1.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
ObjectiveTo explore the mechanism by which Sini San (SNS) inhibits ferroptosis, alleviates inflammation and myocardial injury, and improves myocardial infarction (MI). MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, its target sites were predicted using the SwissTargetPrediction Database, and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards, Online Mendelian Inheritance in Man (OMIM) database, DrugBank, Therapeutic Target Database (TTD), FerrDb database and literature review, respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction (PPI) network was constructed using the STRING database, and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in, and the biological functions were clustered by the MCODE plug-in. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group, the model group, the SNS group, and the trimetazidine (TMZ) group. The mice were subcutaneously injected with isoprenaline (ISO, 5 mg·kg-1·d-1) to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram (ECG), and the tissue morphology changes were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA) levels were detected by biochemical assay. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin (IL)-6 and 4-hydroxynonenal (4-HNE). Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 (p-STAT3) in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6, IL-18, solute carrier family 7 member 11 (SLC7A11), arachidonic acid 15-lipoxygenase (ALOX15), and glutathione peroxidase 4 (GPx4) in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained, and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation, and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 (P0.01), down-regulated the expression of ALOX15 mRNA (P0.01), up-regulated the level of serum GSH, and the expressions of SLC7A11 and GPx4 mRNA, reduced MDA and 4-HNE levels (P0.05, P0.01). Additionally, SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis, reduced the area of MI, alleviated inflammation and myocardial injury, lowered the levels of serum CK, CK-MB, LDH, IL-6, and the mRNA expression levels of IL-16 and IL-18 (P0.05), and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels, inhibit ferroptosis in cardiomyocytes, alleviate inflammation and myocardial injury, thereby improving MI.
2.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
ObjectiveTo explore the mechanism by which Sini San (SNS) inhibits ferroptosis, alleviates inflammation and myocardial injury, and improves myocardial infarction (MI). MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, its target sites were predicted using the SwissTargetPrediction Database, and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards, Online Mendelian Inheritance in Man (OMIM) database, DrugBank, Therapeutic Target Database (TTD), FerrDb database and literature review, respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction (PPI) network was constructed using the STRING database, and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in, and the biological functions were clustered by the MCODE plug-in. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group, the model group, the SNS group, and the trimetazidine (TMZ) group. The mice were subcutaneously injected with isoprenaline (ISO, 5 mg·kg-1·d-1) to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram (ECG), and the tissue morphology changes were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA) levels were detected by biochemical assay. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin (IL)-6 and 4-hydroxynonenal (4-HNE). Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 (p-STAT3) in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6, IL-18, solute carrier family 7 member 11 (SLC7A11), arachidonic acid 15-lipoxygenase (ALOX15), and glutathione peroxidase 4 (GPx4) in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained, and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation, and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 (P0.01), down-regulated the expression of ALOX15 mRNA (P0.01), up-regulated the level of serum GSH, and the expressions of SLC7A11 and GPx4 mRNA, reduced MDA and 4-HNE levels (P0.05, P0.01). Additionally, SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis, reduced the area of MI, alleviated inflammation and myocardial injury, lowered the levels of serum CK, CK-MB, LDH, IL-6, and the mRNA expression levels of IL-16 and IL-18 (P0.05), and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels, inhibit ferroptosis in cardiomyocytes, alleviate inflammation and myocardial injury, thereby improving MI.
3.Radionuclide Drug Conjugates:China's 15-Year Research and Development Process and Latest Policy Support
Dan LIU ; Xiuqi LI ; Shupeng LIU ; Xiaofei WU ; Mengyang YU ; Hongyun WANG
Medical Journal of Peking Union Medical College Hospital 2025;16(4):847-854
Radionuclide drug conjugates(RDC)represent the culmination of interdisciplinary integra-tion.By virtue of their precise targeting capability,high diagnostic sensitivity,and remarkable therapeutic effi-cacy in tumor diagnosis and treatment,RDC has emerged as promising theranostic agents with immense applica-tion potential.This article systematically reviews the progress in RDC development in China from 2009 to 2024,encompassing an overview of RDC,its structure and classification,trends in clinical research,advances in clinical trials,and national policy support.The aim is to provide valuable insights for researchers in related fields,thereby facilitating further development and application of RDC-based therapeutics.
4.A case of Sj?gren′s syndrome combined with myasthenia gravis with literature review
Xueliang LIU ; Dongyu CHEN ; Fang LI ; Shupeng WU ; Xue LI ; Cong LIU ; Jiatian ZHENG
Chinese Journal of Rheumatology 2025;29(8):681-686
Objective:To enhance the understanding of clinical doctors on the concurrence of Sj?gren′s syndrome (SS) and myasthenia gravis (MG), provide reference forclinical diagnosis and treatment.Methods:The medical record of SS、MG patient Taian Central hospital in october 2021 was reviewed and a retrospective analysis was conducted. Based on the key words, the main databases domestic and abroad from Jan 1973 to April 2024. The cases reported in the literature were searched out and merged with our case and analyzed by SPSS 27.0. The measurement data of normal distribution were expressed by mean standard deviation ± s, and the measurement data of abnormal distribution were expressed by M( Q1, Q3). Counting data were expressed as examples and percentages (%) . Results:Twenty-one patients with SS complicated with MG were reviewed. Among them, 19(90.5%) patients were female. The average age was (47.6 ± 3.1) years, and the median time from onset to diagnosis was 24 (11, 78) months. There were 11 patients (52.4%) with myasthenia gravis as the initial presentation. The main clinical manifestations of patients with myasthenia muscle fatigue (80.9%, 17/21), gravis include fatigue ptosis (71.4%, 15/21), diplopia, blurred vision (57.1%, 12/21), dysphagia (33.3%, 7/21), joint pain (33.3%, 7/21), odysarthria, and unclear speech (23.8%, 5/21), hair loss (14.3%, 3/21), and swelling of the excocrine glands(9.5%, 2/21). Eighteen patients (85.7%, 18/21) showed positive anti acetylcholine receptor antibodies. Sixteen patients (76.2%) were positive for ANA, and 14 patients (66.8%) were positive for anti SSA or (and) anti SSB antibodies. Four patients (19.0%) also had other autoimmune diseases (Hashimoto′s thyroiditis, rheumatoid arthritis, optic neuritis). In terms of treatment, cholinesterase inhibitors were the most common treatment measure, applied to 18 patients (85.7%), followed by glucocorticoid therapy, and applied to 14 patients (66.8%). In addition, 7 patients (33.3%) received immunosuppressive agents therapy, 5 patients (23.8%) underwent thymectomy, 2 patients (9.5%) received intravenous human immunoglobulin injection, and 1 patient (4.8%) underwent plasma exchange. All patients showed improvement after treatment.Conclusion:SS and MG are both autoimmune diseases, and their coexistence is rare. Clinicans should be aware of this rare association. Early diagnosis is crucial for the treatment and prognosis of patients,and requiresa comprehensive assessment of clinical symptoms, laboratory tests, and auto-antibody test results.
5.Radionuclide Drug Conjugates:China's 15-Year Research and Development Process and Latest Policy Support
Dan LIU ; Xiuqi LI ; Shupeng LIU ; Xiaofei WU ; Mengyang YU ; Hongyun WANG
Medical Journal of Peking Union Medical College Hospital 2025;16(4):847-854
Radionuclide drug conjugates(RDC)represent the culmination of interdisciplinary integra-tion.By virtue of their precise targeting capability,high diagnostic sensitivity,and remarkable therapeutic effi-cacy in tumor diagnosis and treatment,RDC has emerged as promising theranostic agents with immense applica-tion potential.This article systematically reviews the progress in RDC development in China from 2009 to 2024,encompassing an overview of RDC,its structure and classification,trends in clinical research,advances in clinical trials,and national policy support.The aim is to provide valuable insights for researchers in related fields,thereby facilitating further development and application of RDC-based therapeutics.
6.Research progress on the role of the gut microbiota and its metabolites in leukemia and related complication
Jie LIU ; Meiling ZHANG ; Shupeng CHEN ; Zhenhui WU ; Yingjian ZENG
Chinese Journal of Comparative Medicine 2025;35(5):87-94
The incidence of leukemia,a malignant cancer originating from the hematopoietic system,is increasing annually.Although traditional treatment method such as chemotherapy and hematopoietic stem cell transplantation have improved patient survival rates to some extent,serious side effects,drug tolerance,and high recurrence rates remain.In recent years,studies have shown that the gut microbiota and its metabolites play an important role in the occurrence,development,and complications of leukemia.Imbalance of the gut microbiota can lead to decreased immune function and an intensified inflammatory response,which is a key factor driving disease progression.Some metabolites,such as short-chain fatty acids,enhance immune function and improve patient prognosis through intestinal barrier repair,while others,such as hydrogen sulfide and bile acids,show potential anti-tumor effects exerted through regulation of tumor cell apoptosis and immune balance.Traditional Chinese medicine aimed at regulating the structure of the gut microbiota and its metabolites has shown great potential in alleviating the side effects of chemotherapy for leukemia.This review covers the role of the gut microbiota and its metabolites in the occurrence,development,and complications of leukemia,and explores treatment strategies for regulating the microbiota,including fecal microbiota transplantation,probiotics,and traditional Chinese medicine intervention.We anticipate that this review will serve as a reference for improving the treatment and prognosis of leukemia.
7.Research progress on the role of the gut microbiota and its metabolites in leukemia and related complication
Jie LIU ; Meiling ZHANG ; Shupeng CHEN ; Zhenhui WU ; Yingjian ZENG
Chinese Journal of Comparative Medicine 2025;35(5):87-94
The incidence of leukemia,a malignant cancer originating from the hematopoietic system,is increasing annually.Although traditional treatment method such as chemotherapy and hematopoietic stem cell transplantation have improved patient survival rates to some extent,serious side effects,drug tolerance,and high recurrence rates remain.In recent years,studies have shown that the gut microbiota and its metabolites play an important role in the occurrence,development,and complications of leukemia.Imbalance of the gut microbiota can lead to decreased immune function and an intensified inflammatory response,which is a key factor driving disease progression.Some metabolites,such as short-chain fatty acids,enhance immune function and improve patient prognosis through intestinal barrier repair,while others,such as hydrogen sulfide and bile acids,show potential anti-tumor effects exerted through regulation of tumor cell apoptosis and immune balance.Traditional Chinese medicine aimed at regulating the structure of the gut microbiota and its metabolites has shown great potential in alleviating the side effects of chemotherapy for leukemia.This review covers the role of the gut microbiota and its metabolites in the occurrence,development,and complications of leukemia,and explores treatment strategies for regulating the microbiota,including fecal microbiota transplantation,probiotics,and traditional Chinese medicine intervention.We anticipate that this review will serve as a reference for improving the treatment and prognosis of leukemia.
8.A case of Sj?gren′s syndrome combined with myasthenia gravis with literature review
Xueliang LIU ; Dongyu CHEN ; Fang LI ; Shupeng WU ; Xue LI ; Cong LIU ; Jiatian ZHENG
Chinese Journal of Rheumatology 2025;29(8):681-686
Objective:To enhance the understanding of clinical doctors on the concurrence of Sj?gren′s syndrome (SS) and myasthenia gravis (MG), provide reference forclinical diagnosis and treatment.Methods:The medical record of SS、MG patient Taian Central hospital in october 2021 was reviewed and a retrospective analysis was conducted. Based on the key words, the main databases domestic and abroad from Jan 1973 to April 2024. The cases reported in the literature were searched out and merged with our case and analyzed by SPSS 27.0. The measurement data of normal distribution were expressed by mean standard deviation ± s, and the measurement data of abnormal distribution were expressed by M( Q1, Q3). Counting data were expressed as examples and percentages (%) . Results:Twenty-one patients with SS complicated with MG were reviewed. Among them, 19(90.5%) patients were female. The average age was (47.6 ± 3.1) years, and the median time from onset to diagnosis was 24 (11, 78) months. There were 11 patients (52.4%) with myasthenia gravis as the initial presentation. The main clinical manifestations of patients with myasthenia muscle fatigue (80.9%, 17/21), gravis include fatigue ptosis (71.4%, 15/21), diplopia, blurred vision (57.1%, 12/21), dysphagia (33.3%, 7/21), joint pain (33.3%, 7/21), odysarthria, and unclear speech (23.8%, 5/21), hair loss (14.3%, 3/21), and swelling of the excocrine glands(9.5%, 2/21). Eighteen patients (85.7%, 18/21) showed positive anti acetylcholine receptor antibodies. Sixteen patients (76.2%) were positive for ANA, and 14 patients (66.8%) were positive for anti SSA or (and) anti SSB antibodies. Four patients (19.0%) also had other autoimmune diseases (Hashimoto′s thyroiditis, rheumatoid arthritis, optic neuritis). In terms of treatment, cholinesterase inhibitors were the most common treatment measure, applied to 18 patients (85.7%), followed by glucocorticoid therapy, and applied to 14 patients (66.8%). In addition, 7 patients (33.3%) received immunosuppressive agents therapy, 5 patients (23.8%) underwent thymectomy, 2 patients (9.5%) received intravenous human immunoglobulin injection, and 1 patient (4.8%) underwent plasma exchange. All patients showed improvement after treatment.Conclusion:SS and MG are both autoimmune diseases, and their coexistence is rare. Clinicans should be aware of this rare association. Early diagnosis is crucial for the treatment and prognosis of patients,and requiresa comprehensive assessment of clinical symptoms, laboratory tests, and auto-antibody test results.
9.Clinical Landscape of Therapeutic Cancer Vaccines: Challenges and Opportunities
Shupeng LIU ; Mengyang YU ; Xiaofei WU ; Hongyun WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1356-1363
To explore the status and characteristics of clinical trials of therapeutic cancer vaccines, and provide the overall trend of clinical translational research of therapeutic cancer vaccines. The ClinicalTrial registration platform was employed to retrieve relevant clinical trial information of therapeutic cancer vaccines from 2002 to 2023. The current clinical landscape of therapeutic cancer vaccines was analyzed from the perspectives of the number of registrations, types of vaccines, trial design, and geographical distribution. A total of 1563 clinical trials for therapeutic cancer vaccines were obtained from 2002 to 2023, with an average annual registration of approximately 70 trials. Among these, phase Ⅰ trials accounted for 976 (62.4%, 976/1563), phase Ⅱ trials for 474 (30.3%, 474/1563), phase Ⅲ trials for 68 (4.4%, 68/1563), and other types for 45 (2.9%, 45/1563). Clinical trials from phase Ⅰ to phase Ⅲ were conducted in multiple regions worldwide, with multicenter clinical trials totaling 482 (31.8%) and single-center clinical trials totaling 1036 (68.2%). The main types of vaccines were cell vector vaccines (38.7%, 588/1518) and protein/peptide vaccines (34.1%, 518/1518), with the primary research designs being single-arm studies (55.3%, 840/1518) and randomized controlled trials (27.8%, 422/1518). The top five indications for the vaccines were melanoma (16.5%, 251/1518), glioblastoma (8.9%, 135/1518), breast cancer (8.6%, 130/1518), prostate cancer (8.5%, 129/1518), and lung cancer (8.1%, 123/1518). The overall development of clinical trials for therapeutic cancer vaccines has been stable and primarily focused on exploratory trials. The main types of vaccines were cell vector vaccines, and the main research designs were single-arm studies and randomized controlled trials. The vaccines were commonly indicated for melanoma, glioblastoma, and breast cancer. Currently, there are significant challenges in the clinical translation in this field, which may be due to the complexity of the immune microenvironment, patient heterogeneity, and the challenges in vaccine design and preparation. With the application of high-throughput technologies such as proteomics, genomic sequencing, and bioinformatics, it is expected that barriers in the research of therapeutic cancer vaccines would be overcome, thus leading to a better clinical translation landscape.
10.Establishment of colorectal cancer organoid models and analysis of factors influencing their culture success rates
Na XUE ; Bing HAN ; Wenhan WU ; Yanxia LI ; Guoqiang XING ; Jie ZHENG ; Shupeng ZHANG ; Qingguo FENG ; Qing WANG ; Liyan GUO
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(5):577-582
Objective To investigate the application of organoid technology in colorectal cancer research and analyze the factors influencing the success rate of organoid cultivation. Methods A total of 24 samples of colorectal cancer patients treated at Tianjin Fifth Central Hospital and cultured organoids using specific culture media and Matrigel. The samples were collected within 30 minutes post-excision and stored at 4℃ to minimize contamination and protein degradation. During the cultivation process,the authors recorded instances of bacterial or fungal contamination and the organoid growth,and test for their histological structure and expression of tumor markers. Additionally,by analyzing clinical information from the patients who provided the samples,explore potential factors that may affect the success rate of culturing colorectal cancer organoids. Results A success rate of 70.8% (17/24) was achieved in the cultivation of organoid. The success rate of organoid culture was significantly different from that of tumor stage (all P<0.05),with significantly higher successful organoid cultivation rate for stage Ⅱ and stage Ⅲ tumor tissues than those for stageⅠand Ⅳ[83.3% (5/6),90.9% (10/11) vs. 33.4% (1/3),25.0% (1/4)]. Additionally,samples with a Ki-67 positive area proportion of 55%-70% exhibited the highest success rate (100%). Phenotypic experiments on the organoids indicated that their pathological histological structure and the expression of tumor markers were consistent with those of the primary tissues,suggesting that the organoids retained the histological characteristics of the primary lesions. Conclusions This study successfully established a colorectal cancer organoid model revealing the impact of tumor staging and the proportion of Ki-67 positive areas on the success rate of culture. The organoid model effectively retains the histological characteristics of the primary lesion,providing a powerful in vitro tool for the research and treatment of colorectal cancer.

Result Analysis
Print
Save
E-mail