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.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
4.Effect of preemptive analgesia with ibuprofen on postoperative pain after mandibular third molar extraction: a randomized controlled trial
Xuezhu WEI ; Kang GAO ; Jing ZHANG ; Bin ZHAO ; Zhiguang LIU ; Ruiqing WU ; Mingming OU ; Qi ZHANG ; Wei LI ; Qian CHENG ; Yilin XIE ; Tianyi ZHANG ; Yajie LI ; Hao WANG ; Zuomin WANG ; Wei ZHANG ; Jian ZHOU
Chinese Journal of Stomatology 2024;59(3):230-236
Objective:To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application.Methods:This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively.Results:All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] ( Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] ( Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] ( Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] ( Z=-2.81, P=0.005). Conclusions:A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.
5.Effect of preoperative oral ibuprofen on postoperative pain after dental implantation: a randomized controlled trial
Kang GAO ; Xuezhu WEI ; Bin ZHAO ; Zhiguang LIU ; Conglin DU ; Xin WANG ; Yao WANG ; Changying LIU ; Dezheng TANG ; Qi ZHANG ; Ruiqing WU ; Mingming OU ; Wei LI ; Qian CHENG ; Yilin XIE ; Pan MA ; Jun LI ; Hao WANG ; Zuomin WANG ; Su CHEN ; Wei ZHANG ; Jian ZHOU
Chinese Journal of Stomatology 2024;59(8):777-783
Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.
6.Cancer Death and Distribution Characteristics from 2013 to 2017 in Cixian, Hebei Province
Guohui SONG ; Zhiguang GAO ; Chao CHEN ; Yanwei GONG ; Tao SHANG
Cancer Research on Prevention and Treatment 2023;50(10):999-1003
Objective To investigate the cancer death and distribution characteristics of residents in Cixian County. Methods In accordance with the norms of cancer registration, cancer death data from 2013 to 2017 in Cixian were collected and analyzed, and the crude cancer death rate, age-standardized mortality rates by the Chinese standard population (ASMRC), age-standardized mortality rates by the global standard population (ASMRW). Results From January 1st, 2013, to December 31st, 2017, 6 490 cases of cancer death were recorded. The average annual crude mortality rate was 202.88/100 000, ASMRC was 186.49/100 000, and the ASMRW was 189.02/100 000. The top 10 male mortality cancers were esophageal cancer, stomach cancer, trachea, bronchus and lung cancer, liver cancer, rectal cancer, cerebral nervous system cancer, colon cancer, leukemia, pancreatic cancer, and bladder cancer in order. The top 10 female mortality cancers were esophageal cancer, trachea, bronchus and lung cancer, stomach cancer, liver cancer, breast cancer, cervical cancer, colon cancer, brain, nervous system cancer, rectal cancer, and ovarian cancer. The age of death increased considerably from the age of 40 years. It increased with the increase in age and reached the peak at the age of 85 years. Conclusion Upper gastrointestinal cancer and lung cancer were the main cancers that threatened the residents of Cixian County from 2013 to 2017. Screening and comprehensive prevention of high-risk groups are still the main targets of cancer prevention and control.
7.Open reduction and internal fixation assisted by computer virtual surgery in the treatment of complex proximal humeral fracture
Qinghui HAN ; Peng ZHANG ; Han WANG ; Zhiguang GAO ; Tao WANG
Chinese Journal of Trauma 2023;39(2):138-144
Objective:To investigate the effect of open reduction and internal fixation assisted by computer virtual surgery in the treatment of complex proximal humeral fracture.Methods:A retrospective case series study was performed on clinical data of 36 patients with complex proximal humeral fracture admitted to Dongfang Hospital Affiliated to Tongji University from January 2018 to June 2020. There were 13 males and 23 females, aged 22-86 years [(56.4±4.8)years]. They were all closed fractures. According to Neer classification, there were 20 patients with three-part fractures and 16 with four-part fractures. Precise pre-surgical designs made by using the digital orthopedic surgery planning system of the E-3D were applied to assist the implementation of precise fracture reduction and internal fixation with the locking plate. The fracture healing was observed. The effect of the real surgery assisted by the virtual surgical designs was assessed by comparing the humeral neck shaft angle and humeral head height measured at the virtual surgery and at day 1 after the real surgery. The humeral neck shaft angle, humeral head height, shoulder range of motion (abduction, external rotation and forward flexion), Constant shoulder function score and visual analogue score (VAS) were recorded at 1 day, 3 months and 12 months after the real surgery. The stability of the medial column was assessed at 1 day after the real surgery. The complications were recorded.Results:All patients were followed up for 12-38 months [(18.5±1.8)months]. The fracture showed bony union in all patients with the union time of 6.6-17.2 weeks [(10.2±1.0)weeks]. The humeral neck shaft angle and humeral head height showed no significant differences measured at the virtual surgery and at 1 day after the real surgery, and were also not significant different at 1 day, 3 months and 12 months after the real surgery (all P>0.05). At 3 months and 12 months after the real surgery, the shoulder abduction [(119.4±11.8)°, (155.3±13.7)°], external rotation [(37.6±6.3)°, (46.8±7.4)°], forward flexion [ (94.8±10.2)°, (126.9±1.6)°] and Constant function score [(66.8±8.4)points, (82.4±9.6)points] were all higher than those at 1 day after the real surgery [(53.8±4.5)°, (21.6±3.3)°, (44.6±7.8)°, (34.3±6.1)points], while the VAS [(4.1±0.5)points, (1.2±0.2)points] was lower than that at 1 day after the real surgery [(8.3±1.4)points] (all P<0.05). The medial column was stable in 34 patients and unstable in 2 at 1 day after the real surgery. Complications included screw cutting out in the articular surface in 1 patient and humeral head necrosis in 1. Conclusion:Treatment of complex proximal humeral fractures with open reduction and internal fixation assisted by computer virtual surgery is conducive to maintaining reduction effect, promoting shoulder joint function, relieving pain and reducing complications.
8.Application of regression discontinuity design in epidemiological research
Zhaoyan GUO ; Li LIU ; Fangfang YU ; Junyi WANG ; Yang GAO ; Zhiguang PING
Chinese Journal of Preventive Medicine 2021;55(9):1168-1172
Regression discontinuity design (RDD) is a rigorous quasi-experimental method. Based on the randomness of the distribution of samples around the critical value, the data on both sides are used for regression respectively, so as to avoid the interference of potential confounding factors and provide strong evidence for the inference of causal correlation. This study introduces the RDD and its research progress, and expounds its application in detail combined with cases, in order to provide reference for the application of RDD in epidemiological research.
9.Application of regression discontinuity design in epidemiological research
Zhaoyan GUO ; Li LIU ; Fangfang YU ; Junyi WANG ; Yang GAO ; Zhiguang PING
Chinese Journal of Preventive Medicine 2021;55(9):1168-1172
Regression discontinuity design (RDD) is a rigorous quasi-experimental method. Based on the randomness of the distribution of samples around the critical value, the data on both sides are used for regression respectively, so as to avoid the interference of potential confounding factors and provide strong evidence for the inference of causal correlation. This study introduces the RDD and its research progress, and expounds its application in detail combined with cases, in order to provide reference for the application of RDD in epidemiological research.
10.CT manifestations and prognosis of acute paraquat induced lung injury
Yi ZHAO ; Zhiguang TIAN ; Tie XU ; Fuhai GAO ; Yanyan GUO ; Guangjun WANG ; Yingge XU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(2):140-144
Objective:To investigate the CT features of lung injury induced by paraquat poisoning and its relationship with prognosis, and to provide reference for the judgment of the condition and prognosis of paraquat poisoning.Methods:146 cases of paraquat poisoning patients were treated in the Third People's Hospital of Xuzhou City from January 2013 to April 2016. The cases were divided into mild group, moderate-severe group and fulminant group according to the concentration of paraquat in urine. The clinical data and CT imaging findings were analyzed and reconstructed in three-dimensional reconstruction. The extent of the lesion was observed and the relationship between CT and prognosis was explored.Results:Paraquat lung injury has many manifestations on CT images, and it's performance can be intersecting at the same time. Early lesions lighter cases, late CT imaging lesions can be completely absorbed or residual fibrosis, the prognosis was good; the early lesion was pulmonary consolidation, pleural effusion cases, the late CT image was usually pleural thickening and bronchiectasis, the prognosis was relatively good; early lesions were large patches of ground glass opacity cases, finally, pulmonary fibrosis was common, the mortality rate of 56.57%. There were significant differences in the extent of lung injury between different groups ( P<0.001) , and the difference in mortality was statistically significant when the lung injury was different ( P<0.001) . Multivariate stepwise Logistic regression analysis showed that ground-glass opacity ( OR value=2.013) , interstitial lung fibrosis ( OR=3.779) and mediastinal emphysema ( OR=33.118) were risk factors for death of lung injury caused by paraquat poisoning ( P<0.05) . Conclusion:There were many manifestations on CT images of paraquat lung injury, and the manifestations of paraquat lung injury can be intersecting at the same time. The pulmonary manifestations and outcomes of different paraquat types were different. The CT manifestations of lung injury in paraquat poisoning were mainly exudative changes at early stage, and can be gradually absorbed or evolved into interstitial changes at later stage. The cumulative damage range can be used as a reference for evaluating the prognosis. Ground-glass opacity, interstitial pulmonary fibrosis and mediastinal emphysema are the risk factors for death of lung injury caused by paraquat poisoning.

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