1.Transcriptome sequencing-based expression profiling of oxidative stress-related genes and circRNAs in ricin toxin-induced macrophage pyroptosis
Nan LU ; Mingxin DONG ; Lei YU ; Chengbiao SUN ; Yan WANG ; Na XU ; Wensen LIU ; Shumin GE
Journal of Jilin University(Medicine Edition) 2025;51(4):1007-1018
Objective:To analyze and identify the expression profiles of oxidative stress-related genes and circular RNAs(circRNAs)in ricin toxin(RT)-induced pyroptosis of mouse mononuclear macrophages(RAW264.7)using transcriptome sequencing and bioinformatics technology,and to preliminarily analyze their potential functions.Methods:The macrophages(RAW264.7 cells)were treated with RT to establish a cell pyroptosis model and divided into control group,40 μg·L-1 RT group,and 80 ng/mL RT group.Transmission electron microscope(TEM)was used to observe the morphology of the RAW264.7 cells in various groups;Western blotting method was used to detect the expression levels of the pyroptosis pathway-related proteins in the cells in various groups;80 μg·L-1 RT was selected for subsequent experiments.Transcriptome sequencing(RNA-Seq)was performed to obtain the circRNA and mRNA expression profiles in the RAW264.7 cells in control group and RT-treated group,followed by bioinformatics analysis.Results:Compared with control group,the cells in 40 and 80 μg·L-1 RT groups underwent morphological changes;the cells in RT groups showed obvious pyroptosis-like morphological changes,characterized by significant swelling of dying cells and the appearance of characteristic large bubbles on the plasma membrane.Compared with control group,the expression level of gasdermin DN-terminal fragment(GSDMD-N)protein in 40 and 80 μg·L-1 RT groups was increased(P<0.05);compared with 40 μg·L-1 RT group,the expression level of GSDMD-N protein in the cells in 80 μg·L-1 RT group was increased(P<0.05);therefore,the subsequent experiments used the RT concentration of 80 μg·L-1.A total of 2930 differentially expressed messenger RNAs(mRNAs)and 24 differentially expressed circRNAs were identified.The constructed circRNA-microRNA(miRNA)-mRNA competing endogenous RNA(ceRNA)regulatory network consisted of 7 circRNAs,12 miRNAs and 13 mRNAs.Gene Ontology(GO)functional enrichment analysis showed that in biological process(BP),the functions regulated by differentially expressed genes mainly included immune response and oxidative stress response;in cellular component(CC),differentially expressed genes were mainly localized to the external side of plasma membrane and cell leading edge;in molecular function(MF),they were mainly involved in transporter transmembrane activity and hormone receptor binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that differentially expressed genes were mainly enriched in Toll-like receptor signaling pathway,Forkhead box O(FoxO)signaling pathway and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.In the protein-protein interaction(PPI)network,the top 10 hub genes with the highest connectivity were screened by CytoHubba,including matrix metalloproteinase 9(MMP9),superoxide dismutase 2(SOD2),and v-src sarcoma viral oncogene homolog(Src).Conclusion:The expression profiles of oxidative stress-related genes and circRNAs in RAW264.7 cells are altered after RT treatment.The screened differentially expressed circRNAs and mRNAs may serve as potential targets to regulate RT-induced pyroptosis in RAW264.7 cells through oxidative stress pathways.
2.The correlation of serum hypoxia-inducible factor-1α level with cerebral microbleeds and cognitive impairment
Qing LI ; Xiaowen ZHAO ; Jing REN ; Miao YU ; Hanfang CUI ; Fangyuan DING ; Hao LIU ; Qiong LI ; Fan WANG ; Qing LI ; Xiyan CHEN ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Journal of Capital Medical University 2025;46(2):216-227
Objective To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α)levels and cerebral microbleeds(CMBs)and cognitive impairment and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment.Methods A total of 104 patients with CSVD who attended the Department of Neurology,First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled.All enrolled patients were subjected to basic statistics,cranial nuclear magnetic resonance examination,cognitive function assessment,and serum HIF-1α test,and the number and location of CMBs were counted.Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed,and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated.Results There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups.Serum HIF-1α levels were significantly negatively correlated with overall cognitive function,visuospatial and executive function,attention,and delayed recall,and serum HIF-1α was positively correlated with the number of CMBs.HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD,and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD.Conclusion Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment,and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.
3.The correlation between serum sTREM2 levels and cognitive impairment in patients with cerebral small vessel disease
Hanfang CUI ; Fangyuan DING ; Zhixiu XU ; Qing LI ; Yifan ZHANG ; Sen ZHANG ; Mengke GAO ; Yuhui CHEN ; Xiaowen ZHAO ; Jialu ZHAO ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):976-982
Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.
4.The correlation between serum sTREM2 levels and cognitive impairment in patients with cerebral small vessel disease
Hanfang CUI ; Fangyuan DING ; Zhixiu XU ; Qing LI ; Yifan ZHANG ; Sen ZHANG ; Mengke GAO ; Yuhui CHEN ; Xiaowen ZHAO ; Jialu ZHAO ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):976-982
Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.
5.The correlation of serum hypoxia-inducible factor-1α level with cerebral microbleeds and cognitive impairment
Qing LI ; Xiaowen ZHAO ; Jing REN ; Miao YU ; Hanfang CUI ; Fangyuan DING ; Hao LIU ; Qiong LI ; Fan WANG ; Qing LI ; Xiyan CHEN ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Journal of Capital Medical University 2025;46(2):216-227
Objective To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α)levels and cerebral microbleeds(CMBs)and cognitive impairment and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment.Methods A total of 104 patients with CSVD who attended the Department of Neurology,First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled.All enrolled patients were subjected to basic statistics,cranial nuclear magnetic resonance examination,cognitive function assessment,and serum HIF-1α test,and the number and location of CMBs were counted.Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed,and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated.Results There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups.Serum HIF-1α levels were significantly negatively correlated with overall cognitive function,visuospatial and executive function,attention,and delayed recall,and serum HIF-1α was positively correlated with the number of CMBs.HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD,and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD.Conclusion Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment,and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.
6.Correlation between serum GDNF level and neuroimaging changes and cognitive impairment in patients with cerebral small vessel disease
Fangli YANG ; Hao LIU ; Fan WANG ; Qing LI ; Xiyan CHEN ; Ruiyan CAI ; Qingwu WU ; Jian ZHANG ; Sibei JI ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(9):809-815
Objective:To investigate the relationship between serum glial cell line-derived neurotrophic factor (GDNF) levels and neuroimaging changes and cognitive impairment in patients with cerebral small vascular disease (CSVD).Methods:135 patients with CSVD recruited from the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from September 2021 to July 2022 were assessed by cranial multimodal magnetic resonance imaging and Montreal cognitive function assessment (MoCA), and the basic data were analyzed at the same time.The serum GDNF concentration of all patients was detected by enzyme-linked immunosorbent assay (ELISA). According to the median GDNF concentration, the patients were divided into low GDNF group and high GDNF group. The baseline data, MoCA score and imaging markers of the two groups were compared by Mann-Whitney U test, chi-square test, logistic regression, Kruskal-Wallis H test and Jonckheere-Terpstra trend test, and the correlation between serum GDNF level and imaging markers and cognitive function of patients with CSVD was analyzed. Results:The median serum GDNF concentration of all CSVD patients was 16.66 pg/mL. Multivariate logistic regression analysis showed that low serum GDNF level was a risk factor for white matter hyperintensity and total image load in patients with CSVD. Serum GDNF level was a protective factor of cognitive impairment in patients with CSVD in multiple logistic regression analysis. The area under the curve of ROC curve analysis of cognitive impairment after CSVD predicted by serum GDNF level was 0.735, the sensitivity was 66.4%, and the specificity was 71.4%. The level of serum GDNF was positively related with visual space and executive function, attention and computational power, delayed recall and orientation( r=0.267, 0.187, 0.219, 0.215, all P<0.05). Conclusion:The serum GDNF level is related to white matter hyperintensities, total imaging load and cognitive impairment in patients with CSVD. Serum GDNF level may play a predictive role in CSVD and cognitive impairment.
7.Apatinib enhances the anti-tumor effect of cisplatin on gastric cancer by inhibiting HMGA2
ZHAN Fajie ; ZHU Haiyan ; LYU Yuxina ; SU Guohong ; LU Yimin ; LI Chengbiao
Chinese Journal of Cancer Biotherapy 2020;27(10):1131-1137
[Abstract] Objective: To investigate the effect of apatinib (APA) combined with cisplatin (DDP) on the proliferation, invasion and
migration capacity of gastric carcinoma (GC) cells and its molecular mechanism. Methods: Cancer and para-cancerous tissue samples
resected from 50 GC patients, who were surgically treated in Wuwei People's Hospital from January 2016 to June 2019, were
collected for this study; in addition, GC cell lines MGC803 and SGC7901 were also collected. qPCR was used to detect the HMGA2
expression in tissues and mRNA expressions of molecules related to cell proliferation, migration and invasion in GC cell lines.
MGC803 and SGC7901 cells were transfected with pcHMGA2 by liposome transfection technology. After treatment with DDP and
APA at different concentrations, the cells were divided into NC, pcHMGA2, pcHMGA2+DDP and pcHMGA2+DDP+APA groups.
Protein expression of HMGA2 in GC cells was detected by Western blotting, and proliferation, migration and invasion of the cells were
detected by MTT and Transwell assay, respectively. Results: The mRNA expression of HMGA2 in GC tissues was higher than that in
para-cancerous tissues (P<0.05), and the survival rate of GC patients in the high expression group was significantly reduced (P<0.01).
DDP significantly inhibited the proliferation, invasion and migration of MGC803 and SGC7901 cells (all P<0.01); the proliferation,
invasion and migration of MGC803 and SGC7901 cells in DDP+APA group significantly decreased (all P<0.01) as compared with
DDP group; APA significantly enhanced the inhibitory effect of DDP on HMGA2 expression in GC cells (P<0.01); APA enhanced
the anticancer activity of DDP against GC by down-regulating HMGA2 expression. Conclusion: APA promotes the anticancer
activity of DDP against GC, and its molecular mechanism is the promotion of the inhibitory effect of DDP on HMGA2 expression.
8.Investigation on the ability of general practitioners in Shenzhen to cope with the epidemic situation of COVID-19
Zhuo LI ; Zhiwei HUANG ; Chengbiao LIN ; Wenshi XIE ; Ye LU ; Yang LI ; Ying LIU
Chinese Journal of General Practitioners 2020;19(11):1009-1013
Objective:To investigate the work requirement and training needs of general practitioners in Shenzhen during the outbreak of coronal virus disease 2019 (COVID-19).Methods:From February 19 to February 29, 2020, the questionnaires of "Coping with COVID-19 epidemic of genereal practitioners in Shenzhen region" were distributed to 4 002 general practitioners in Shenzhen hospitals and communities through the Questionnaire Star software. The changes of job content, education parttern, and the perception of roles before and during the epidemic were surveyed; the different roles of doctors engaged in general medicine before and after 2008 in education and community work were compared; the needs for training in epidemic prevention related knowledge for general practitioners were investigated.Results:A total of 382 questionnaires were recovered, of which 361 were valid, and the effective rate was 94.5%. The 83.1% (300/361) of general practitioners believed that the number of patients during the epidemic was significantly reduced. The main work was to screen community residents in epidemic areas (68.9%, 249/361), telephone counseling (54.0%, 195/361), and screening and follow-up of close contacts (42.9%, 155/361); 98.9% (357/361) of community doctors participated in outpatient education. Experienced doctors (starting work before 2008) were more willing to undertake management work in the epidemic (χ 2=77.370, P<0.05) . General practitioners′ needs for training were psychological interventions for residents under quarantine (80.6%, 291/361), home protection knowledge in the community (74.2%, 268/361), and isolation measures of the family with suspected patients (67.3%, 243/361), wearing and taking off protective gowns (65.1%, 235/361), collecting pharyngeal swab specimens (57.3%, 207/361) and patient referral procedures (52.4%, 189/361). The 60.6% (219/316) of general practitioners preferred information from the government press conference, expert opinion or the intranet of the organization (such as the hospital management department). Conclusion:General practitioners in Shenzhen took important screening, public education and counseling works during the COVID-19 epidemic, meanwile the training in the psychological intervention, the prevention and control knowledge related to the epidemic should be strengthend to better cope with the epidemics.
9.Portable Epileptic Seizure Monitoring Intelligent System Based on Android System.
Zhenhu LIANG ; Shufeng WU ; Chunlin YANG ; Zhenzhou JIANG ; Tao YU ; Chengbiao LU ; Xiaoli LI
Journal of Biomedical Engineering 2016;33(1):31-37
The clinical electroencephalogram (EEG) monitoring systems based on personal computer system can not meet the requirements of portability and home usage. The epilepsy patients have to be monitored in hospital for an extended period of time, which imposes a heavy burden on hospitals. In the present study, we designed a portable 16-lead networked monitoring system based on the Android smart phone. The system uses some technologies including the active electrode, the WiFi wireless transmission, the multi-scale permutation entropy (MPE) algorithm, the back-propagation (BP) neural network algorithm, etc. Moreover, the software of Android mobile application can realize the processing and analysis of EEG data, the display of EEG waveform and the alarm of epileptic seizure. The system has been tested on the mobile phones with Android 2. 3 operating system or higher version and the results showed that this software ran accurately and steadily in the detection of epileptic seizure. In conclusion, this paper provides a portable and reliable solution for epileptic seizure monitoring in clinical and home applications.
Algorithms
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Cell Phone
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Electrocardiography
;
Electroencephalography
;
instrumentation
;
Entropy
;
Epilepsy
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diagnosis
;
Humans
;
Monitoring, Physiologic
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instrumentation
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Neural Networks (Computer)
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Software
10.The Effects of transcranial ultrasound stimulation on motor functioning and anti-oxidative capacity in mice with Parkinson's disease
Yong WANG ; Baixu REN ; Shufeng WU ; Qing ZHONG ; Xiaoli LI ; Chengbiao LU
Chinese Journal of Physical Medicine and Rehabilitation 2015;37(7):488-492
Objective To investigate the effects of transcranial ultrasound stimulation (TUS) on the motor functioning and anti-oxidative capacity of mice with Parkinson's disease (PD).Methods Thirty-two inbred C57BL male mice were randomized into a normal control group,a model group,a sham TUS group and a TUS group (n =8 for each group) according to a random number table.A PD model was induced in the mice of the model,sham TUS and TUS groups by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 20 mg/kg intraperitoneally,while those in the normal control group were given saline.Low intensity (1 W) focused ultrasound (LIFU) at a frequency of 0.5 MHz was then applied to stimulate the nigra region,except for the mice in the sham TUS group,which were treated with the same procedure but with no ultrasound output.A pole climbing test was carried out before,2 weeks and 5 weeks after the injection of the MPTP.After 5 weeks the animals were sacrificed and the whole brain malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) content were measured.Results No significant differences in in pole climbing scores were observed among the four groups before the MPTP injections.However,the average value decreased significantly to (4.30 ± 1.19),(4.40 ± 0.23) and (4.80 ± 0.23) for the model,sham TUS and TUS groups respectively 2 weeks after the injection.It then rose to (5.12 ±0.83) and (5.51 ± 1.21)for the first two groups 3 weeks later,but was still lower that before the injection.After 5 weeks the TUS group's average score was significantly higher than 3 weeks earlier and than that of the model group and the sham TUS group.Compared with the control group,the other groups' average scores were all lower 2 weeks after MPTP injection,and those of the model and the sham TUS groups remained so 5 weeks after the injection.Five weeks after the injection,the average MDA content of the model group (10.2 ± 1.1 nmol/ml) and the sham TUS group (9.4 ±1.3 nmol/ml) were significantly higher than the normal control group (4.5 ± 0.8 nmol/ml),as well as the TUS group (6.8 ± 0.9 nmol/ml).However,GSH-Px enzyme activity in the model group (100 ± 35.4 U/mgprot) and the sham US group (444 ± 24.9 U/mgprot) was significantly lower than that in the normal control group (1262.5 ± 53 U/mgprot),together with the TUS group (1047.3 ± 77.8 U/mgprot).Conclusion TUS can improve motor function in PD,at least in mice.This may be due to its anti-oxidative capacity.

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