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.Application of dual fluorescence laparoscopy in the repair of complex ureteral stricture with lingual mucosa graft
Yuancheng ZHOU ; Chaoqi LIANG ; Shuaishuai CHAI ; Ruoyu LI ; Nana LI ; Zhaotai GU ; Xingyuan XIAO ; Bing LI
Journal of Modern Urology 2025;30(3):227-231
Objective: To evaluate the feasibility and effectiveness of dual fluorescence laparoscopy in the localization of ureteral stricture and its blood supply,and to provide a new idea for the treatment of complex ureteral stenosis,thus helping doctors to improve the efficiency of ureteral reconstruction surgery. Methods: Our team developed a dual fluorescence laparoscopic system,which could simultaneously identify the ureter stricture by intra-ureteral injection of methylene blue (MB) and assess the blood supply of the ureteral stumps by intravenous injection of indocyanine green (ICG). Results: The clinical data of 3 patients who underwent lingual mucosa ureteroplasty using dual fluorescence laparoscopy in Zhongnan Hospital of Wuhan University were retrospectively analyzed.All operations were successful,without conversion to open surgery.The operation time was 144,132 and 163 minutes,respectively.The length of harvested lingual mucosa graft was 2.0,2.8 and 3.5 cm,respectively.No intraoperative or postoperative complications occurred.Eight weeks after operation,ureterography showed that the ureter was unobstructed. Conclusion: Dual fluorescence laparoscopy is safe and feasible in the repair of complex ureteral stricture with lingual mucosa graft,which provides a new idea for complex ureteral reconstruction.
3.Plasma and hepatic free fatty acid, tricarboxylic acid cycle, and ketone bodies metabolic profiles in progressive Gao-Binge model
Anqin LI ; Luxin PANG ; Yuanyuan CHAI ; Qinwei YU ; Zhenzhou JIANG ; Luyong WANG
Journal of China Pharmaceutical University 2025;56(2):196-206
To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.
4.Challenges and optimization strategies for radiation exposure in pediatric patients during total-body PET/CT examinations
Wenhui LIU ; Yulin GUO ; Yinuo SUN ; Leiying CHAI ; Yudong JING ; Kun LI
Chinese Journal of Radiological Health 2025;34(4):602-606
Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.
5.Clinical efficacy of fecal microbiota transplantation based on syndrome element differentiation principle in the treatment of type 2 diabetes mellitus
Ruiting Chai ; Jinwen Shi ; Fangzhen Wu ; Zhaoyang Yang ; Candong Li
Digital Chinese Medicine 2025;8(3):363-378
Objective:
To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation (FMT) in patients with type 2 diabetes mellitus (T2DM), and to preliminarily identify the traditional Chinese medicine (TCM) syndrome element characteristics of FMT in the treatment of T2DM.
Methods:
Between March 25, 2023 and September 30, 2024, T2DM patients who met the inclusion and exclusion criteria were enrolled at the Department of Rheumatology and Endocrinology of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine. Participants received oral microbiota capsules as an adjunct to metformin therapy. Information obtained by four diagnostic methods of TCM, along with clinical and laboratory parameters, was collected before and after the intervention. Metagenomic sequencing was employed to analyze the gut microbiota, and Spearman correlation analysis was used to explore the relationship between laboratory indicators and differential bacterial genera. According to the post-treatment reduction in glycosylated hemoglobin (HbA1c), patients were categorized into a response (R) group and a non-response (NR) group. Treatment outcomes, safety indicators, gut microbiota changes, and TCM syndrome element features were compared between the two groups.
Results:
A total of 53 T2DM patients were included in the final analysis, and 30 patients were assigned to R group and 23 to NR group. After treatment, the R group exhibited significant reductions in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (2hPG) (P < 0.05 or P < 0.01). The NR group also showed significant decreases in HbA1c and FPG levels P < 0.01 or P < 0.05. Compared with the NR group, after treatment, FPG level in the R group demonstrated significant reductions (P < 0.01). As compared with before treatment, pancreatic islet function demonstrated enhancement in the R group, a significant increase in the 2-hour pastprandial C-peptide (2hC-P) levels in R group (P < 0.05), whereas no marked change was observed in the NR group. Regarding body composition indicators, the R group showed significantly lower waist-hip ratio (WHR), visceral fat (VF), and subcutaneous fat (SF) levels compared with the NR group (P < 0.01). After treatment, the NR group exhibited a significant elevation in aspartate aminotransferase (AST) levels (P < 0.05). Other safety-related indicators fluctuated within normal reference ranges, and no other adverse events, such as diarrhea, fever, or nausea, were reported. Metagenomic sequencing showed that FMT improved the diversity and richness of the gut microbiota, remodeling its overall structure. At the phylum level, the abundance of p_Firmicutes decreased significantly (P < 0.01), while the abundances of p_Bacteroidota and p_Proteobacteria increased significantly (P < 0.01). At the family level, among the 125 identified taxa, the abundances of f_Bacteroidaceae, f_Lactobacillaceae, and f_Sutterellaceae were significantly elevated, whereas six families, including f_Lachnospiraceae, f_Ruminococcaceae, and f_Coriobacteriaceae, were significantly decreased (all P < 0.05). Among the 367 taxa at the genus level, the top 10 differential genera showed significantly increased abundances of g_Bacteroides and g_Sutterella, and significantly decreased abundances in eight genera, including g_Faecalibacterium, g_Ruminococcus, g_Blautia, and g_Collinsella (all P < 0.05). Correlation analysis suggested that the phylum p_Bacillota was positively correlated with improvements in T2DM laboratory parameters, g_norank_f_Prevotellaceae was significantly positively correlated with fasting C-peptide (FC-P) and 2hC-P (P < 0.05). HbA1c demonstrated a significantly positive correlation with g_Blautia and g_Gemmiger (P < 0.05) and a significantly negative correlation with g_Bacteroides and g_Collinsella (P > 0.05). Analysis of syndrome element characteristics revealed that the R group was primarily characterized by pathological patterns of dampness, phlegm, and Yang deficiency. Before treatment, statistically significant reductions in syndrome element scores were observed for dampness, Yang deficiency, spleen, phlegm, Qi deficiency, Qi stagnation, and Yin deficiency (P < 0.01), as well as for heat and liver (P < 0.05). The NR group was mainly featured with Qi deficiency and Yin deficiency. Statistically significant changes in their syndrome element scores after treatment were noted for Qi deficiency (P < 0.01), and for spleen, Qi stagnation, liver, and blood deficiency (P < 0.05). In this group, the score changes for Yang deficiency, Yin deficiency, heat, and dampness were not statistically significant (P > 0.05).
Conclusion
The principles of syndrome element differentiation can be effectively applied to predict treatment efficacy and facilitate patient selection for FMT in the treatment of T2DM. Patients with T2DM presented with specific TCM syndrome element characteristics, notably dampness, phlegm, and Yang deficiency, represent a highly responsive population to FMT therapy.
6.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.
7.Association between inflammatory cytokines and premature ovarian insufficiency: a bidirectional Mendelian randomization study
GAO Zengjie ; KONG Xiangyan ; LI Lailai ; CHAI Yihui
Journal of Preventive Medicine 2025;37(5):512-516,520
Objective:
To examine the causal relationship between inflammatory cytokines and premature ovarian insufficiency (POI) using bidirectional Mendelian randomization (MR) approach, so as to provide the basis for the prevention and treatment of POI.
Methods:
The data for 91 inflammatory cytokines were sourced from the IEU OpenGWAS database, comprising 14 824 participants. GWAS data for POI were sourced from the FinnGen database, including 118 484 individuals (among which 254 were POI cases). MR analysis was performed using the inverse variance weighted (IVW) method with inflammatory cytokines as exposure and POI as the outcome for forward MR analysis and POI as the exposure and inflammatory cytokines as outcome for reverse MR analysis. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, and the MR-PRESSO test.
Results:
Forward MR analysis demonstrated statistically significant associations between POI and interleukin-10 (OR=0.410, 95%CI: 0.233-0.721), interleukin-33 (OR=2.826, 95%CI: 1.228-6.504), C-C motif chemokine ligand 19 (OR=0.583, 95%CI: 0.364-0.932), monocyte chemoattractant protein-3 (OR=0.559, 95%CI: 0.335-0.936), interleukin-18 receptor 1 (OR=1.370, 95%CI: 1.030-1.821), and interleukin-13 (OR=1.990, 95%CI: 1.034-3.832). Reverse MR analysis revealed significant negative associations between POI and 15 inflammatory cytokines, including C-C motif chemokine ligand 23 (OR=0.981, 95%CI: 0.968-0.994) and axin-1 (OR=0.978, 95%CI: 0.963-0.994). Sensitivity analysis showed no evidence of heterogeneity or horizontal pleiotropy (all P>0.05).
Conclusion
Elevated levels of interleukin-33, interleukin-18 receptor 1 and interleukin-13 were associated with an increased risk of POI, while POI may be associated with decreased levels of 15 inflammatory cytokines including C-C motif chemokine ligand 23 and axin-1.
8.Rules on acupoint selection and treatment for epigastric pain based on the data mining of ancient acupuncture-moxibustion prescriptions.
Suyun LI ; Jianing WANG ; Zhongnan LI ; Qingyang CHAI ; Xianghong JING
Chinese Acupuncture & Moxibustion 2025;45(2):253-261
The rules of acupoint selection and treatment were identified and discovered from the collected ancient acupuncture-moxibustion prescriptions recorded the earliest for epigastric pain. The database of ancient acupuncture-moxibustion prescriptions for epigastric pain was set up using Excel2016 software. After the disease term, etiology, pathogenesis, symptoms and acupoints were normalized, the underlying multi-dimensional correlation among the elements of acupuncture-moxibustion was explored, using the frequency statistics and the association rule of Apriori algorithm. In the ancient time, in treatment with acupuncture-moxibustion therapy for epigastric pain, the acupoints of the high use frequency were sequenced as Zhongwan (CV12), Shangwan (CV13), Zusanli (ST36), Neiguan (PC6), Gongsun (SP4), Pishu (BL20) and Weishu (BL21). The common combinations of acupoints included the pairs of back-shu points, the combination of back-shu points and front-mu points, the combination of front-mu points and yuan-source points and the combination of back-shu points and the lower he-sea points. The highly involved acupoints were those from the conception vessel, pericardium meridian, spleen meridian, stomach meridian and bladder meridian; and they were commonly distributed on the abdomen, the yin parts of the foot and the arm, the yang part of the leg and on the back. Regarding the etiologies such as parasites, food retention, masses, qi stagnation and stomach cold, Zhongwan (CV12) and Shangwan (CV13) were coordinated; and Sanyinjiao (SP6) and Daling (PC7) were highly associated with masses. Besides cold injury, parasites and masses, for the epigastric pain caused by other factors of etiology (qi stagnation, stomach cold and food retention), moxibustion therapy was greatly applicable. For epigastric pain combined with qi reversion in the lower abdominal region, Qichong (ST30), Sanyinjiao (SP6), Tianshu (ST25) and Zusanli (ST36) must be selected. Dadu (SP2) and Taibai (SP3) must be used if the distention in the chest and abdomen accompanied; and Zhongzhu (TE3) be used if back pain involved. Zusanli (ST36) was commonly selected for hiccups. For the other accompanied symptoms, Zhongwan (CV12) was used, which is consistent with the acupoint selection of main symptoms. On the trunk, moxibustion was generally used at Weishu (BL21), Pishu (BL20), Geshu (BL17), Zhongwan (CV12), Juque (CV14) and Qihai (CV6), except Shangwan (CV13). Among the acupoints below the elbows and knees, moxibustion was commonly applicable at Zusanli (ST36), and acupuncture was often used at Gongsun (SP4) and Daling (PC7).
Acupuncture Points
;
Humans
;
Moxibustion/history*
;
History, Ancient
;
Acupuncture Therapy/history*
;
Data Mining
;
Abdominal Pain/history*
9.Patient-derived xenograft model: Applications and challenges in liver cancer.
Shuangshuang DOU ; Yunfei HUO ; Minghui GAO ; Quanwei LI ; Buxin KOU ; Mengyin CHAI ; Xiaoni LIU
Chinese Medical Journal 2025;138(11):1313-1323
Liver cancer is one of the most common malignant tumors worldwide. Currently, the available treatment methods cannot fully control its recurrence and mortality rate. Establishing appropriate animal models for liver cancer is crucial for developing new treatment technologies and strategies. The patient-derived xenograft (PDX) model preserves the tumor's microenvironment and heterogeneity, which makes it advantageous for biological research, drug evaluation, personalized medicine, and other purposes. This article reviews the development, preparation techniques, application fields, and challenges of PDX models in liver cancer, providing insights for the research and exploration of PDX models in diagnostic and therapeutic strategies of liver cancer.
Liver Neoplasms/drug therapy*
;
Animals
;
Humans
;
Xenograft Model Antitumor Assays/methods*
;
Mice
;
Disease Models, Animal
10.Chemical and pharmacological research progress on Mongolian folk medicine Syringa pinnatifolia.
Kun GAO ; Chang-Xin LIU ; Jia-Qi CHEN ; Jing-Jing SUN ; Xiao-Juan LI ; Zhi-Qiang HUANG ; Ye ZHANG ; Pei-Feng XUE ; Su-Yi-le CHEN ; Xin DONG ; Xing-Yun CHAI
China Journal of Chinese Materia Medica 2025;50(8):2080-2089
Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional
;
Humans
;
Drugs, Chinese Herbal/pharmacology*
;
Animals
;
Syringa/chemistry*


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