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.Differential Analysis of Heart Rate Variability in Repeated Continuous Performance Tests Among Healthy Young Men
Chung-Chih HSU ; Tien-Yu CHEN ; Jia-Yi LI ; Terry B. J. KUO ; Cheryl C. H. YANG
Psychiatry Investigation 2025;22(2):148-155
Objective:
Executive function correlates with the parasympathetic nervous system (PNS) based on static heart rate variability (HRV) measurements. Our study advances this understanding by employing dynamic assessments of the PNS to explore and quantify its relationship with inhibitory control (IC).
Methods:
We recruited 31 men aged 20–35 years. We monitored their electrocardiogram (ECG) signals during the administration of the Conners’ Continuous Performance Test-II (CCPT-II) on a weekly basis over 2 weeks. HRV analysis was performed on ECG-derived RR intervals using 5-minute windows, each overlapping for the next 4 minutes to establish 1-minute intervals. For each time window, the HRV metrics extracted were: mean RR intervals, standard deviation of NN intervals (SDNN), low-frequency power with logarithm (lnLF), and high-frequency power with logarithm (lnHF). Each value was correlated with detectability and compared to the corresponding baseline value at t0.
Results:
Compared with the baseline level, SDNN and lnLF showed marked decreases during CCPT-II. The mean values of HRV showed significant correlation with d’, including mean SDNN (R=0.474, p=0.012), mean lnLF (R=0.390, p=0.045), and mean lnHF (R=0.400, p=0.032). In the 14th time window, the significant correlations included SDNN (R=0.578, p=0.002), lnLF (R=0.493, p=0.012), and lnHF (R=0.432, p=0.031). Significant correlation between d’ and HRV parameters emerged only during the initial CCPT-II.
Conclusion
A significant correlation between PNS and IC was observed in the first session alone. The IC in the repeated CCPT-II needs to consider the broader neural network.
3.Differential Analysis of Heart Rate Variability in Repeated Continuous Performance Tests Among Healthy Young Men
Chung-Chih HSU ; Tien-Yu CHEN ; Jia-Yi LI ; Terry B. J. KUO ; Cheryl C. H. YANG
Psychiatry Investigation 2025;22(2):148-155
Objective:
Executive function correlates with the parasympathetic nervous system (PNS) based on static heart rate variability (HRV) measurements. Our study advances this understanding by employing dynamic assessments of the PNS to explore and quantify its relationship with inhibitory control (IC).
Methods:
We recruited 31 men aged 20–35 years. We monitored their electrocardiogram (ECG) signals during the administration of the Conners’ Continuous Performance Test-II (CCPT-II) on a weekly basis over 2 weeks. HRV analysis was performed on ECG-derived RR intervals using 5-minute windows, each overlapping for the next 4 minutes to establish 1-minute intervals. For each time window, the HRV metrics extracted were: mean RR intervals, standard deviation of NN intervals (SDNN), low-frequency power with logarithm (lnLF), and high-frequency power with logarithm (lnHF). Each value was correlated with detectability and compared to the corresponding baseline value at t0.
Results:
Compared with the baseline level, SDNN and lnLF showed marked decreases during CCPT-II. The mean values of HRV showed significant correlation with d’, including mean SDNN (R=0.474, p=0.012), mean lnLF (R=0.390, p=0.045), and mean lnHF (R=0.400, p=0.032). In the 14th time window, the significant correlations included SDNN (R=0.578, p=0.002), lnLF (R=0.493, p=0.012), and lnHF (R=0.432, p=0.031). Significant correlation between d’ and HRV parameters emerged only during the initial CCPT-II.
Conclusion
A significant correlation between PNS and IC was observed in the first session alone. The IC in the repeated CCPT-II needs to consider the broader neural network.
4.Differential Analysis of Heart Rate Variability in Repeated Continuous Performance Tests Among Healthy Young Men
Chung-Chih HSU ; Tien-Yu CHEN ; Jia-Yi LI ; Terry B. J. KUO ; Cheryl C. H. YANG
Psychiatry Investigation 2025;22(2):148-155
Objective:
Executive function correlates with the parasympathetic nervous system (PNS) based on static heart rate variability (HRV) measurements. Our study advances this understanding by employing dynamic assessments of the PNS to explore and quantify its relationship with inhibitory control (IC).
Methods:
We recruited 31 men aged 20–35 years. We monitored their electrocardiogram (ECG) signals during the administration of the Conners’ Continuous Performance Test-II (CCPT-II) on a weekly basis over 2 weeks. HRV analysis was performed on ECG-derived RR intervals using 5-minute windows, each overlapping for the next 4 minutes to establish 1-minute intervals. For each time window, the HRV metrics extracted were: mean RR intervals, standard deviation of NN intervals (SDNN), low-frequency power with logarithm (lnLF), and high-frequency power with logarithm (lnHF). Each value was correlated with detectability and compared to the corresponding baseline value at t0.
Results:
Compared with the baseline level, SDNN and lnLF showed marked decreases during CCPT-II. The mean values of HRV showed significant correlation with d’, including mean SDNN (R=0.474, p=0.012), mean lnLF (R=0.390, p=0.045), and mean lnHF (R=0.400, p=0.032). In the 14th time window, the significant correlations included SDNN (R=0.578, p=0.002), lnLF (R=0.493, p=0.012), and lnHF (R=0.432, p=0.031). Significant correlation between d’ and HRV parameters emerged only during the initial CCPT-II.
Conclusion
A significant correlation between PNS and IC was observed in the first session alone. The IC in the repeated CCPT-II needs to consider the broader neural network.
5.Differential Analysis of Heart Rate Variability in Repeated Continuous Performance Tests Among Healthy Young Men
Chung-Chih HSU ; Tien-Yu CHEN ; Jia-Yi LI ; Terry B. J. KUO ; Cheryl C. H. YANG
Psychiatry Investigation 2025;22(2):148-155
Objective:
Executive function correlates with the parasympathetic nervous system (PNS) based on static heart rate variability (HRV) measurements. Our study advances this understanding by employing dynamic assessments of the PNS to explore and quantify its relationship with inhibitory control (IC).
Methods:
We recruited 31 men aged 20–35 years. We monitored their electrocardiogram (ECG) signals during the administration of the Conners’ Continuous Performance Test-II (CCPT-II) on a weekly basis over 2 weeks. HRV analysis was performed on ECG-derived RR intervals using 5-minute windows, each overlapping for the next 4 minutes to establish 1-minute intervals. For each time window, the HRV metrics extracted were: mean RR intervals, standard deviation of NN intervals (SDNN), low-frequency power with logarithm (lnLF), and high-frequency power with logarithm (lnHF). Each value was correlated with detectability and compared to the corresponding baseline value at t0.
Results:
Compared with the baseline level, SDNN and lnLF showed marked decreases during CCPT-II. The mean values of HRV showed significant correlation with d’, including mean SDNN (R=0.474, p=0.012), mean lnLF (R=0.390, p=0.045), and mean lnHF (R=0.400, p=0.032). In the 14th time window, the significant correlations included SDNN (R=0.578, p=0.002), lnLF (R=0.493, p=0.012), and lnHF (R=0.432, p=0.031). Significant correlation between d’ and HRV parameters emerged only during the initial CCPT-II.
Conclusion
A significant correlation between PNS and IC was observed in the first session alone. The IC in the repeated CCPT-II needs to consider the broader neural network.
6.Differential Analysis of Heart Rate Variability in Repeated Continuous Performance Tests Among Healthy Young Men
Chung-Chih HSU ; Tien-Yu CHEN ; Jia-Yi LI ; Terry B. J. KUO ; Cheryl C. H. YANG
Psychiatry Investigation 2025;22(2):148-155
Objective:
Executive function correlates with the parasympathetic nervous system (PNS) based on static heart rate variability (HRV) measurements. Our study advances this understanding by employing dynamic assessments of the PNS to explore and quantify its relationship with inhibitory control (IC).
Methods:
We recruited 31 men aged 20–35 years. We monitored their electrocardiogram (ECG) signals during the administration of the Conners’ Continuous Performance Test-II (CCPT-II) on a weekly basis over 2 weeks. HRV analysis was performed on ECG-derived RR intervals using 5-minute windows, each overlapping for the next 4 minutes to establish 1-minute intervals. For each time window, the HRV metrics extracted were: mean RR intervals, standard deviation of NN intervals (SDNN), low-frequency power with logarithm (lnLF), and high-frequency power with logarithm (lnHF). Each value was correlated with detectability and compared to the corresponding baseline value at t0.
Results:
Compared with the baseline level, SDNN and lnLF showed marked decreases during CCPT-II. The mean values of HRV showed significant correlation with d’, including mean SDNN (R=0.474, p=0.012), mean lnLF (R=0.390, p=0.045), and mean lnHF (R=0.400, p=0.032). In the 14th time window, the significant correlations included SDNN (R=0.578, p=0.002), lnLF (R=0.493, p=0.012), and lnHF (R=0.432, p=0.031). Significant correlation between d’ and HRV parameters emerged only during the initial CCPT-II.
Conclusion
A significant correlation between PNS and IC was observed in the first session alone. The IC in the repeated CCPT-II needs to consider the broader neural network.
7.A Study on the In Vitro Antibacterial Effects of Colistin or Tigecycline Combined with Three Antimicrobial Agents Against Carbapenem-resistant Acinetobacter Baumannii
Weichen HUANG ; Kuo LI ; Lijing GUO ; Xinyi JIN ; Chaogui TANG ; Ning LIN ; Jingjing HUANG
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1131-1137
To analyze the Non-duplicate CRAB strains isolated from clinical specimens between June and December 2023 at Huai'an First People's Hospital Affiliated to Nanjing Medical University were retrospectively collected. The minimum inhibitory concentrations of commonly used antimicrobial agents against these strains were determined using the broth microdilution method. A total of 48 CRAB strains were included. COL-based combination regimens all exhibited favorable synergistic or additive effects against CRAB. Among them, the COL+IPM group showed the highest synergistic rate (83.3%), while the COL+AMK and COL+CSL groups primarily demonstrated additive effects (additive rates of 66.7% and 70.8%, respectively). TGC-based combination regimens mainly exhibited additive or indifferent effects, with the TGC+CSL group showing the highest additive rate (75.0%) and the TGC+AMK group showing the highest indifferent rate (70.8%). No antagonistic effects were observed in any of the six combination regimens. Further analysis revealed that the antibacterial effect of the COL+IPM group against CRAB was significantly different from that of the other combination regimens ( The combination of COL and IPM demonstrates the optimal synergistic antibacterial effect against CRAB, with the highest synergistic rate, and can be used as an empirical combination regimen for the clinical treatment of CRAB infections.
8.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.
9.Expression of CRKL in intrahepatic cholangiocarcinoma and its effect on the proliferation and invasion of cholangiocarci-noma cells
Wen-Lei KUO ; Xin-Yue BAO ; Jing-Bo CHANG ; Qi SUN ; Li-Min WEI
Chinese Journal of Current Advances in General Surgery 2024;27(9):684-688
Objective:To investigate the expression of kinase-like gene CT10 regulatory fac-tor(CRKL)in intrahepatic cholangiocarcinoma(ICC)and its effect on the proliferation and invasion of intrahepatic cholangiocarcinoma cells.Methods:qRT-PCR detected CRKL transcription in ICC pa-tient tissues and adjacent tissues.Immunohistochemistry assessed CRKL expression in ICC tissues and adjacent tissues,and analyzed its relationship with clinicopathological features.For the inhibition of CRKL expression in QBC939 cells by siRNA technology,the effect of CRKL silencing on AKT and ERK signaling pathway was measured by Western blot.CRKL's influence on QBC939 cell prolifera-tion and invasion was analyzed by MTT,clonogenesis,and Transwell assays.Results:The expres-sion of CRKL in ICC tissues was up-regulated,and there were statistically significant differences in CRKL expression in ICC with different clinicopathological features such as tumor size,lymph node metastasis and TNM stage.Cellular experiments showed a significant decrease in the phosphoryla-tion of AKT and ERK upon inhibition of CRKL,and the proliferation and invasion ability of ICC cells was significantly diminished(P<0.05).Conclusion:CRKL promotes ICC cell proliferation and invasion through AKT and ERK pathways,offering new molecular targets and directions for targeted therapy.
10.The latent patterns and characteristics of smartphone addiction among college students
Lei ZHANG ; Xue LI ; Kuo CHANG ; Hui ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(8):742-748
Objective:To explore the latent patterns of smartphone addiction among college students and their characteristics of psychology and smartphone usage.Methods:In July 2023, a cross-sectional investigation was conducted among 206 college students in Beijing by using self-designed basic information questionnaire, patient health questionnaire (PHQ-9), the short-form of the UCLA loneliness scale (ULS-8), interaction anxiety scale(IAS), fear of missing out scale (FOMOs), ruminative response scale(RRS), the short form version of boredom proneness scale (BPS-SF), a sub-scale on effortful control from the early adolescent temperament measure, and the short version of smartphone addiction scale (SAS-SV), and data of weekly smartphone usage time and frequency were collected as well. SPSS 25.0 software was used for statistical description and inter group comparison.Cluster analysis was performed using Python 3.8 software K-means algorithm.The random forest algorithm was used to evaluate the importance of influencing factors in different categories.Results:(1) Smartphone addiction (41.00 (31.00, 47.00)) was positively correlated with depression(6.00 (2.00, 12.00)), loneliness (15.00 (11.00, 20.00)), social anxiety (46.00 (32.75, 54.00)), fear of missing out (21.00 (16.00, 28.00)), rumination (26.00 (22.00, 29.00)), boredom proneness (41.50 (32.00, 49.25)), average daily smartphone usage time ((513.30±213.29) min) and average time per smartphone use (6.60 (3.68, 14.09)) ( r=0.163~0.626, all P<0.05), while negatively correlated with effortful control (49.00 (44.00, 59.00)) ( r=-0.613, P<0.01). (2) Cluster analysis showed that there were three latent patterns of smartphone addiction among college students: non-addicted group (32.04%, 66/206), boredom-based smartphone addiction group (26.70%, 55/206), and multi-risk smartphone addiction group (41.26%, 85/206). (3) Significant differences were found among the different latent patterns in terms of depression, loneliness, social anxiety, rumination, boredom proneness, effortful control, smartphone addiction ( H=138.805, 127.342, 112.149, 88.069, 72.146, 100.206, 115.159, 114.926, all P<0.001), as well as average daily smartphone usage time and frequency, average smartphone usage time each time ( F/ H=7.548, 9.332, 16.086; all P<0.01). (4) Random forest algorithm analysis results showed that the top three feature importance rankings for the non-addicted group were effortful control, social anxiety, fear of missing out, with feature importance values of 0.33, 0.23 and 0.15. The top three feature importance rankings for the boredom-based smartphone addiction group were boredom proneness, fear of missing out, loneliness, with feature importance values of 0.35, 0.20 and 0.15. The top three feature importance rankings for the multi-risk smartphone addiction group were fear of missing out, rumination, boredom proneness, with feature importance values of 0.29, 0.19 and 0.17, respectively. Conclusions:There are three latent patterns of smartphone addiction among college students, and significant differences exist among these patterns in different psychology factors and characteristic of smartphone usage. In the future, targeted psychological interventions can be implemented based on the characteristics of different patterns of college students.


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