1.Bioinformatics Reveals Mechanism of Schisandrin B in Inhibiting Ferroptosis to Ameliorate Methionine and Choline Deficiency-induced Fatty Liver Disease in Mice
Zhifeng ZHU ; Wenting LI ; Yongjun CAO ; Yuanyuan LIN ; Yifei LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):74-83
ObjectiveNonalcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem, and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the high-throughput experiment- and reference-guide database of traditional Chinese medicine (HERB). GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets, and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, molecular docking was performed between schisandrin B and core targets, and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency (MCD) diet for the modeling of NAFLD. Mice were randomized into normal, model, positive drug (essentiale), and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and those of total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH), and Fe2+ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin (HE) and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and 4-hydroxynonenal (4-HNE) in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels, respectively, of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2), glutathione peroxidase 4 (GPX4), transferrin, and ferritin heavy chain (FTH) in the liver tissue. ResultsA total of 2 370, 2 547, and 1 451 targets of schisandrin B, NAFLD, and ferroptosis were obtained, in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis (SLC7A11 and SLC3A2). Animal experiments showed that schizandrin B significantly decreased the liver index, lowered the levels of ALT, AST, TC, TG, IL-6, IL-1β, and TNF-α, alleviated hepatocyte ballooning and inflammatory cell infiltration, and reduced lipid accumulation in the liver of NAFLD mice. In addition, schisandrin B significantly lowered the levels of MDA, 4-HNE, and Fe2+, elevated the level of GSH, up-regulated the protein and mRNA levels of SLC7A11, SLC3A2, and GPX4, and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.
2.The diagnostic value of DWI combined with serum AFP, DCP, and GTP/ALT ratio in distinguishing benign and malignant liver tumors
Hui SHAN ; Deping CHEN ; Yongjun CAO ; Yanqing HE ; Chuan XIA
Journal of Chinese Physician 2024;26(3):402-407
Objective:To explore the differential diagnostic value of abdominal diffusion-weighted imaging (DWI) combined with serum alpha fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), and the ratio of γ-glutamyl transpeptidase to alanine transaminase (GTP/ALT) in the diagnosis of benign and malignant liver tumors.Methods:Ninety liver tumor patients admitted to the Chenzhou First People′s Hospital from February 2020 to May 2022 were selected, including 48 malignant tumors and 42 benign tumors, and were divided into malignant group and benign group. The imaging findings of routine magnetic resonance imaging (MRI) and DWI examination were analyzed for two groups of patients. We compared the apparent diffusion coefficient (ADC) values, serum AFP, DCP levels, and GTP/ALT between two groups of patients. The diagnostic value of DWI, individual and combined detection of various serological indicators for malignant tumors was analyzed using receiver operating characteristic (ROC) curves.Results:There were significant differences in MRI and DWI imaging manifestations between the malignant and benign groups of patients. The ADC values and ADC index of patients in the malignant group at different b values of 50, 400, and 800 s/mm 2 were lower than those in the benign group, and the differences were statistically significant (all P<0.05). The serum AFP, DCP, and GTP/ALT of patients in the malignant group were higher than those in the benign group, and the differences were statistically significant (all P<0.05). The ROC curve analysis results showed that the sensitivity and specificity of DWI combined with serum AFP, DCP, and GTP/ALT in diagnosing liver malignant tumors were higher than those of DWI alone and each serological indicator alone. Conclusions:The combination of DWI, serum AFP, DCP, and GTP/ALT has high sensitivity and specificity in diagnosing liver malignant tumors, and has certain clinical value in distinguishing between benign and malignant liver tumors.
3.Protective effect of luteolin on acute lung injury induced by extracorporeal circulation and its mechanism
Yunfei LING ; Tiange LI ; Rong CAO ; Yongjun QIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(08):1181-1187
Objective To investigate the protective effect of atomized inhalation of nano-luteolin preparation on acute lung injury caused by extracorporeal circulation, and to explore the anti-inflammatory mechanism of luteolin, so as to provide study basis for clinical application. Methods Thirty male SD rats aged 5-6 weeks and weighting 160-190 g, were randomly divided into a preoperative baseline (BL) group, arteriovenous partial diversion (ECC) group, luteolin atomization pretreatment for 1 h group, 2 h group, and 3 h group by random number method, with 6 rats in each group. In the BL group, lung tissue samples were collected directly without any treatment. The ECC group received mechanical ventilation, and the whole body was heparinized after the jugular arteriovenous intubation. The flow was transferred for 30 minutes, followed by observation for 60 minutes, then lung tissue samples were collected. Subjects in the 1 h, 2 h and 3 h groups were placed in a small animal atomizer 1 h, 2 h and 3 h before flow transfer respectively, and the subsequent operation was the same as that in the ECC group. The inflammatory level of lung tissue was detected to evaluate the degree of pathological injury of lung tissue. Western blotting (WB) was used to detect the contents of p65, IKKα, IKKβ and IKKγ in the cytoplasm of lung tissue samples of each group. Results Compared with the ECC group, the levels of IL-6 and TNF-α in lung tissues and the degree of pathological injury in the 1 h, 2 h and 3 h groups decreased, and the difference between the 3 h group and the ECC group was statistically different (P<0.05). WB results showed that compared with the ECC group, the levels of p65 in lung tissue of the 1 h, 2 h and 3 h groups decreased; the levels of IKKβ in the lung tissue increased in the 1 h, 2 h and 3 h groups, and the difference of the 3 h group was statistically different from the ECC group (P<0.05). Conclusion Luteolin has a protective effect on acute lung injury induced by ECC, and atomization 3 h in advance has the best protective effect on lung. The mechanism plays a protective role in ECC-induced acute lung injury, may be through inhibition of IKKβ phosphorylation, thereby inhibiting the classical NF-κB signaling pathway.
4.Neutrophil/lymphocyte ratio predicts discharge outcome in elderly patients with acute ischemic stroke receiving intravenous thrombolytic therapy
Yafang ZHU ; Shoujiang YOU ; Xia ZHANG ; Yan QIN ; Fengmei TIAN ; Liping TAN ; Yongjun CAO ; Dongqin CHEN
International Journal of Cerebrovascular Diseases 2023;31(12):889-894
Objective:To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) on the discharge outcome in elderly patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis (IVT).Methods:Elderly patients with AIS received IVT in the Department of Neurology, the Second Affiliated Hospital of Soochow University from August 2018 to August 2020 were retrospectively included. The modified Rankin Scale was used to evaluate discharge outcome, and the score >2 was defined as poor outcome. Symptomatic intracranial hemorrhage (sICH) was defined as any intracranial hemorrhage found on imaging examination accompanied by neurological deterioration, where the National Institutes of Health Stroke Scale (NIHSS) score increased by ≥4 from baseline or bleeding led to death. Multivariate logistic regression analysis was used to determine independent risk factors for sICH and poor discharge outcome. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of NLR for sICH and poor discharge outcome. Results:A total of 228 elderly patients with AIS receiving IVT were enrolled, including 118 males (51.8%), aged 73.64±8.16 years, with a baseline NIHSS score of 6.23±6.54. Ninety patients (39.5%) had poor outcome at discharge, and 16 (7.0%) developed sICH. Univariate analysis showed that the NLR in the poor outcome group was significantly higher than that in the good outcome group ( P<0.01). Multivariate logistic regression analysis showed that a higher NLR was an independent risk factor for poor discharge outcome (odds ratio [ OR] 1.245, 95% confidence interval [ CI] 1.044-1.484; P< 0.05) and sICH ( OR 1.124, 95% CI 1.010-1.251; P<0.05). ROC curve analysis showed that the area under the curve of NLR for predicting poor discharge outcome was 0.693 (95% CI 0.620-0.765; P<0.01). The optimal cutoff value was 4.345. Its corresponding sensitivity and specificity were 47.8% and 87.7%, respectively. The area under the curve of NLR for predicting sICH was 0.651 (95% CI 0.498-0.804; P<0.05). The optimal cutoff value was 3.515. Its corresponding sensitivity and specificity were 68.8% and 61.8%, respectively. Conclusions:A higher NLR is independently associated with sICH and poor discharge outcome in elderly patients with AIS receiving IVT, and have certain predictive value for sICH and poor discharge outcome.
5.Discussion on the construction system and management mode of county-level urinary iodine laboratory in Gansu Province
Yugui DOU ; Yanling WANG ; Wei SUN ; Jing ZHENG ; Yongjun LI ; Xiaoyan CHEN ; Xiaonan ZHU ; Yongqin CAO
Chinese Journal of Endemiology 2023;42(12):1021-1023
Iodine nutrition is very important to human health, especially for brain development, urinary iodinary is one of the basic indicators reflecting the nutritional status of iodine, and is an important basis for scientific evaluation of iodine nutrition. In order to provide support and assistance for improving the network syetem of iodine nutrition monitoring laboratories, we summarized and explored the construction process, quality control, and management methods of 85 county-level urinary iodine laboratories in Gansu Province from 2016 to 2018.
6.Nitrogen-doped carbon@TiO2 double-shelled hollow spheres as an electrochemical sensor for simultaneous determination of dopamine and paracetamol in human serum and saliva
Yang HUI ; Cao GONGXUN ; Huang YONGJUN ; Lin YE ; Zheng FENGYING ; Lin LUXIU ; Liu FENGJIAO ; Li SHUNXING
Journal of Pharmaceutical Analysis 2022;12(3):436-445
As the most commonly used antipyretic and analgesic drug,paracetamol(PA)coexists with neuro-transmitter dopamine(DA)in real biological samples.Their simultaneous determination is extremely important for human health,but they also interfere with each other.In order to improve the conductivity,adsorption affinity,sensitivity,and selectivity of TiO2-based electrochemical sensor,N-doped carbon@-TiO2 double-shelled hollow sphere(H-C/N@TiO2)is designed and synthesized by simple alcoholic and hydrothermal method,using polystyrene sphere(PS)as a template.Meanwhile,TiO2 hollow spheres(H-TiO2)or N-doped carbon hollow spheres(H-C/N)are also prepared by the same method.H-C/N@TiO2 has good conductivity,charge separation,and the highly enhanced and stable current responses for the detection of PA and DA.The detection limit and linear range are 50.0 nmol/L and 0.3-50 μmol/L for PA,40.0 nmol/L and 0.3-50 μmol/L for DA,respectively,which are better than those of carbon-based sen-sors.Moreover,this electrochemical sensor,with high selectivity,strong anti-interference,high reli-ability,and long time durability,can be used for the simultaneous detection of PA and DA in human blood serum and saliva.The high electrochemical performance of H-C/N@TiO2 is attributed to the multi-functional combination of different layers,because of good conductivity,absorption and electrons transfer ability from in-situ N-doped carbon and electrocatalytic activity from TiO2.
7.Coagulation and fibrinolysis parameters and mortality in patients with ischemic stroke: a 10-year follow-up study
Xuan ZHOU ; Le YIN ; Rui WANG ; Jiaping XU ; Xia ZHANG ; Chongke ZHONG ; Shoujiang YOU ; Yongjun CAO
International Journal of Cerebrovascular Diseases 2022;30(12):904-911
Objective:To investigate the long-term death of patients with ischemic stroke and its influencing factors.Methods:Based on the data of patients with ischemic stroke in the multi-center oral fibrinogen-lowering drug secondary prevention database, the follow-up patient information and the cause of death were registered through the epidemiological investigation method, and then compared with the baseline data of patients in the original database.Results:A total of 278 patients completed the follow-up, and 166 were in lumbrokinase group and 112 were in control group. There were 124 deaths (44.6%) within 10 years, of which 92 (74.2%) were vascular deaths. In the lumbrokinase group, 74 patients (44.6%) died of all causes and 55 (33.1%) died of vascular diseases; in the control group, 50 (44.6%) died of all causes and 37 (33.0%) died of vascular diseases. Cox proportional risk model analysis showed that lumbrokinase treatment had no significant effect on the 10-year survival rate of patients with ischemic stroke. The analysis of death influencing factors showed that the baseline international normalized ratio (INR) was significantly associated with the 10-year non-vascular death risk of patients (hazard ratio [ HR] 1.98, 95% confidence interval [ CI] 1.21-3.25; P=0.006). The greater the decrease of tissue plasminogen activator (tPA) within half a year, the lower the 10-year all-cause mortality risk ( HR 0.94, 95% CI 0.90-0.99; P=0.011); the greater the decrease in INR within one year , the lower the 10-year vascular death risk ( HR 0.41, 95% CI 0.17-0.96; P=0.040); the greater the decrease of D-dimer within one year , the higher the risk of the 10-year vascular death ( HR 1.37, 95% CI 1.02-1.83; P=0.034). The greater the decrease of INR in patients with ischemic stroke within one year, the higher the 10-year non-vascular death risk ( HR 2.15, 95% CI 1.29-3.59; P=0.004). Conclusions:The 10-year mortality rate of patients with ischemic stroke is higher, and about 3/4 are vascular deaths. The fibrinogen-lowering treatment in the acute stage has no significant effect on the 10-year all-cause mortality of patients with ischemic stroke. The greater the decrease of tPA in half a year, the lower the all-cause mortality; the greater the decrease of D-dimer level at baseline and within 1 year, the higher the 10-year vascular death; the greater the decrease of INR at baseline and within 1 year, the higher the 10-year non-vascular death risk.
8.Correction to: Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease.
Jianjun JIA ; Jun XU ; Jun LIU ; Yongjun WANG ; Yanjiang WANG ; Yunpeng CAO ; Qihao GUO ; Qiuming QU ; Cuibai WEI ; Wenshi WEI ; Junjian ZHANG ; Enyan YU
Neuroscience Bulletin 2022;38(3):337-338
9. Research progress on bone metabolism disorders associated with PCOS elucidated from endocrine hormones
Chen DU ; Yang CAO ; Chen DU ; Yongjun WANG ; Yan ZHANG ; He TIAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(3):328-333
Polycystic ovary syndrome (PCOS) is a common endocrine metabolic disease of women. Clinical studies have shown that PCOS patients are likely having abnormal bone metabolism, and with increased risk of osteoporosis. This review summarized the common pathological mechanisms for both PCOS and osteoporosis, and elucidated the research progress on PCOS-inducing bone metabolism disorders from emphasizing on the regulation of endocrine hormones including insulin, androgen, growth hormone, vitamin D, parathyroid hormone and calcitonin. It is expected that this review will shed new light on monitoring and intervention for bon health of PCOS patients.
10.Renal function and brain frailty in patients with mild stroke or transient ischemic attack
Guoli XU ; Zhiliang GUO ; Ruojun WANG ; Jiaping XU ; Yongjun CAO
International Journal of Cerebrovascular Diseases 2021;29(5):331-336
Objective:To investigate the correlation between peripheral blood renal function indexes and brain frailty imaging score in patients with mild ischemic stroke or transient ischemic attack (TIA).Methods:Patients with mild ischemic stroke or transient ischemic attack (TIA) admitted to the Department of Neurology, the Second Affiliated Hospital of Soochow University from March 2018 to August 2019 were enrolled retrospectively. General clinical data and peripheral blood renal function indexes, including urea, uric acid and estimated glomerular filtration rate (eGFR), were collected. eGFR <60 ml/(min·1.73 m 2) was used to reflect chronic kidney disease. According to the findings of MRI examination, the imaging score of cerebral frailty was performed. When there were white matter lesions, brain atrophy and lacunar infarction/lacuna, 1 point was given, and the total score was 3. Ordinal multi-class logistic regression analysis was used to evaluate the relationship between renal function indexes and brain frailty imaging score in patients with mild ischemic stroke or TIA. Binary logistic regression analysis was used to evaluate the relationship between renal function indexes and brain frailty imaging score >1. Results:A total of 204 patients with mild ischemic stroke or TIA were enrolled during the study. Their average age was 64.82 years old and 78 (38.2%) were females. There were 28 cases (13.73%), 70 cases (34.31%), 63 cases (30.88%) and 43 cases (21.08%) with brain frailty imaging scores of 0, 1, 2, and 3, respectively. One hundred and six patients (51.96%) were in the brain frailty imaging score >1 group and 98 (48.04%) were in the ≤1 group. Univariate analysis showed that there were significant differences in age, diabetes mellitus, eGFR, eGFR classification, homocysteine, intracranial vascular stenosis, stroke etiology classification and vascular distribution between the group with brain frailty imaging score >1 and those with brain frailty imaging score ≤1 (all P<0.05). Ordinal multi-class logistic regression analysis showed that urea (odds ratio [ OR] 0.67, 95% confidence interval [ CI] 0.51-0.89, P=0.005) and eGFR ( OR 0.98, 95% CI 0.96-0.99; P=0.004) were significantly and independently correlated with brain frailty imaging score. Binary logistic regression analysis showed that eGFR was significantly and independently correlated with brain frailty imaging score >1 ( OR 0.98, 95% CI 0.96-1.00; P=0.016). However, urea, uric acid and eGFR classification were not independently correlated with brain frailty imaging score or brain frailty imaging score >1. Conclusion:Blood urea and eGFR are correlated with the brain frailty imaging score in patients with mild ischemic stroke or TIA.

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