1.The mechanism of Laggerae Herba in improving chronic heart failure by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway
Jinling XIAO ; Kai HUANG ; Xiaoqi WEI ; Xinyi FAN ; Wangjing CHAI ; Jing HAN ; Kuo GAO ; Xue YU ; Fanghe LI ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):343-353
Objective:
To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice.
Methods:
Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue.
Results:
Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group.
Conclusion
Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.
2.Establishment and evaluation of an animal model of heart failure with preserved ejection fraction integrating disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis
Xiaoqi WEI ; Xinyi FAN ; Feng JIANG ; Wangjing CHAI ; Jinling XIAO ; Fanghe LI ; Kuo GAO ; Xue YU ; Wei WANG ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):501-515
Objective:
This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively.
Methods:
The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model.
Results:
Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group.
Conclusion
This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.
3.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine:Aural Vertigo
Yingdi GONG ; Zhanfeng YAN ; Wei FENG ; Daxin LIU ; Jiaxi WANG ; Jianhua LIU ; Yu ZHANG ; Shusheng GONG ; Guopeng WANG ; Chunying XU ; Xin MA ; Bo LI ; Shuzhen GUO ; Mingxia ZHANG ; Jinfeng LIU ; Jihua GUO ; Zhengkui CAO ; Xiaoxiao ZHANG ; Zhonghai XIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):215-222
Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine (TCM) mainly involves peripheral vestibular diseases of Western medicine, such as Meniere's disease, benign paroxysmal positional vertigo, vestibular neuritis, and vestibular migraine, being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo, aural vertigo affecting the quality of life, aural vertigo not relieved after surgery, aural vertigo with complex causes, and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM: Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo, the control and mitigation of the symptoms, and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.
4.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
5.The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial
Leilei DUAN ; Yubin ZHAO ; Yuliang ER ; Pengpeng YE ; Wei WANG ; Xin GAO ; Xiao DENG ; Ye JIN ; Yuan WANG ; Cuirong JI ; Xinyan MA ; Cong GAO ; Yuhong ZHAO ; Suqiu ZHU ; Shuzhen SU ; Xin'e GUO ; Juanjuan PENG ; Yan YU ; Chen YANG ; Yaya SU ; Ming ZHAO ; Lihua GUO ; Yiping WU ; Yangnu LUO ; Ruilin MENG ; Haofeng XU ; Huazhang LIU ; Huihong RUAN ; Bo XIE ; Huimin ZHANG ; Yuhua LIAO ; Yan CHEN ; Linhong WANG
Chinese Journal of Epidemiology 2024;45(2):250-256
Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.
6.TCM-HIN2Vec: A strategy for uncovering biological basis of heart qi deficiency pattern based on network embedding and transcriptomic experiment
Lihong Diao ; Xinyi Fan ; JIang Yu ; Kai Huang ; Edouard C Nice ; Chao Liu ; Dong Li ; Shuzhen Guo
Journal of Traditional Chinese Medical Sciences 2024;11(3):264-274
Objective:
To elucidate the biological basis of the heart qi deficiency (HQD) pattern, an in-depth understanding of which is essential for improving clinical herbal therapy.
Methods:
We predicted and characterized HQD pattern genes using the new strategy, TCM-HIN2Vec, which involves heterogeneous network embedding and transcriptomic experiments. First, a heterogeneous network of traditional Chinese medicine (TCM) patterns was constructed using public databases. Next, we predicted HQD pattern genes using a heterogeneous network-embedding algorithm. We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq. Finally, we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.
Results:
Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism, signal transduction pathways, and immune processes. Moreover, we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern. Furthermore, herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.
Conclusion
Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes, but also deciphering the basis of HQD pattern. Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns, leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.
7.Chlorogenic acid ameliorates heart failure by attenuating cardiomyocyte ferroptosis
Kai Huang ; Fanghe Li ; Jiayang Tang ; Haiyin Pu ; Vasily Sukhotukov ; Alexander N Orekhov ; Shuzhen Guo
Journal of Traditional Chinese Medical Sciences 2024;11(2):191-198
Objective:
To elucidate the effects of chlorogenic acid (CGA), a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods, including Lonicera japonica Thunb. (Jin Yin Hua), Eucommia ulmoides Oliv. (Du Zhong Ye), tea, and coffee, on cardiomyocyte ferroptosis and heart failure.
Methods:
We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction (TAC). These indicators included the left ventricular ejection fraction (LVEF), fractional shortening (LVFS), end-systolic volume (LVESV), end-diastolic volume (LVEDV), end-systolic diameter (LVESD), and end-diastolic diameter (LVEDD). An isoprenaline hydrochloride (ISO)-induced H9c2 cardiomyocyte cell model was also established, and the cells were treated with various concentrations of CGA. To assess the effect of CGA on ferroptosis in cardiomyocytes, we measured cell viability and evaluated the levels of intracellular reactive oxygen species (ROS), ferrous ions (Fe2+), and lipid peroxidation using fluorescent staining. To clarify the ferroptosis signaling pathway regulated by CGA, western blotting was used to examine the expression of ferroptosis biomarkers, specifically solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), in H9c2 cardiomyocytes and mouse myocardial tissues.
Results:
CGA significantly enhanced cardiac performance indices such as LVEF, LVFS, LVESV, LVEDV, LVESD, and LVEDD. H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels, Fe2+ content, and lipid peroxidation levels. However, CGA treatment significantly ameliorated these changes. Additionally, in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC, CGA increased the expression of ferroptosis-related proteins, including SLC7A11 and GPX4.
Conclusion
CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling pathway. This process alleviates ferroptosis in cardiomyocytes. These results provide new insights into the clinical use of CGA and the management of heart failure.
8.Visual analysis of nurses′psychological contract research based on CiteSpace
Suyun GUO ; Lanlai SHI ; Yihua YANG ; Shuzhen CHEN ; Danjuan LI
Chinese Journal of Practical Nursing 2024;40(32):2527-2536
Objective:To visualize and analyze the literature related to nurses′ psychological contract at home and abroad by CiteSpace software, discuss the development trend, and to provide reference for subsequent research.Methods:Literature related to nurses′ psychological contract collected by China National Knowledge Infrastructure and Web of Science from the establishment of the database to August 31, 2023 were retrieved. CiteSpace software was used to visually process the authors, institutions, keywords, publication trends and other types of nodes. Combined with the visualization map, the research status and hot trends of nurses′ psychological contract were analyzed.Results:A total of 175 articles in English and 126 articles in Chinese were included. The annual publication volume showed a zigzag upward trend. Chen Furong′s team published the most Chinese literature, while Rodwell J′s team published the most English literature. Shanxi Medical University and Monash University were the research institutions with the largest number of publications in Chinese and English respectively. Domestic research hotspots mainly focused on 5 directions: the status quo investigation, influence factors, intervention strategies, the impact on performance behavior, the content and structure of nurses′ psychological contract. Foreign research hotspots mainly focused on 3 directions: the influence factors, intervention strategies and the impact on performance behavior.Conclusions:The overall number of papers published in the field of nurses′psychological contract research at home and abroad is small, and the depth and breadth of the research are far from enough. The cooperation between authors and institutions should be strengthened, the research direction should be more diversified, and the mediation effect analysis and influence mechanism research of psychological contract should be paid attention to, so as to construct a multipath nurses′psychological contract system complied with national condition.
9.Establishment and Evaluation of Heart Failure Model with Qi Deficiency Syndrome
Jiang YU ; Jiayang TANG ; Shuai LI ; Xiang LI ; Haiyin PU ; Yu PENG ; Fanghe LI ; Shuzhen GUO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(15):60-67
ObjectiveTo establish and evaluate a mouse model of heart failure with Qi deficiency syndrome. MethodForty-four KM mice were randomly divided into sham operation group, model group, and modified Si Junzitang group (12.89 g·kg-1). The model group and the modified Si Junzitang group underwent thoracic aortic constriction (TAC), while the sham operation group only underwent suture without constriction. Echocardiography and pathological examination were used to assess the heart failure model and evaluate the pharmacological effects. Macroscopic characterization, microscopic biology, and formula identification were conducted to collect general signs, body weight, open-field behavior, grip strength, mitochondrial ultrastructure, and other macroscopic and microscopic characteristics of mice. Mitochondrial fission and fusion protein expression were measured to determine the syndrome type. ResultEight weeks after TAC, compared with the sham operation group, the model group showed a significant decrease in left ventricular ejection fraction (LVEF) (P<0.01), and modified Si Junzitang improved LVEF in mice (P<0.05). Hematoxylin-eosin (HE) staining of the heart showed inflammatory cell infiltration and thickening of blood vessel walls in the model group, which was significantly improved by modified Si Junzitang. After 6-8 weeks, compared with the sham operation group and the modified Si Junzitang group, the model group exhibited significant hair loss, hair yellowing, decreased activity, and depression. Moreover, compared with the sham operation group, the model group had a significantly lower increase in body weight (P<0.05), while the modified Si Junzitang group showed a significant increase in body weight (P<0.05) compared with the model group. After 6-8 weeks, compared with the sham operation group, the model group showed a significant decrease in open-field distance and speed (P<0.05), while the modified Si Junzitang group exhibited significantly improved open-field distance and speed in the 8th week (P<0.05). After 6-8 weeks, compared with the sham operation group, the model group exhibited a significant decrease in maximum grip strength (P<0.05), while the modified Si Junzitang group showed a significant increase in maximum grip strength 8 weeks after TAC (P<0.05). Transmission electron microscopy of the gastrocnemius muscle showed uneven muscle tissue matrix, mitochondrial swelling, increased volume, matrix dissolution, ridge loss, and vacuolization in the model group, while modified Si Junzitang improved mitochondrial swelling, ridge fracture, and matrix vacuolization. Western blot analysis showed that the expression of the kinetic associated protein 1 (DRP1) in the gastrocnemius muscle of the model group significantly increased (P<0.01), and the expression of mitochondrial fusion hormone 1 (MFN1) significantly decreased (P<0.05) as compared with those in the sham operation group. Furthermore, compared with the model group, the modified Si Junzitang group exhibited a significant decrease in the expression of DRP1 (P<0.05) and a significant increase in MFN1 expression (P<0.01). ConclusionMice exhibited significant manifestations of qi deficiency syndrome 6-8 weeks after TAC, accompanied by abnormal mitochondrial morphology and function in the gastrocnemius muscle, which were significantly improved by modified Si Junzitang.
10.Advantages of Traditional Chinese Medicine in Treating Dominant Disease: Allergic Rhinitis
Lili LIU ; Daxin LIU ; Jinfeng LIU ; Shuzhen GUO ; Zhonghai XIN ; Renzhong WANG ; Li TIAN ; Kuiji WANG ; Mingxia ZHANG ; Shirui YANG ; Shufan GUO ; Yonggang LIU ; Wei ZHANG ; Lingyan JIANG ; Hui CHEN ; Xing LIAO ; Geng LI ; Chenyu CHI ; Xiaoxiao ZHANG ; Zhanfeng YAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(2):203-211
In response to the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance, Innovation, and Development of traditional Chinese medicine(TCM) and the spirit of the National Conference on TCM, Chinese Association of Chinese Medicine organized experts in Otorhinolaryngology Head and Neck Surgery of traditional Chinese and western medicine to discuss the clinical advantages of TCM and integrated traditional Chinese and western medicine in the treatment of allergic rhinitis (AR) and they reached a basic consensus. In recent years, the prevalence of AR has been on the rise, threatening the quality of life of patients and giving rise to a heavy burden to both the patients and the society. AR is resulted from immune imbalance rather than reduced immunity or hyperimmunity, and the imbalance is similar to the Yin-yang disharmony in TCM. In the treatment of this disease, western medicine features rapid onset. However, it is cost-intensive and causes severe surgical trauma, and the recurrence is common. TCM boasts diverse methods for AR, which can be used in all stages of this disease. It has advantages in controlling symptoms such as nasal congestion, runny nose, or dysosmia in the attack stage, preventing recurrence in the remission stage, and treating refractory AR or steroid-resistant AR. In particular, acupuncture enjoys a reputation in treatment of AR, which has been supported by evidence-based medicine and recommended by guidelines. While treating local symptoms of AR, TCM regulates the psychosomatic conditions, which facilitates chronic disease management and long-term follow-up. We should integrate the advantages of TCM and western medicine, give full play to the unique nonnegligible and irreplaceable advantages of TCM, formulate a comprehensive diagnosis and treatment scheme for learning and promotion, and summarize the research outcomes to promote the theoretical innovation of TCM on AR from the perspective of integrated traditional Chinese and western medicine.


Result Analysis
Print
Save
E-mail