher than that of other samples(22.56%).The peak positive detection rate occurred in spring(20.31%).Widespread contamination with avian influenza virus was observed in poultry environments in Shandong Prov-ince.The H9 subtype,the main pathogen,coexisted with H5 and H7 subtypes,thus posing a risk of human infection with avian influenza.Therefore,prevention and control of avian influenza must be strengthened in key seasons,areas,places,and links.
7. Neurovascular coupling and central nervous system diseases
Ju-Xiang YANG ; Gang LI ; Nai-Hong CHEN ; Zhao ZHANG ; Shi-Feng CHU ; Nai-Hong CHEN ; Zhao ZHANG ; Wen-Bin HE ; Nai-Hong CHEN
Chinese Pharmacological Bulletin 2023;39(12):2225-2230
Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.
8.Exploring the treatment of sepsis-associated acute lung injury with Liangge Powder via ERK1/2 and PI3K/AKT pathways: based on network pharmacology and whole animal experimentation.
Rui HUANG ; Wen Ju HE ; Ping Ping ZHANG ; Dong Qiang WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(2):94-103
Objective: To investigate the therapeutic effect and mechanism of Liangge Powder against sepsis-induced acute lung injury (ALI) . Methods: From April to December 2021, the key components of Liangge Powder and its targets against sepsis-induced ALI were analyzed by network pharmacology, and to enrich for relevant signaling pathways. A total of 90 male Sprague-Dawley rats were randomly assigned to sham-operated group, sepsis-induced ALI model group (model group), Liangge Powder low, medium and high dose group, ten rats in the sham-operated group and 20 rats in each of the remaining four groups. Sepsis-induced ALI model was established by cecal ligation and puncture. Sham-operated group: gavage with 2 ml saline and no surgical treatment. Model group: surgery was performed and 2 ml saline was gavaged. Liangge Powder low, medium and high dose groups: surgery and gavage of Liangge Powder 3.9, 7.8 and 15.6 g/kg, respectively. To measure the wet/dry mass ratio of rats lung tissue and evaluate the permeability of alveolar capillary barrier. Lung tissue were stained with hematoxylin and eosin for histomorphological analysis. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6 and IL-1β in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The relative protein expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-protein kinase B (AKT), and p-ertracellular regulated protein kinases (ERK) were detected via Western blot analysis. Results: Network pharmacology analysis indicated that 177 active compounds of Liangge Powder were selected. A total of 88 potential targets of Liangge Powder on sepsis-induced ALI were identified. 354 GO terms of Liangge Powder on sepsis-induced ALI and 108 pathways were identified using GO and KEGG analysis. PI3K/AKT signaling pathway was recognized to play an important role for Liangge Powder against sepsis-induced ALI. Compared with the sham-operated group, the lung tissue wet/dry weight ratio of rats in the model group (6.35±0.95) was increased (P<0.001). HE staining showed the destruction of normal structure of lung tissue. The levels of IL-6 [ (392.36±66.83) pg/ml], IL-1β [ (137.11±26.83) pg/ml] and TNF-α [ (238.34±59.36) pg/ml] were increased in the BALF (P<0.001, =0.001, <0.001), and the expression levels of p-PI3K, p-AKT and p-ERK1/2 proteins (1.04±0.15, 0.51±0.04, 2.31±0.41) were increased in lung tissue (P=0.002, 0.003, 0.005). The lung histopathological changes were reduced in each dose group of Liangge Powder compared with the model group. Compared with the model group, the wet/dry weight ratio of lung tissue (4.29±1.26) was reduced in the Liangge Powder medium dose group (P=0.019). TNF-α level [ (147.85±39.05) pg/ml] was reduced (P=0.022), and the relative protein expression levels of p-PI3K (0.37±0.18) and p-ERK1/2 (1.36±0.07) were reduced (P=0.008, 0.017). The wet/dry weight ratio of lung tissue (4.16±0.66) was reduced in the high-dose group (P=0.003). Levels of IL-6, IL-1β and TNF-α[ (187.98±53.28) pg/ml, (92.45±25.39) pg/ml, (129.77±55.94) pg/ml] were reduced (P=0.001, 0.027, 0.018), and relative protein expression levels of p-PI3K, p-AKT and p-ERK1/2 (0.65±0.05, 0.31±0.08, 1.30±0.12) were reduced (P=0.013, 0.018, 0.015) . Conclusion: Liangge Powder has therapeutic effects in rats with sepsis-induced ALI, and the mechanism may be related to the inhibition of ERK1/2 and PI3K/AKT pathway activation in lung tissue.
Male
;
Animals
;
Rats
;
Rats, Sprague-Dawley
;
Proto-Oncogene Proteins c-akt
;
Phosphatidylinositol 3-Kinase
;
Phosphatidylinositol 3-Kinases
;
Powders
;
Animal Experimentation
;
Interleukin-6
;
MAP Kinase Signaling System
;
Network Pharmacology
;
Tumor Necrosis Factor-alpha
;
Acute Lung Injury/drug therapy*
;
Sepsis/drug therapy*
9.MiR-663a Inhibits Radiation-Induced Epithelium-to-Mesenchymal Transition by Targeting TGF-β1.
Pei QU ; Zhi Ang SHAO ; Bing WANG ; Jin Peng HE ; Ya Nan ZHANG ; Wen Jun WEI ; Jun Rui HUA ; Heng ZHOU ; Dong LU ; Nan DING ; Ju Fang WANG
Biomedical and Environmental Sciences 2022;35(5):437-447
Objective:
miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT).
Methods:
TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified.
Results:
Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation.
Conclusion
Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.
Down-Regulation
;
Epithelial-Mesenchymal Transition
;
Epithelium/metabolism*
;
MicroRNAs/metabolism*
;
Transforming Growth Factor beta1/pharmacology*
10.A comparison of R-CHOP and R-DA-EPOCH as a first-line regimen treatment of diffuse large B cell lymphoma with non-GCB subtypes: a retrospective study.
Zi Yan HE ; Wen Juan YU ; Shan Shan SUO ; Jing Han WANG ; Hai Tao MENG ; Wen Yuan MAI ; Ju Ying WEI ; Min YANG ; Li Ping MAO ; Jie JIN
Chinese Journal of Hematology 2022;43(4):346-348
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Cyclophosphamide/therapeutic use*
;
Doxorubicin/therapeutic use*
;
Etoposide
;
Humans
;
Lymphoma, Large B-Cell, Diffuse/pathology*
;
Prednisone/therapeutic use*
;
Prognosis
;
Retrospective Studies
;
Rituximab/therapeutic use*
;
Vincristine/therapeutic use*

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