1.Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma Regulates Ferroptosis via Nrf2/SLC7A11/GPX4 Signaling Pathway to Alleviate Myocardial Remodeling in Rat Model of Myocardial Infarction
Xuesong CHEN ; Rongnan QIU ; Shenghao WANG ; Yan FENG ; Jutong XIE ; Yuwen YAN ; Tianlin YANG ; Changxu XIE ; Lei GAO ; Jianping SHEN ; Yuehong SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):54-62
ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group, ferroptosis inhibitor group (2 mg·kg-1), enalapril group (2.1 mg·kg-1), and low- and high-dose (4 g·kg-1 and 8 g·kg-1, respectively) Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma, with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment, echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin (HE) staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), transforming growth factor-β (TGF-β), and myosin heavy chain-β (MHC-β) were measured by enzyme-linked immunosorbent assay (ELISA). Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde (MDA) and glutathione (GSH) in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E2-related factor 2 (Nrf2) in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway. ResultsCompared with the sham group, the model group showed increased left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and serum levels of NT-proBNP, TGF-β, and MHC-β (P<0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01), disarrangement of myocardial cells, inflammatory cell infiltration, severe myocardial fibrosis, increased myocardial iron deposition, and irregular mitochondrial morphology with vacuolation. Furthermore, the modeling led to increased MDA (P<0.01), decreased GSH (P<0.01), diminished Nrf2 fluorescence intensity in the myocardial tissue, and downregulated expression levels of Nrf2, SLC7A11, and GPX4 (P<0.01). Compared with the model group, Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD, LVESD, and serum levels of NT-proBNP, TGF-β, and MHC-β (P<0.05, P<0.01), increased the LVEF and LVFS (P<0.05, P<0.01), alleviated pathological changes such as myocardial cell disarrangement, inflammatory cell infiltration, myocardial fibrosis, and iron deposition, lowered the level of MDA (P<0.05, P<0.01), raised the level of GSH (P<0.05, P<0.01), improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue, enhanced Nrf2 fluorescence intensity, and upregulated the expression levels of Nrf2, SLC7A11, and GPX4 (P<0.05, P<0.01) in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis, the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.
2.Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma Regulates Ferroptosis via Nrf2/SLC7A11/GPX4 Signaling Pathway to Alleviate Myocardial Remodeling in Rat Model of Myocardial Infarction
Xuesong CHEN ; Rongnan QIU ; Shenghao WANG ; Yan FENG ; Jutong XIE ; Yuwen YAN ; Tianlin YANG ; Changxu XIE ; Lei GAO ; Jianping SHEN ; Yuehong SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):54-62
ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group, ferroptosis inhibitor group (2 mg·kg-1), enalapril group (2.1 mg·kg-1), and low- and high-dose (4 g·kg-1 and 8 g·kg-1, respectively) Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma, with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment, echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin (HE) staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), transforming growth factor-β (TGF-β), and myosin heavy chain-β (MHC-β) were measured by enzyme-linked immunosorbent assay (ELISA). Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde (MDA) and glutathione (GSH) in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E2-related factor 2 (Nrf2) in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway. ResultsCompared with the sham group, the model group showed increased left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and serum levels of NT-proBNP, TGF-β, and MHC-β (P<0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01), disarrangement of myocardial cells, inflammatory cell infiltration, severe myocardial fibrosis, increased myocardial iron deposition, and irregular mitochondrial morphology with vacuolation. Furthermore, the modeling led to increased MDA (P<0.01), decreased GSH (P<0.01), diminished Nrf2 fluorescence intensity in the myocardial tissue, and downregulated expression levels of Nrf2, SLC7A11, and GPX4 (P<0.01). Compared with the model group, Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD, LVESD, and serum levels of NT-proBNP, TGF-β, and MHC-β (P<0.05, P<0.01), increased the LVEF and LVFS (P<0.05, P<0.01), alleviated pathological changes such as myocardial cell disarrangement, inflammatory cell infiltration, myocardial fibrosis, and iron deposition, lowered the level of MDA (P<0.05, P<0.01), raised the level of GSH (P<0.05, P<0.01), improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue, enhanced Nrf2 fluorescence intensity, and upregulated the expression levels of Nrf2, SLC7A11, and GPX4 (P<0.05, P<0.01) in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis, the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.
3.Research on the simplified version of multiple sleep latency test for diagnosing narcolepsy type 1
Zhe ZHU ; Yuanhang PAN ; Na YUAN ; Yuwen GAO ; Wenhao WEN ; Xinyu WEN ; Chenwei LI ; Yonghong LIU
Chinese Journal of Neurology 2025;58(10):1080-1086
Objective:To explore the feasibility of using a simplified multiple sleep latency test (MSLT) for the diagnosis of narcolepsy type 1.Methods:Data from 158 patients with narcolepsy type 1 and 58 patients with non-type 1 narcolepsy who underwent overnight video-polysomnography (V-PSG) and MSLT in the Sleep Center, Department of Neurology, Xijing Hospital, Air Force Military Medical University from March 2019 to April 2024 were retrospectively collected. By reducing the number of naps in the MSLT, the diagnostic consistency between the simplified MSLT and the standard 5-nap MSLT was evaluated using the receiver operating characteristic (ROC) curve. The DeLong test was used to compare whether there was a statistically significant difference between the simplified MSLT and the standard 5-nap MSLT. Cohen′s Kappa statistical analysis was performed to compare the diagnostic consistency between the simplified MSLT and the standard 5-nap MSLT.Results:The age of the 216 patients who were ultimately enrolled was 17 (13, 30) years, including 152 male patients (70.4%). The Cohen′s Kappa between the simplified 3-nap MSLT and the standard 5-nap MSLT was 0.875, which was 0.903 between the simplified 4-nap MSLT and the standard 5-nap MSLT (Bonferroni-corrected, both P0.001), indicating high and statistically significant agreement for both simplified protocols with the standard test. However, the DeLong test revealed that the area under the curve of the standard 5-nap MSLT (0.900, 95% CI 0.863-0.938) differed significantly from that of the simplified 3-nap MSLT (0.860, 95% CI 0.817-0.904; P0.05), whereas no significant difference was observed between the standard 5-nap MSLT and the simplified 4-nap MSLT (0.876, 95% CI 0.834-0.918; P0.05). Consequently, performing only the first 4 naps was sufficient for diagnosing narcolepsy type 1. Conclusion:The simplified 4-nap MSLT, specifically the first to fourth naps, may be used for the diagnosis of narcolepsy type 1.
4.Current situation analysis and quality evaluation of guidelines and consensus in ovarian stimulation for in vitro fertilization
Yuan GAO ; Zaiwei SONG ; Dan JIANG ; Rui YANG ; Yuwen HUANG ; Rong LI ; Rongsheng ZHAO
Chinese Journal of Reproduction and Contraception 2025;45(8):818-825
Objective:To systematically evaluate the current status and methodological quality of guideline and consensus in ovarian stimulation for in vitro fertilization (IVF), and to provide reference for the development of future guidelines and research. Methods:A systematic search was conducted in databases including PubMed, Embase, CNKI, Wanfang, Sinomed and relevant guideline websites from inceptions to October 2024. Data were extracted from the literature that met the inclusion criteria, and methodological quality was assessed using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) tool. Descriptive analysis was performed with results presented in visual data charts.Results:A total of 23 studies were included, with 8 guidelines and 15 consensus. Totally 21 (91.3%) studies focused on the selection of ovarian stimulation protocols, with the majority concentrating on protocols for patients undergoing IVF treatment for the first cycle, and 12 (52.2%) studies focused on the selection of gonadotropin starting dosage. In terms of methodology, the average standardized scores in the 6 assessment domains of the AGREE Ⅱ tool were as follows: scope and purpose (85.1%), stakeholder involvement (66.6%), rigour of development (36.5%), clarity of presentation (70.1%), applicability (36.4%), and editorial independence (46.2%).Conclusion:Current recommendations in ovarian stimulation for IVF exhibit inconsistencies, and the methodological quality varies, which partially hinders the translation of evidence into clinical practice. Future research should further focus on the selection of ovarian stimulation protocols and gonadotropin starting dosage, promoting the update and refinement of guidelines and consensus to guide the precise treatment of ovarian stimulation.
5.Current situation analysis and quality evaluation of guidelines and consensus in ovarian stimulation for in vitro fertilization
Yuan GAO ; Zaiwei SONG ; Dan JIANG ; Rui YANG ; Yuwen HUANG ; Rong LI ; Rongsheng ZHAO
Chinese Journal of Reproduction and Contraception 2025;45(8):818-825
Objective:To systematically evaluate the current status and methodological quality of guideline and consensus in ovarian stimulation for in vitro fertilization (IVF), and to provide reference for the development of future guidelines and research. Methods:A systematic search was conducted in databases including PubMed, Embase, CNKI, Wanfang, Sinomed and relevant guideline websites from inceptions to October 2024. Data were extracted from the literature that met the inclusion criteria, and methodological quality was assessed using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) tool. Descriptive analysis was performed with results presented in visual data charts.Results:A total of 23 studies were included, with 8 guidelines and 15 consensus. Totally 21 (91.3%) studies focused on the selection of ovarian stimulation protocols, with the majority concentrating on protocols for patients undergoing IVF treatment for the first cycle, and 12 (52.2%) studies focused on the selection of gonadotropin starting dosage. In terms of methodology, the average standardized scores in the 6 assessment domains of the AGREE Ⅱ tool were as follows: scope and purpose (85.1%), stakeholder involvement (66.6%), rigour of development (36.5%), clarity of presentation (70.1%), applicability (36.4%), and editorial independence (46.2%).Conclusion:Current recommendations in ovarian stimulation for IVF exhibit inconsistencies, and the methodological quality varies, which partially hinders the translation of evidence into clinical practice. Future research should further focus on the selection of ovarian stimulation protocols and gonadotropin starting dosage, promoting the update and refinement of guidelines and consensus to guide the precise treatment of ovarian stimulation.
6.Research on the simplified version of multiple sleep latency test for diagnosing narcolepsy type 1
Zhe ZHU ; Yuanhang PAN ; Na YUAN ; Yuwen GAO ; Wenhao WEN ; Xinyu WEN ; Chenwei LI ; Yonghong LIU
Chinese Journal of Neurology 2025;58(10):1080-1086
Objective:To explore the feasibility of using a simplified multiple sleep latency test (MSLT) for the diagnosis of narcolepsy type 1.Methods:Data from 158 patients with narcolepsy type 1 and 58 patients with non-type 1 narcolepsy who underwent overnight video-polysomnography (V-PSG) and MSLT in the Sleep Center, Department of Neurology, Xijing Hospital, Air Force Military Medical University from March 2019 to April 2024 were retrospectively collected. By reducing the number of naps in the MSLT, the diagnostic consistency between the simplified MSLT and the standard 5-nap MSLT was evaluated using the receiver operating characteristic (ROC) curve. The DeLong test was used to compare whether there was a statistically significant difference between the simplified MSLT and the standard 5-nap MSLT. Cohen′s Kappa statistical analysis was performed to compare the diagnostic consistency between the simplified MSLT and the standard 5-nap MSLT.Results:The age of the 216 patients who were ultimately enrolled was 17 (13, 30) years, including 152 male patients (70.4%). The Cohen′s Kappa between the simplified 3-nap MSLT and the standard 5-nap MSLT was 0.875, which was 0.903 between the simplified 4-nap MSLT and the standard 5-nap MSLT (Bonferroni-corrected, both P0.001), indicating high and statistically significant agreement for both simplified protocols with the standard test. However, the DeLong test revealed that the area under the curve of the standard 5-nap MSLT (0.900, 95% CI 0.863-0.938) differed significantly from that of the simplified 3-nap MSLT (0.860, 95% CI 0.817-0.904; P0.05), whereas no significant difference was observed between the standard 5-nap MSLT and the simplified 4-nap MSLT (0.876, 95% CI 0.834-0.918; P0.05). Consequently, performing only the first 4 naps was sufficient for diagnosing narcolepsy type 1. Conclusion:The simplified 4-nap MSLT, specifically the first to fourth naps, may be used for the diagnosis of narcolepsy type 1.
7.Transcriptional differential analysis of ocular surface ectoderm and surface ectoderm
Lu SUN ; Canwei ZHANG ; Yuwen SONG ; Jianxin LI ; Lian DUAN ; Yang GAO ; Yuemei XIE ; Luping WANG ; Guangfu DANG
International Eye Science 2024;24(5):677-685
AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.
8.Qualitative study on postoperative continuing health education needs of patients with degenerative scoliosis after surgery
Dongyue GAO ; Yaping DING ; Yun YOU ; Chaoyu YANG ; Ying WANG ; Yuwen XING
Chinese Journal of Modern Nursing 2024;30(18):2432-2436
Objective:To understand the current rehabilitation status and existing problems of patients with degenerative scoliosis after surgery, and analyze the needs of continuous health education for patients.Methods:A total of 15 patients with degenerative scoliosis undergoing surgical treatment in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from December 2021 to June 2022 were selected by the convenient sampling method. The semi-structured interview was used to understand the patient's feelings on the operation effect, experience on the postoperative life impact, thoughts on rehabilitation exercise, self-cognition of home status and future development planning. Based on the rooted theory, Colaizzi 7-step analysis was applied to extract the topic.Results:The four themes related to the continuous health education needs of patients with degenerative scoliosis after surgery were summarized, which were unacceptable movement limitation of lower back or lower extremity, blind area of continuous rehabilitation exercise, lack of knowledge of self-management of spinal disease after surgery and need for social and psychological support.Conclusions:Patients with degenerative scoliosis lack of postoperative rehabilitation knowledge and skills, and the need for health education is strong. Medical staff can meet the patients' transitional care needs by educating them to adapt to the current situation, providing personalized rehabilitation goals, guiding patients in managing risk factors that affect their own rehabilitation and improving social and family support systems, thereby promoting rapid recovery of patients.
9.Electro-clinical aspects of epilepsy with fixation-off sensitivity
Shuyi QU ; Xiaoli WANG ; Wenhao WEN ; Wenjuan ZHANG ; Yuwen GAO ; Xinyu WEN ; Yonghong LIU
Chinese Journal of Neurology 2024;57(12):1309-1316
Objective:To summarize the clinical and electrophysiological characteristics of epilepsy patients with fixation-off sensitivity (FOS).Methods:Using "fixation-off sensitivity" and "epilepsy" as search terms, data were retrieved from the Electroencephalogram Monitoring Center Database of Xijing Hospital, Air Force Military Medical University. Information was collected on epilepsy patients with FOS who were seen at the Xijing Hospital Electroencephalogram Monitoring Center from March 2019 to May 2023. A retrospective analysis of video electroencephalograms and clinical information was conducted, along with follow-up. Single factor analysis and multi-factor Logistic regression analysis were used to analyze the risk factors affecting the prognosis of the patients.Results:A total of 78 patients met the inclusion criteria, including 43 females and 35 males; the age at first epilepsy onset was 12.00 (8.00, 15.25) years. Among these 78 patients, 46 were diagnosed with genetic generalized epilepsy, 11 with self-limited focal epilepy, 9 with familial cortical myoclonic tremor with epilepsy, 7 with developmental and epileptic encephalopathy, 3 with symptomatic epilepsy, and 2 with progressive myoclonic epilepsy. The fixation-off induction trial most commonly triggered seizures in epilepsy with eyelid myoclonia (EEM) patients, with eyelid myoclonia being the most common type of seizure. Twenty-five epilepsy patients with FOS showed a positive photoparoxysmal response, of whom 6 experienced photo-convulsive response. Sixty-eight patients completed follow-up with comprehensive clinical data. At the last follow-up, 45 patients had been free from tonic-clonic seizures for at least one year. A history of febrile seizures ( OR=20.559, 95% CI 2.179-193.997, P=0.008) and cognitive decline ( OR=3.752, 95% CI 1.118-12.588, P=0.032) were identified as risk factors for poor prognosis in epilepsy patients with FOS. The age of first epilepsy onset, the number of anti-seizure medications, and the intermittent photo stimulation trial results had no correlation with prognosis. Conclusions:FOS is more common in female epilepsy patients and can be observed in both generalized and focal epilepsy syndromes. EEM patients are prone to seizures during fixation-off induction trial, and the most common type of seizures is eyelid myoclonus seizure. Patients with epilepsy with FOS who have a history of febrile seizures and cognitive impairment tend to have poor prognosis.
10.Research progress in epilepsy with eyelid myoclonia
Chenwei LI ; Yuwen GAO ; Xinyu WEN ; Wenhao WEN ; Yonghong LIU
Chinese Journal of Neurology 2024;57(12):1371-1376
Epilepsy with eyelid myoclonia (EEM), also known as Jeavons syndrome, is a type of genetic generalized epilepsy officially recognized by the International League Against Epilepsy. The clinical characteristics of EEM include eyelid myoclonia, eye closure sensitivity, and photosensitivity, typically manifesting in childhood with a higher prevalence in female patients. The prognosis of EEM is poor, and seizures are difficult to fully control even with standardized drug treatment. The electroencephalogram of EEM often shows fast interictal multiple spike-wave complexes, which can be induced by eye closure or photic stimulation. Functional magnetic resonance imaging and other studies have found that EEM is associated with brain network abnormalities, particularly the key role of the central medial thalamic nucleus in the regulation of cortical excitability. Genetic research has found that EEM may be related to variations in genes such as CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1.

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