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.Influencing factors for failed cardiopulmonary resuscitation in patients with respiratory and cardiac arrest
Xiting DANG ; Jun YU ; Huini FU ; Shuzhen WANG ; Qiaoling ZHANG
Journal of Clinical Medicine in Practice 2025;29(11):100-104
Objective To investigate influencing factors for failed cardiopulmonary resuscitation(CPR)in patients with respiratory and cardiac arrest.Methods A retrospective analysis was con-ducted on the clinical data of 204 patients with respiratory and cardiac arrest.All patients underwent CPR treatment and were divided into success group and failure group based on the CPR outcome.A matched case-control study based on matching design was carried out.The success and failure groups were matched at a ratio of 1 to 2 using gender,age,body mass index(BMI),and the presence or absence of hypertension,hyperlipidemia,and diabetes as covariates.Logistic regression analysis was employed to explore the influencing factors for failed CPR in patients with respiratory and cardiac ar-rest.Results Among the 204 patients,65(31.86%)had successful CPR and were included in success group,while 139(68.14%)had failed CPR and were included in failure group.After a rati-o of 1 to 2 matching design,62 patients in the success group and 124 patients in the failure group were finally included in the study.Multivariate logistic regression analysis revealed that cardiovascular disease as the cause of respiratory and cardiac arrest,CPR performed outside the hospital,a long time interval from the onset of the condition to the initiation of CPR,and a large dose of epinephrine were independent risk factors for failed CPR(P<0.05).In contrast,the combined use of a bag-mask de-vice and endotracheal intubation during respiratory and cardiac arrest,a prolonged duration of CPR,and electrical defibrillation were independent protective factors for successful CPR(P<0.05).Con-clusion Cardiovascular disease,out-of-hospital CPR,a long time interval from the onset of the condi-tion to the initiation of CPR,and a large dose of epinephrine are risk factors for failed CPR in patients with respiratory and cardiac arrest.The combined use of a bag-mask device and endotracheal intubation during respiratory and cardiac arrest,prolonging the duration of CPR,and electrical defibrillation are protective factors for successful CPR.The matched case-control study method based on a matc-hing design can reduce the interference of confounding factors,ensure the reliability of the results,and provide a reliable basis for the formulation of CPR intervention protocols.
4.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.
5.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.
6.Application of Micro-CT in experimental animal disease models
Shuzhen LI ; Wenjing DAI ; Qingqing YU ; Miao TIAN ; Qian ZHANG ; Bei LI
Acta Laboratorium Animalis Scientia Sinica 2024;32(5):676-682
Micro-computed tomography(Micro-CT)is a non-invasive technology that is widely used in animal experiments to assist in the detection of bone,lung,oral,metabolic,middle and inner ear diseases,as well as tumors,and in other animal disease models.The technique can provide diverse scientific and reliable imaging data for animal experiments and has accordingly become an indispensable experimental method in animal experiments.In this review,we introduce the imaging principles of Micro-CT,review its application in the study of animal disease models,summarize the limitations of Micro-CT technology,and consider its future prospects.
7.Value of preoperative vascular ultrasound parameters in predicting postoperative lower extremity deep venous thrombosis in patients with gynecological malignant tumors
Wenhui GAO ; Weiwei ZHANG ; Nirong WANG ; Jiaqi ZHANG ; Jinghua DAI ; Xinhui LI ; Jian-Feng WEI ; Shuzhen YU
Chinese Journal of Anesthesiology 2024;44(8):937-940
Objective:To evaluate the value of preoperative vascular ultrasound parameters in predicting the postoperative lower extremity deep venous thrombosis (DVT) in patients with gynecological malignant tumors.Methods:Ninety-nine patients with gynecological malignant tumors, aged>18 yr, with body mass index<30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were selected. Vascular ultrasound examination was performed before surgery. The flow velocity and diameter of common femoral vein (CFV), deep femoral vein (DFV), popliteal vein (POV), and intermuscular vein (IMV) were recorded. Ultrasound examination of lower limb veins (including anterior tibial vein, posterior tibial vein, IMV, CFV, DFV, POV) were conducted at 1-8 days after surgery to determine whether a DVT occurred. The receiver operating charcateristic curve was used to evaluate the accuracy of each indicator in predicting the lower extremity DVT, and the cut-off value was determined based on the maximum principle of Jorden index. Results:The incidence of lower extremity DVT was 13.1%. The area under the curve (95% confidence interval) of the preoperative CFV flow velocity and diameter, DFV flow velocity and diameter, POV flow velocity and diameter, IMV flow velocity and diameter in predicting the lower extremity DVT were 0.769 (0.616-0.923) and 0.800 (0.644-0.950), 0.797 (0.641-0.954) and 0.771 (0.596-0.945), 0.806 (0.645-0.968) and 0.754 (0.606-0.903), 0.764 (0.615-0.914) and 0.818 (0.645-0.990), respectively ( P<0.05), and the predicted cut-off values were 27.13 cm/s and 11.93 mm, 19.31 cm/s and 10.15 mm, 16.04 cm/s and 8.79 mm, 14.39 cm/s and 8.68 mm, respectively, and the sensitivity and specificity were 90.0%, 71.4% and 90.0%, 74.3%; 90.0%, 74.3% and 90.0%, 68.6%; 90.0%, 82.9% and 90.0%, 72.9%; 90.0%, 70.0% and 80.0%, 87.1%, respectively. Conclusions:Preoperative vascular vascular ultrasound parameters can accurately predict the occurrence of postoperative lower extremity DVT in patients with gynecological malignant tumors.
8.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.
9.Accuracy of bedside lung ultrasound in predicting postoperative pulmonary complications in patients undergoing radical resection of gastrointestinal cancer
Jianmin JING ; Weiwei ZHANG ; Zhiqiang FANG ; Nirong WANG ; Yuehong QI ; Yan CHENG ; Jiaqi ZHANG ; Ying XUE ; Shuzhen YU
Chinese Journal of Anesthesiology 2023;43(8):937-941
Objective:To evaluate the accuracy of bedside lung ultrasound in predicting postoperative pulmonary complications (PPCs) in the patients undergoing radical resection of gastrointestinal cancer.Methods:One hundred and eight patients of both sexes, aged >18 yr, undergoing elective radical resection of gastrointestinal cancer with general anesthesia, were enrolled in the study. Lung ultrasound was performed before surgery (T 1) and at 2, 4 and 7 days after surgery (T 2-4). Lung ultrasound score (LUS) and B-line score were recorded. Serum procalcitonin (PCT) concentrations and blood routine were recorded, and systemic immune-inflammatory index (SII) was calculated. All the patients underwent chest CT examination before surgery and 7 days after surgery. The results of chest CT and clinical diagnosis were used as the gold standard for PPCs. The occurrence of PPCs within 7 days after surgery was recorded. The patients were divided into PPCs group and non-PPCs group according to the development of PPCs. Spearman′s correlation analysis was used to analyze the correlation of B-line score and LUS with PPCs, PCT and SII. The receiver operating curve was used to evaluate the accuracy of B-line score and LUB in predicting PPCs. Results:One hundred and three patients were finally enrolled in the study, including 45 patients in PPCs group and 58 patients in non-PPCs group, and the incidence of PPCs was 43.7%. Both B-line score and LUS were positively correlated with PPCs at T 1 ( P<0.001), and B-line score and LUS were positively correlated with PCT and SII at T 2-4 ( P<0.001). The AUC (95% confidence interval) of B-line score and LUB in predicting PPCs were 0.926 (0.879-0.972) and 0.909 (0.852-0.965), respectively ( P<0.001), the best cut-off values of B-line score and LUB in predicting PPCs were set at 25.5 and 11.5 respectively, and the sensitivity and specificity of B-line score were 0.80 and 0.88 respectively, and the sensitivity and specificity of LUB were 0.78 and 0.93 respectively. Conclusions:Bedside pulmonary ultrasonography (B-line score and LUS) can accurately predict the occurrence of PPCs in the patients undergoing radical resection of gastrointestinal cancer and dynamically evaluate the condition of PPCs, and B-line score >25.5 and LUS score >11.5 indicate a high risk of PPCs.
10.Accuracy of ultrasound measurement of airway parameters in predicting difficult mask ventilation
Jiaqi ZHANG ; Weiwei ZHANG ; Hao GUO ; Ying XUE ; Jianhui GAO ; Yaoyao QIN ; Nirong WANG ; Shuzhen YU
Chinese Journal of Anesthesiology 2023;43(10):1210-1213
Objective:To evaluate the accuracy of ultrasound measurement of airway parameters in predicting difficult mask ventilation (DMV).Methods:Ninety-six patients, aged 18-90 yr, with body mass index of 16-39 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective endotracheal intubation under general anesthesia, were included in this study. Clinical airway evaluation was performed at 1 day before surgery, and modified Mallampati classification, thyromental distance and rating of the upper lip bite test were recorded. At 30 min before anesthesia induction, mandibular condylar motion, tongue longitudinal cross-sectional area and transverse diameter of tongue were measured by ultrasound, and the tongue volume (product of tongue longitudinal cross-sectional area and transverse diameter of tongue) was calculated. Mask ventilation was performed after induction of anesthesia, mask ventilation difficulty grade ≥Ⅲ was defined as DMV, the patients were divided into 2 groups according to whether DMV occurred: non-DMV group (NDMV group) and DMV group. Correlations between the clinical airway evaluation indexes and ultrasonic airway parameters with statistically significant differences between groups and DMV were assessed using Spearman′s rank correlation. The area under the receiver operating characteristics curve was used to evaluate the accuracy of each parameter in predicting DMV, the critical value was determined, and the accuracy, sensitivity, specificity, positive and negative predictive values were calculated. Results:The modified Mallampati classification, rating of the upper lip bite test, ultrasonic tongue longitudinal cross-sectional area, transverse diameter of tongue and tongue volume were positively correlated with DMV, and thyromental distance and mandibular condylar motion were negatively correlated with DMV ( P<0.05). The area under the receiver operating characteristics curve of mandibular condylar motion and tongue volume in predicting DMV were 0.898 and 0.862, respectively, the cut-off values were 1.19 cm and 99.94 cm 3, respectively, and the sensitivity and specificity were all over 70% and 90%, respectively, the positive predictive values were 92.31% and 88.46%, respectively. Conclusions:Ultrasonic measurements of mandibular condylar motion and tongue volume can accurately predict DMV.


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