1.Mechanism of Buyang Huanwutang in Inhibiting Ferroptosis and Enhancing Neurological Function Recovery After Spinal Cord Injury via GPX4-ACSL4 Axis
Luchun XU ; Guozheng JIANG ; Yukun MA ; Jiawei SONG ; Yushan GAO ; Guanlong WANG ; Jiaojiao FAN ; Yongdong YANG ; Xing YU ; Xiangsheng TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):20-30
ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 (GPX4)-acyl-CoA synthetase long-chain family member 4 (ACSL4) axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury (SCI). MethodsNinety rats were randomly divided into five groups: sham operation group, model group, low-dose Buyang Huanwutang group (12.5 g·kg-1), high-dose Buyang Huanwutang group (25 g·kg-1), and Buyang Huanwutang + inhibitor group (25 g·kg-1 + 5 g·kg-1 RSL3). The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan (BBB) scale. Hematoxylin-eosin (HE), Nissl, and Luxol fast blue (LFB) staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein (MBP), GPX4, and ACSL4. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group, the model group exhibited significantly reduced BBB scores (P<0.01), severe pathological damage in spinal cord tissue, and marked mitochondrial ultrastructural disruption. In addition, the model group showed a decrease in the number of NeuN-positive cells (P<0.01), reduced fluorescence intensity of MBP and GPX4 (P<0.01), lower levels of GSH and SOD (P<0.01), and downregulated mRNA expression of GPX4 (P<0.01). Moreover, compared to the sham operation group, the model group had elevated levels of ROS, MDA, and tissue iron content (P<0.01), along with increased fluorescence intensity and mRNA expression of ACSL4 (P<0.01). Compared with the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group showed significantly improved BBB scores (P<0.05, P<0.01) and exhibited less severe spinal cord tissue damage, reduced edema and inflammatory cell infiltration, increased neuronal survival, and more intact myelin structures. Additionally, mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP (P<0.05, P<0.01). Furthermore, Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 (P<0.01) and decreased the fluorescence intensity and mRNA expression of ACSL4 (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. Finally, the Buyang Huanwutang group significantly decreased ROS, MDA, and tissue iron content (P<0.01) and significantly increased GSH and SOD levels (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis, reduces secondary neuronal and myelin injury and oxidative stress, and ultimately promotes the recovery of neurological function.
2.Triglyceride-glucose index and homocysteine in association with the risk of stroke in middle-aged and elderly diabetic populations
Xiaolin LIU ; Jin ZHANG ; Zhitao LI ; Xiaonan WANG ; Juzhong KE ; Kang WU ; Hua QIU ; Qingping LIU ; Jiahui SONG ; Jiaojiao GAO ; Yang LIU ; Qian XU ; Yi ZHOU ; Xiaonan RUAN
Shanghai Journal of Preventive Medicine 2025;37(6):515-520
ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹
3.Correlation between urinary protein levels and the incidence of chronic obstructive pulmonary disease in middle-aged and elderly population
Jiahui SONG ; Xiaonan WANG ; Qingping LIU ; Zhitao LI ; Kang WU ; Xiaolin LIU ; Jiaojiao GAO ; Juzhong KE ; Na WANG ; Chaowei FU ; Genming ZHAO ; Xiaonan RUAN
Journal of Public Health and Preventive Medicine 2024;35(4):11-15
Objective To explore the relationship between baseline urinary protein levels and the onset of chronic obstructive pulmonary disease (COPD). Methods A questionnaire survey, blood and urine sample collection, physical examination, and pulmonary function test were conducted among permanent residents over 40 years old in Pudong New Area, Shanghai. The subjects were divided into four groups based on the baseline urine albumin-to-creatinine ratio (ACR) quartiles (0~1.65 mg/g, 1.65~4.89 mg/g, 4.89~10.78 mg/g, and ≥10.78 mg/g). Cox regression analysis was used to explore the relationship between ACR levels and the incidence of COPD in middle-aged and elderly people. Results Among the 3 105 subjects, the median follow-up time was 3.212 years (P25~P75:3.102~3.473). 116 new cases of COPD were observed, with an incidence density of 10.423 per 1000 person-years. The incidence densities for COPD at four ACR levels were 7.922 per 1 000 person-years, 8.300 per 1 000 person-years , 11.419 per 1 000 person-years, and 13.843 per 1 000 person-years, respectively. Cox regression analysis revealed that as the ACR level increased, there was a rising trend in the incidence rate of COPD (χ2=4.396, P=0.036). After adjusting for gender, age, education level, occupational exposure to dust, history of childhood pneumonia, smoking, family history of COPD, central obesity, and hypertension, the risk of developing COPD was 2.499 times higher (95% CI: 1.460~4.276) for ACR levels ≥10.78 mg/g compared to the reference group with a baseline ACR level of 0~1.65 mg/g. Conclusion Elevated ACR levels in middle-aged and elderly population may increase the risk of COPD, and early monitoring of urine protein levels is beneficial for COPD prevention.
4.Investigation on Preventive Effect of Total Saponins of Notoginseng Radix et Rhizoma on Aspirin-induced Small Intestine Injury Based on Serum Metabolomics
Wenhui LIU ; Guodong HUA ; Baochen ZHU ; Ruoyu GAO ; Xin HUANG ; Meng WANG ; Zheng LIU ; Jiaojiao CHENG ; Zhibin SONG ; Jingui WANG ; Chunmiao XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):196-203
ObjectiveMetabolomics was utilized to investigate the preventive effect of notoginseng total saponins(NTS) on aspirin(acetyl salicylic acid, ASA)-induced small bowel injury in rats. MethodFifty male SD rats were randomly divided into normal and model groups, NTS high-dose and low-dose groups(62.5, 31.25 mg·kg-1), and positive drug group(omeprazole 2.08 mg·kg-1+rebamipide 31.25 mg·kg-1), with 10 rats in each group. Except for the normal group, rats in other groups were given ASA enteric-coated pellets 10.41 mg·kg-1 daily to establish a small intestine injury model. On this basis, each medication group was gavaged daily with the corresponding dose of drug, and the normal group and the model group were gavaged with an equal amount of drinking water. Changes in body mass and fecal characteristics of rats were recorded and scored during the period. After 14 weeks of administration, small intestinal tissues of each group were taken for hematoxylin-eosin(HE) staining, scanning electron microscopy to observe the damage, and the apparent damage of small intestine was scored. Serum from rats in the normal group, the model group, and the NTS high-dose group was taken and analyzed for metabolomics by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), and the data were processed by multivariate statistical analysis, the potential biomarkers were screened by variable importance in the projection(VIP) value≥1.0, fold change(FC)≥1.5 or ≤0.6 and t-test P<0.05, and pathway enrichment analysis of differential metabolites was performed in conjunction with Human Metabolome Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG). ResultAfter 14 weeks of administration, the average body mass gain of the model group was lower than that of the normal group, and the NTS high-dose group was close to that of the normal group. Compared with the normal group, the fecal character score of rats in the model group was significantly increased(P<0.05), and compared with the model group, the scores of the positive drug group and the NTS high-dose group were reduced, but the difference was not statistically significant. HE staining and scanning electron microscopy results showed that NTS could significantly improve ASA-induced small intestinal injury, compared with the normal group, the small bowel injury score of the model group was significantly increased(P<0.01), compared with the model group, the small bowel injury scores of the NTS low and high dose groups were significantly reduced(P<0.05, P<0.01). Serum metabolomics screened a total of 75 differential metabolites between the normal group and the model group, of which 55 were up-regulated and 20 were down-regulated, 76 differential metabolites between the model group and the NTS groups, of which 14 were up-regulated and 62 were down-regulated. NTS could modulate three differential metabolites(salicylic acid, 3-hydroxybenzoic acid and 4-hydroxybenzoic acid), which were involved in 3 metabolic pathways, namely, the bile secretion, the biosynthesis of folic acid, and the biosynthesis of phenylalanine, tyrosine and tryptophan. ConclusionNTS can prevent ASA-induced small bowel injury, and the underlying mechanism may be related to the regulation of bile secretion and amino acid metabolic pathways in rats.
5.Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury
Luchun Xu ; Yongdong Yang ; Guozheng Jiang ; Yushan Gao ; Jiawei Song ; Yukun Ma ; Jiaojiao Fan ; Guanlong Wang ; Xing Yu ; Xiangsheng Tang
Journal of Traditional Chinese Medical Sciences 2024;11(4):456-465
Objective:
To explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI).
Methods:
An acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer.
Results:
From postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < .05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < .05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < .05).
Conclusion
BYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.
6.Evaluation of the effect of meteorological risk forecasting service intervention on acute onset and medical expenses of patients with COPD in Pudong New Area of Shanghai
Zhitao LI ; Xiaonan WANG ; Xiaolin LIU ; Juzhong KE ; Yang LIU ; Chaowei FU ; Qingping LIU ; Jiaojiao GAO ; Jiahui SONG ; Kang WU ; Li PENG ; Xiaofang YE ; Xiaonan RUAN
Shanghai Journal of Preventive Medicine 2024;36(2):197-202
ObjectiveTo evaluate the intervention effect of meteorological risk forecasting service on acute onset and medical expenses of chronic obstructive pulmonary disease(COPD) patients, and to provide scientific basis for the establishment of health management model for chronic obstructive pulmonary disease(COPD) patients. MethodsStudy subjects were recruited from chronic obstructive pulmonary patients aged ≥40 in Pudong New Area. Propensity score matching method was used to determine the intervention group and the control group. The control group received regular health education and follow-up management, and the intervention group was provided with meteorological and environmental risk forecasting services through WeChat, mobile phone short message service(SMS)and telephone. Finally, a total of2 589 subjects were included in the analysis, including 1 300 in the intervention group and 1 289 in the control group. General demographic data, past medical history and family history of COPD, COPD related knowledge and practice survey, COPD related symptom assessment, acute onset, health service utilization and medical expenses before and after intervention were collected through questionnaire survey. The differences of acute attack, health service utilization and related medical expenses between the two groups before and after intervention were compared to evaluate the intervention effect. ResultsIn terms of acute attacks, after intervention, the incidence of acute attacks in the intervention group was lower than that before intervention(χ2=52.901, P<0.001), and the incidence of acute attacks in the groups with different intervention methods was lower than that before intervention (P<0.001). WeChat had the best effect, decreasing the incidence by 14.4%, followed by mobile phone SMS SMS decreasing by 12.3%. In terms of utilization of health services, the outpatient rate due to acute attack was lower in the intervention group after intervention than that before intervention (χ2=7.129, P=0.008), and the outpatient rate due to acute attack was lower in the subjects who received the forecast service through mobile phone SMS than that before intervention (χ2=4.675, P<0.001). In terms of medical expenses, there was no significant difference between control group and intervention group with different intervention methods before intervention (P>0.05). After intervention, the difference between the control group and the intervention group with different intervention methods was statistically significant (H=11.864, P<0.05). The results of multiple comparisons showed that compared with the control group, the average annual medical expenses of patients receiving mobile phone SMS and telephone forecasting services after intervention were lower than those of the control group, and the difference was statistically significant (P<0.05). ConclusionMeteorological risk forecasting service can reduce the acute onset of COPD, reduce the rate of consultation and medical expenses due to acute onset, and provide scientific basis for the basic COPD health management model.
7.Chinese Medicine Regulates Hepatocellular Carcinoma-related Signaling Pathways: A Review
Chun YU ; Fen GAO ; Lanlan ZHENG ; Cai GUO ; Yanfang HE ; Jiaojiao XIE ; Xuan ZHANG ; Yanhua MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):232-243
Hepatocellular carcinoma (HCC) is a common tumor in the digestive tract, the formation mechanism of which remains to be fully elucidated. Although surgery, radiation, chemotherapy, targeted therapy, and immunotherapy have achieved significant results in the treatment of HCC, these methods are accompanied by a considerable number of adverse reactions and complications. In recent years, Chinese medicine has shown remarkable efficacy in the treatment of HCC, and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine, which exerts therapeutic effects via multiple components and multiple targets. However, the pathogenesis of HCC is exceptionally complex and not fully understood, which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Hedgehog, Wnt/β-catenin, nuclear factor-κB (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and transforming growth factor-β (TGF-β)/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis, inhibiting cell proliferation and migration, and blocking the cell cycle via the above pathways. However, the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets, new perspectives, and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.
8.Effect of strict intraoperative blood glucose control on postoperative hepatic allograft dysfunction in patients undergoing liver transplantation
Lei CUI ; Yi DUAN ; Zhifeng GAO ; Jiaojiao GUO ; Zheng ZHANG ; Huan ZHANG
Chinese Journal of Anesthesiology 2024;44(5):548-552
Objective:To evaluate the effect of strict intraoperative blood glucose control on postoperative hepatic allograft dysfunction in patients undergoing liver transplantation.Methods:A total of 164 patients of both sexes, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, undergoing orthotopic liver transplantation, were divided into strict intraoperative blood glucose control group (group S, 6.0-7.8 mmol/L) and routine blood glucose control group (group C, 4.1-10.0 mmol/L) using a random number table method. From the completion of anesthesia induction to the end of operation, arterial blood glucose was measured every 1 h, and blood glucose management was carried out in combination with the goal-oriented blood glucose control process. The occurrence of postoperative hepatic allograft dysfunction, infection within 30 days after surgery, offline extubation time, duration of intensive care unit stay and total length of hospital stay were recorded. Results:Compared with group C, the incidence of postoperative liver dysfunction and infection within 30 days after operation were significantly decreased ( P<0.05), and no significant change was found in the offline extubation time, duration of intensive care unit stay and total length of hospital stay in group S ( P>0.05). Conclusions:Strict blood glucose control during liver transplantation can decrease the development of postoperative liver dysfunction in patients.
9.Chemical Components Distribution and Transcriptome Analysis of Different Tissues from Codonopsis pilosula
Jiaojiao JI ; Junli DAI ; Jiankuan LI ; Lingya CAO ; Xin XIONG ; Jianping GAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):117-125
ObjectiveThe transcriptome characteristics of different tissues of Codonopsis pilosula were analyzed to illustrate the genetic basis of the accumulation of active ingredients in the root of C. pilosula, and to provide theoretical basis for its high-quality production and cultivation. MethodDifferent tissues of C. pilosula at flowering stage were selected as experimental materials, and the contents of tangshenoside Ⅰ, lobetyolin and atractylenolide Ⅲ were detected by high performance liquid chromatography(HPLC). RNA-Seq was used to perform transcriptome sequencing of different tissues, and the differentially expressed genes were screened and analyzed by Gene Ontology(GO) and Kyoto Gene and Encyclopedia of Genes and Genomes(KEGG) enrichment analysis, in order to explore the characteristics of active compound distribution and the transcriptional profiles. ResultThe contents of polysaccharides and tangshenoside Ⅰ in the root of C. pilosula were significantly higher than those in other tissues. The transcriptional profiles of the root were significantly different from those of stem, leaf and flower. Cluster analysis, GO and KEGG enrichment analysis of differential gene expression showed that the differential expression genes were mainly enriched in flavonoid and phenylpropanoid biosynthesis, sucrose-starch metabolism, plant hormone signal transduction, plant-pathogen interaction, mitogen-activated protein kinase(MAPK) cascade signal transduction, Adenosine triphosphate(ATP)-binding cassette(ABC) transporter and other pathways. The expression of genes related to biosynthesis of phenylpropanoid compounds were significantly up-regulated in the roots and flowers, and ABC transporter proteins were mostly highly expressed in the flowers. The expression of key enzyme genes for polysaccharide synthesis, such as sucrose:sucrose 1-fructosyltransferase(1-SST) and fructan 1-exohydrolase(1-Feh), were significantly up-regulated in the roots, and a large number of stress-responsive genes closely related to the accumulation of secondary metabolites were significantly up-regulated in the roots. ConclusionThe active compound content and transcriptional profiles in C. pilosula roots were significantly different from those in stem, leaf, flower and other tissues, showing tissue specificity. Meanwhile, the genes related to stress response and biosynthesis of active compound, such as fructan and phenylpropanoid compounds, were up-regulated in roots of C. pilosula.
10.Ferroptosis in Treatment of Liver Fibrosis with Chinese Medicine: A Review
Lanlan ZHENG ; Cai GUO ; Yanfang HE ; Jiaojiao XIE ; Fen GAO ; Chun YU ; Yanhua MA
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):235-244
Hepatic fibrosis characterized by various chronic liver injuries can lead to abnormal activation of hepatic stellate cells, unbalanced production and degradation of extracellular matrix proteins, and excessive deposition that destroys the normal structure of the liver. The aggravated liver fibrosis can cause irreversible cirrhosis and hepatocellular carcinoma, becoming a great challenge to the global health. Ferroptosis is a new form of iron-dependent cell death discovered in recent years, which mainly involves abnormal iron metabolism, lipid peroxide accumulation, and weakening of the antioxidant defense system. A number of studies have reported that inducing ferroptosis in hepatic stellate cells or alleviating ferroptosis in the liver can ameliorate liver fibrosis and reduce liver injury. Chinese medicine widely applied in the treatment of chronic liver diseases has demonstrated good safety, wide therapeutic effects, and easy access compared with Western medicine. Therefore, The intervention of hepatic stellate cells or hepatic ferroptosis by Chinese medicine may be a new direction for the prevention and treatment of liver fibrosis in the future. This paper summarized the various regulatory mechanisms of ferroptosis and expounded how ferroptosis affected the progression of liver fibrosis, providing theoretical support for the prevention and treatment of liver fibrosis with Chinese medicine in the future.


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