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.Application of NRS 2002 and PG-SGA in Patients With Gastrointestinal Malignancies
Lijiang YOU ; Jie GE ; Ting LIU ; Tingyu ZHAO ; Kaiqiang XIE ; Heli LIU ; Mimi TANG
Chinese Journal of Gastroenterology 2023;28(12):738-742
Background:At present,domestic guidelines and consensus recommend the use of nutritional risk screening 2002(NRS 2002)and patient-generated subjective global assessment(PG-SGA)for nutritional risk screening and assessment of patients with gastrointestinal cancer during the perioperative period.However,PG-SGA has higher professional requirements,complex content and time-consuming.In the current busy situation of medical staff,NRS 2002 is more used for screening alone.Aims:To explore the consistency of NRS 2002 and PG-SGA in the assessment of nutritional status and clinical outcomes in patients with gastrointestinal malignancies,and to explore the accuracy of screening using NRS 2002 alone,so as to provide guidance for the establishment of clinical nutritional screening and assessment standards.Methods:A retrospective analysis was conducted on 157 patients with gastrointestinal malignancies who underwent radical operation in the Department of Gastrointestinal Surgery of Xiangya Hospital,Central South University from January 2020 to October 2022.Nutritional screening and evaluation were performed by NRS 2002 and PG-SGA scales and demographic data and nutrition-related laboratory indicators were collected to observe short-term postoperative clinical outcomes.Results:Patients with nutritional risk or malnutrition had lower body mass index(BMI),lymphocytes and prealbumin(P<0.05).The correlation and consistency of NRS 2002 and PG-SGA scales were good(r=0.728,κ=0.46)and the areas under the curve(AUC)for predicting postoperative complications were 0.691 and 0.702,respectively.In addition,nutritional risk and postoperative complications were significantly increased in patients with malnutrition(P<0.05).Conclusions:Therefore,gastrointestinal surgeons can only use NRS2002 to perform nutritional screening of patients and make corresponding nutritional treatment according to the screening results in the case of busy clinical work.
3.Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection.
Xin Hua WU ; Zhang Rong CHEN ; Ze Yuan HE ; Yu DONG ; Ying YANG ; Qiu Yan ZHAO ; Wei YANG ; Li Ying WANG ; Cai Jun FU ; Xiao Dan YANG ; Hong LIU
Chinese Journal of Cardiology 2022;50(6):577-584
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*
4.The role of histone demethylase KDM2A on airway inflammation and airway remodeling in a rat asthma model
Zhixia Wang ; Xiang Luo ; Lijiang Wang ; Yan Liu ; Chun Guo ; Yang Yang ; Zhiqiang Zhang
Acta Universitatis Medicinalis Anhui 2022;57(4):610-615
Objective:
To investigate the role of protein demethylase of lysine-specific demethylase 2 A(KDM2 A) in airway inflammation and remodeling in rats with bronchial asthma.
Methods:
Intraperitoneal injection of chicken ovalbumin(OVA) sensitized aerosol to stimulate the asthma rat model. Eighteen 6-8 weeks old SPF SD female rats were randomly divided into 3 groups, namely the control group, the asthma group for 4 weeks, and the asthma group for 8 weeks. After the success of the asthma model, the infiltration of inflammatory cells in the trachea and perivascular of the lung tissue was observed by HE staining; Goblet cell proliferation and mucus secretion were observed by PAS staining; Masson staining was used to observe the fibrosis of airway wall; The proliferation of airway smooth muscle was observed by fluorescence immunohistochemistry; The protein expression level of KDM2 A was detected by Western blot.
Results:
The inflammatory scores and inflammatory cell counts of rats in the asthma 4-week group and the asthma 8-week group were higher than those in the control group. There was a statistically significant difference in the above indicators between the asthma two groups(P<0.01). Compared with the control group, the proliferation of goblet cells and mucus secretion in the airway epithelium, the deposition of collagen fibers in the lung tissue and the proliferation of bronchial smooth muscle cells increased in the asthma groups(P<0.01). With the prolonged OVA sensitization time, airway inflammation and airway remodeling changes were more severe in the asthma 8-week group than those in the asthma 4-week group. The results of Western blot showed that the expression of KDM2 A in the lung tissues of the asthmatic 4-week group and the asthmatic 8-week group was higher than that of the control group, and the expression of KDM2 A in the asthma 8-week group was also higher than that of the asthma 4-week group. The differences were statistically significant(P<0.01). The expression of KDM2 A protein in lung tissue of rats in each group was positively correlated with airway inflammation score, total number of inflammatory cells, goblet cell mucus secretion score, lung tissue fibrosis ratio, and airway smooth muscle hyperplasia area(allP<0.01).
Conclusion
KDM2 A may play an important role in the pathogenesis of airway inflammation and airway remodeling in bronchial asthma.
5.Protective effects and mechanism of trehalose on ischemia-reperfusion injury in liver
Lijiang WANG ; Likun ZHUANG ; Tongwang YANG ; Jianyu LIU ; Shangheng SHI ; Yuntai SHEN ; Xiangwei HUA ; Peng LIU ; Peng ZHAO ; Yunjin ZANG
Chinese Journal of Organ Transplantation 2021;42(2):109-115
Objective ::To investigate the role of trehalose in hepatic ischemia-reperfusion injury and its underlying mechanisms.Methods:C57BL/6J mice were randomly divided into no-ischemia group, ischemia-reperfusion group, trehalose-treated group and normal saline control group. After ischemia for 90 minutes, reperfusion immediately or 6h, blood and liver tissues were collected, and serum was separated. The liver function parameters of ALT, AST, the inflammatory factors of TNF-α, IL-1β and IL-2, and the pathological changes of liver were detected to study the role of trehalose during hepatic ischemia-reperfusion injury. Hypoxia-reoxygenation cell model was established by AML12 mouse hepatocyte line, and divided into experimental group and control group. The experimental group was divided into low dose group and high dose group according to the concentration of trehalose administrated. And the control group had no use of trehalose. The level of apoptosis was measured to study the effect of trehalose on apoptosis induced by hepatic ischemia-reperfusion injury with flow cytometry. Western blot was utilized for detecting the levels of Caspase-3, Cleaved Caspase-3 and Bcl-2 protein to understand the molecular mechanisms of trehalose in apoptosis during hepatic ischemia-reperfusion injury.Results:In vivo animal experiments showed that liver function and such inflammatory factors as ALT, AST, TNF-α, IL-1β and IL-2 increased in ischemia-reperfusion group after hepatic ischemia-reperfusion ( P<0.05), and liver tissue became necrotic. After a treatment of trehalose, the levels of ALT, AST, TNF-α, IL-1β and IL-2 were lower than those of normalsaline control group and the area of liver tissue necrosis also decreased ( P<0.05). In vitro cell experiments showed that the apoptosis level of hepatocytes in the experimental group decreased compared with the control group.And the level of activated pro-apoptotic protein Cleaved Caspase-3 decreased, the level of anti-apoptotic protein Bcl-2 increased. Conclusions:Trehalose has protective effects on hepatic ischemia-reperfusion injury in vivo and in vitro. The mechanism may be involved in inhibiting inflammation induced by hepatic ischemia-reperfusion injury, suppressing the activation of Caspase-3 and promoting the expression of Bcl-2, thus played a protective role by extenuation of hepatocyteapoptosis.
6.Usage of ethnomedicine on COVID-19 in China.
Zhi-Yong LI ; Ya TU ; Hai-Tao LI ; Jiang HE ; QUESHENG ; Guang-Ping DONG ; Ming-Shuo ZHANG ; Jian-Qin LIU ; Xiu-Lan HUANG ; Xiao-Rong WANG ; Makabel BOLAT ; Xin FENG ; Fang-Bo ZHANG ; Feng JIANG
China Journal of Chinese Materia Medica 2020;45(10):2265-2274
In December 2019, an outbreak of viral pneumonia began in Wuhan, Hubei Province, which caused the spread of infectious pneumonia to a certain extent in China and neighboring countries and regions, and triggered the epidemic crisis. The coronavirus disease 2019(COVID-19) is an acute respiratory infectious disease listed as a B infectious disease, which is managed according to standards for A infectious disease. Traditional Chinese medicine and integrated traditional Chinese and Western medicine have played an active role in the prevention and control of this epidemic. China's ethnomedicine has recognized infectious diseases since ancient times, and formed a medical system including theory, therapies, formula and herbal medicines for such diseases. Since the outbreak of the COVID-19 epidemic, Tibet Autonomous Region, Qinghai Province, Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region and Chuxiong Autonomous Prefecture of Yunnan, Qiandongnan Autonomous Prefecture of Guizhou have issued the prevention and control programs for COVID-19 using Tibetan, Mongolian, Uygur, Yi and Miao medicines. These programs reflect the wisdom of ethnomedicine in preventing and treating diseases, which have successfully extracted prescriptions and preventive measures for the outbreak of the epidemic from their own medical theories and traditional experiences. In this paper, we summarized and explained the prescriptions and medicinal materials of ethnomedicine in these programs, and the origin of Tibetan medicine prescriptions and Mongolian medicine prescriptions in ancient books were studied. These become the common characteristics of medical prevention and treatment programs for ethnomedicine to formulate therapeutic programs under the guidance of traditional medicine theories, recommend prescriptions and prevention and treatment methods with characteristics of ethnomedicine, and focus on the conve-nience and standardization. However, strengthening the support of science and technology and the popularization to the public, and improving the participation of ethnomedicine in national public health services and the capacity-building to deal with sudden and critical diseases are key contents in the development of ethnomedicine in the future.
Betacoronavirus
;
China
;
Coronavirus Infections
;
drug therapy
;
Humans
;
Medicine, Traditional
;
Pandemics
;
Pneumonia, Viral
;
drug therapy
;
Tibet
7.Analysis of prognosis and pregnancy outcomes of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer
Yiqin WANG ; Rong ZHOU ; Lijiang XU ; Meng XIA ; Qun LU ; Guoli LIU ; Danhua SHEN ; Gang WANG ; Mian HE ; Jianliu WANG
Chinese Journal of Obstetrics and Gynecology 2020;55(5):327-332
Objective:To investigate the efficacy and pregnancy outcome of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer (EC).Methods:Clinical data was retrospectively collected for EC or atypical endometrial hyperplasia (AEH) patients treated in Peking University People's Hospital, Foshan First People's Hospital of Guangdong Province and First Affiliated Hospital of Sun Yat-sen University, from 2010 to 2019. Inclusion criteria for fertility-preserving treatment included: (1) Age ≤45 years. (2) EC with histological differentiation of G 1, G 2 or endometrial AEH. (3) EC disease should be stage Ⅰa, confined to the endometrium without myometrial invasion, lymph node or extrauterine metastasis. Treatment regimen: patients were given oral progestin therapy and endometrial pathology was evaluated every three months. Patients were divided into three groups as G 2 EC group, G 1 EC group and AEH group based on the histological differentiation. Oncological and pregnancy outcomes were compared among them. Results:(1) Totally 57 eligible patients were included in this study, including 11 cases with G 2 EC, 22 cases with G 1 EC, and 24 cases with AEH. (2) Oncological outcome: among the three groups of G 2 EC, G 1 EC and AH, the complete remission rates (9/11, 91% and 96%, respectively) and recurrence rates (3/9, 30% and 22%, respectively) were not significantly different (all P>0.05). Median remission time was significantly longer in the G 2 EC group than those in the other two groups (8, 6 and 4 months; P=0.046). Among 9 G 2 EC patients who recurred after complete remission, three patients relapsed at 7, 18 and 53 months, respectively. All 3 patients chose fertility-sparing treatment again, and all achieved complete remission after retreatment. (3) Pregnancy outcome: among the three groups, the assisted reproduction technology rates (4/8, 5/18 and 36%, respectively) and pregnancy rates (6/8, 5/18 and 36%, respectively) had no significant difference ( P>0.05). However, time interval to pregnancy was shorter in G 2 EC patientsthan the other two groups (4, 9 and 22 months, respectively; P=0.006). Conclusions:Fertility-preserving treatment for patients with stageⅠa, G 2 endometrial cancer, may obtain a relatively high remission rate and an acceptable pregnancy rate. However, further exploration is needed due to the limited number of cases.
8.Analysis of the relationship between long-term exposure to PM2.5 and sex hormone levels of female sanitation workers in Urumqi
Lijiang ZHANG ; Jun LIU ; Wenlan YU ; Yan REN ; Pu ZHANG ; Changyan YU ; Hua HE
Chinese Journal of Preventive Medicine 2020;54(8):888-891
From June 2017 to June 2018, female sanitation workers engaged in road cleaning in a district of Urumqi City, as well as government and logistics women participating in national health examination in the same community were recruited as particulate matter 2.5 (PM 2.5) exposure group and control group respectively. The contents of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the PM 2.5 exposed group were lower than those in the control group (all Pvalues < 0.05). Further analysis showed that the content of FSH in the exposure group at the age of 35-39, 40-44 and 45-49 years old was lower than that of the control group (all Pvalues < 0.05). The content of LH in the exposed group at the age of 35-39 and 45-49 years old was lower than that of the control group (all Pvalues < 0.05). The content of FSH in the exposed group with the length of service less than 5, about 5-9 and more than 10 years was lower than that of the control group (all Pvalues < 0.05). The content of LH in the exposed group with the length of service about 5-9 and more than 10 year was lower than that of the control group (all Pvalues < 0.05).
9.Analysis of the relationship between long-term exposure to PM2.5 and sex hormone levels of female sanitation workers in Urumqi
Lijiang ZHANG ; Jun LIU ; Wenlan YU ; Yan REN ; Pu ZHANG ; Changyan YU ; Hua HE
Chinese Journal of Preventive Medicine 2020;54(8):888-891
From June 2017 to June 2018, female sanitation workers engaged in road cleaning in a district of Urumqi City, as well as government and logistics women participating in national health examination in the same community were recruited as particulate matter 2.5 (PM 2.5) exposure group and control group respectively. The contents of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the PM 2.5 exposed group were lower than those in the control group (all Pvalues < 0.05). Further analysis showed that the content of FSH in the exposure group at the age of 35-39, 40-44 and 45-49 years old was lower than that of the control group (all Pvalues < 0.05). The content of LH in the exposed group at the age of 35-39 and 45-49 years old was lower than that of the control group (all Pvalues < 0.05). The content of FSH in the exposed group with the length of service less than 5, about 5-9 and more than 10 years was lower than that of the control group (all Pvalues < 0.05). The content of LH in the exposed group with the length of service about 5-9 and more than 10 year was lower than that of the control group (all Pvalues < 0.05).
10. A systematic review of the effects of auricular acupressure therapy on relieving acute and chronic nonmalignant pain and its operating methods
Miaomiao LIU ; Yingge TONG ; Ling CHAI ; Xiaoyan LI ; Jiajia CHEN
Chinese Journal of Practical Nursing 2019;35(26):2072-2081
Objective:
To evaluate the effect and implementation of auricular acupressure therapy (AAT) in the treatment of acute and chronic non-cancerous pain.
Methods:
Computer search China Knowledge Network, China Biomedical Literature Disc (CBM), Wanfang Database, Weip Chinese Science and Technology Journal Database, PubMed, Web of Science, EMbase, Ebsco, Cochrane databases, a randomized controlled trial of AAT in the treatment of acute and chronic non-cancerous pain was included. The main outcome of AAT treatment for pain was pain intensity and analgesic drug use.
Results:
Of the 29 studies included, 93.1% (27/29) indicated that AAT was effective in relieving pain and/or reducing the amount of analgesic drugs; 15 and 12 of them were for acute and chronic non


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