1.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
2.Butyrate acts as a G-protein-coupled receptor ligand that prevents high glucose-induced amyloidogenesis in N2a cells through the protein kinase B/glycogen synthase kinase-3β pathway.
Yujie XU ; Shufang SHAN ; Xiaoyu WANG ; Lingli LI ; Liang MA ; Jingyuan XIONG ; Ping FU ; Guo CHENG
Chinese Medical Journal 2023;136(19):2368-2370
3.Associations between abnormal electroencephalogram microstates and childhood emotional abuse in adolescent depression
Jinhui HU ; Dongdong ZHOU ; Lin ZHAO ; Lingli MA ; Xinyu PENG ; Xiaoqing HE ; Ran CHEN ; Wanjun CHEN ; Zhenghao JIANG ; Li KUANG ; Wo WANG
Journal of Central South University(Medical Sciences) 2023;48(11):1678-1685
Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P<0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P<0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P<0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.
4.Association of serum NLR and SII with postmenopausal osteoporotic vertebral compression fractures and their predictive value for short-term prognosis
Zimeng LI ; Haochuan LIU ; Lingli MA ; Yulong LIU
Chinese Journal of Endocrine Surgery 2023;17(6):744-747
Objective:To explore the correlation between serum NLR and SII levels and postmenopausal osteoporotic vertebral compression fracture (OVCF) and to analyze the short-term prognostic value.Methods:A total of 132 patients with postmenopausal OVCF admitted to our hospital from Dec. 2018 to Dec. 2021 were selected as the study group, and 98 patients with postmenopausal osteoporosis but did not suffer from OVCF were selected as the control group. According to the recurrence of postmenopausal OVCF fractures, the ROC curves of NLR and SII were plotted, and their prognostic value for postmenopausal osteoporosis OVCF was analyzed.Results:NLR level was 2.96±0.41 and STI level was 39.41±23.45 in the control group. The level of NLR was 3.42±0.32 and SII was 431.77±31.14 in the research group ( P<0.05) . Multivariate Logistic regression analysis showed that lumbar bone density ( OR=0.030, 95%CI: 0.001-0.832, P=0.042) , NLR level ( OR=29.43, 95%CI: 9.840-103.6, P=0.001) and SII level ( OR=1.048, 95%CI: 1.034-1.066, P=0.001) were all risk factors affecting postmenopausal OVCF. NLR (3.77±0.22) and SII (441.32±29.68) in the recurrent fracture group were higher than NLR (3.27±0.22) and SII (426.87±30.57) in the non-recurrent fracture group, and the differences were statistically significant (all P<0.05) , multivariate Logistic regression analysis showed lumbar spine bone density ( OR=8.56×10 4, 95% CI: 3.884-2.992×10 10, P=0.045) , NLR level ( OR=1.243×10 -8, 95% CI: 2.911×10 -13-1.072×10 -5, P=0.001) and SII level ( OR=0.938, 95% CI: 0.885-0.976, P=0.008) were all influencing factors affecting the postoperative treatment effect of postmenopausal OVCF, and ROC results showed that both NLR (AUC=0.86, 95% CI: 0.77-0.94, P<0.001) and SII (AUC=0.76, 95% CI: 0.67-0.85, P<0.001) had good prognostic value for postmenopausal OVCF. Conclusion:NLR and SII are risk factors for OVCF in postmenopausal osteoporosis patients, and have good short-term prognostic value.
5.Research progress of risk prediction model for pulmonary infection in patients with cerebral hemorrhage
Juan YANG ; Yonghua WANG ; Lingli JIANG ; Yuan MA ; Aihua WANG ; Juan CHEN
Journal of Clinical Medicine in Practice 2023;27(24):144-148
Cerebral hemorrhage has a high incidence and numerous complications.Pulmonary in-fection is one of the serious complications of cerebral hemorrhage.Domestic and foreign researchers have developed pulmonary infection prediction models for patients with cerebral hemorrhage,which can provide references for clinical medical staff to identify high-risk groups in the early stage and formulate intervention strategies as soon as possible.This article summarized the risk factors of pulmonary infec-tion,the overview of risk prediction models,the current research status of pulmonary infection predic-tion models,and the significance of prediction,aiming to provide references for the evaluation and pre-vention of pulmonary infection in patients with cerebral hemorrhage.
6.Research progress of risk prediction model for pulmonary infection in patients with cerebral hemorrhage
Juan YANG ; Yonghua WANG ; Lingli JIANG ; Yuan MA ; Aihua WANG ; Juan CHEN
Journal of Clinical Medicine in Practice 2023;27(24):144-148
Cerebral hemorrhage has a high incidence and numerous complications.Pulmonary in-fection is one of the serious complications of cerebral hemorrhage.Domestic and foreign researchers have developed pulmonary infection prediction models for patients with cerebral hemorrhage,which can provide references for clinical medical staff to identify high-risk groups in the early stage and formulate intervention strategies as soon as possible.This article summarized the risk factors of pulmonary infec-tion,the overview of risk prediction models,the current research status of pulmonary infection predic-tion models,and the significance of prediction,aiming to provide references for the evaluation and pre-vention of pulmonary infection in patients with cerebral hemorrhage.
7.Ionizing radiation promotes epithelial-mesenchymal transition of cervical cancer cell line Siha through increasing the secretion of exosomes
Lingli LIAO ; Fan YANG ; Yuwei MA ; Luyao WANG ; Zhen QU ; Xiaojing WANG ; Hao JIANG ; Yongchun ZHOU
Chinese Journal of Radiological Medicine and Protection 2022;42(12):922-927
Objective:To observe the occurrence of epithelial-mesenchymal transition (EMT) in cervical cancer cell line Siha irradiated by X-rays with clinical conventional fraction radiotherapy model and investigate the role of exosomes in this process.Methods:Siha cells were irradiated by 6 MV-X rays with 50 Gy in 25 fractions. EMT was evaluated by cell morphology, EMT biomarkers and cell migration and invasion ability. Exosomes released from cells were detected by transmission electron microscopy and nanoparticle tracking analysis (NTA), and its function in EMT was explored by using an exosome inhibitor GW4869 (10 μmol/L).Results:After irradiation, EMT phenomenon was induced in the survived Siha cells, including the incidence of mesenchymal phenotype, upregulation of epithelial marker E-cadherin ( t=9.66, P<0.05), downregulation of mesenchymal marker N-cadherin ( t=41.61, P<0.05), and increase of cell migration and invasion abilities ( t=6.11, 13.22; P<0.05). Meanwhile, the secretion of exosomes was also increased after irradiation ( t=7.51, P<0.05). When the cells were pre-treated with GW4869, radiation-induced exosome secretion was reduced ( t=7.28, P<0.05), so that radiation-induced EMT was reversed. Conclusions:Ionizing radiation with clinical conventional fraction radiotherapy model promotes EMT of cervical cancer cells through increasing the secretion of exosomes.
8.Establishment of a TreeNet algorithm-based model for early prediction of essential hypertension
Xiaohong YU ; Yanmei QIAN ; Chenjie ZHOU ; Yue MA ; Yanchao TANG ; Lingli ZOU
Journal of Preventive Medicine 2022;34(9):923-927
Objective:
To create a model for early prediction of essential hypertension (EH) based on the TreeNet algorithm, so as to provide a tool for early monitoring of EH.
Methods:
The health examination data were collected from individuals receiving health examinations in Hangzhou Haiqin Health Examination Center or Shanghai Yibao Health Management Co., Ltd from 2014 to 2016, and a predictive model for EH was created based on the TreeNet algorithm. The effectiveness of the model for early prediction of EH was evaluated using root mean square error (RMSE), mean absolute deviation (MAD), coefficient of determination (R2) and receiver operating characteristic (ROC) curve.
Results:
A total of 12 variables were included in the model, and the highest contributing variable was body mass index (BMI), followed by BMI difference, two-year BMI difference, two-year triglyceride (TG) difference, two-year total cholesterol (TC) difference, high-density lipoprotein cholesterol (HDL-C) in 2014, TG in 2014, low-density lipoprotein cholesterol (LDL-C) in 2014, body weight in 2015, fasting blood glucose in 2015, TG in 2015, urea nitrogen difference and platelet in 2015. The highest predictive accuracy was 100.00%, and the lowest was 56.89%. The risk of EH significantly increased among individuals with BMI in 2015 of >25 kg/m2, two-year BMI difference of >0.5 kg/m2, two-year TG difference ranging from 1.3 to 3.3 mmol/L, TC in 2015 of 2.0 to 2.4 mmol/L and HDL-C in 2014 of <0.52 mmol/L. The model presented RMSE of 0.082, MAD of 0.064, R2 of 0.811, area under the ROC curve of 0.788 (95%CI: 0.741-0.815), sensitivity of 69.05% and specificity of 66.21% for prediction of EH
Conclusion
The TreeNet algorithm-based model is effective for early monitoring of high-risk individuals for EH.
9.Changes of electroencephalogram of patients with drug resistant epilepsy after vagus nerve stimulation
Shihua DANG ; Lingli JIANG ; Haifeng SHU ; Tao YANG ; Zhi ZHANG ; Zhichuang QU ; Sixun YU ; Xin CHEN ; Yuan MA ; Yufang ZHAO ; Hongmei WANG
Chinese Journal of Neuromedicine 2022;21(9):912-915
Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.
10.Changes of electroencephalogram of patients with drug resistant epilepsy after vagus nerve stimulation
Shihua DANG ; Lingli JIANG ; Haifeng SHU ; Tao YANG ; Zhi ZHANG ; Zhichuang QU ; Sixun YU ; Xin CHEN ; Yuan MA ; Yufang ZHAO ; Hongmei WANG
Chinese Journal of Neuromedicine 2022;21(9):912-915
Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.


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