1.Functional effects of microRNA-211-5p-targeted inhibition of erythropoietin hepatocyte kinase receptor and ligand B2 signaling pathway on spinal cord nerve injury
Mingwu LI ; Lihui QIAN ; Farui SUN ; Jun DUAN ; Liang LIU
Chinese Journal of Postgraduates of Medicine 2024;47(3):212-221
Objective:To detect the expression of microRNA (miR)-211-5p, erythropoietin hepatocyte kinase receptor B2 (EphB2) and erythropoietin hepatocyte kinase ligand B2 (ephrin B2) in spinal cord tissues as well as nerve cells after spinal cord injury (SCI), and to explore their mechanisms and effects on neurological recovery in SCI rats.Methods:The study was conducted from May 2020 to June 2021 using Sprague Dawley (SD) rats and PC12 cells. SD rats were divided into sham-operated group and SCI group of 30 rats each, and Basso-Beattie-Bresnahan (BBB) score were performed at different postoperative time points (1, 3, 7, 14, 21 and 28 d), and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA was measured by quantitative real-time polymerase chain reaction (qPCR); the SCI rats were divided into recombinant lentiviral vector LV-miR-211-5p group (group A), empty lentiviral vector LV-eGFP (group B) and saline group (group C), with 15 rats in each group, respectively. The recombinant lentiviral vector, empty lentiviral vector and saline were injected on the cephalic and caudal sides of the spinal cord injury, and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA in the spinal cord tissue was measured at 1, 7 and 14 d after surgery. In addition, a PC12 injury cell line model was established with 150 μmol/L hydrogen peroxide (H 2O 2), and the apoptosis rate and apoptosis-related proteins and contents of different cell lines were detected by flow cytometry and Western blot, respectively. MiR-211-5p was verified to target EphB2 by dual luciferase reporter gene. Results:The results of the animal experiments showed that at different postoperative time points, the miR-211-5p levels in the SCI group were lower than those in the SHAM group: 0.70 ± 0.03 vs. 1.00 ± 0.10, 0.60 ± 0.04 vs. 1.00 ± 0.05, 0.45 ± 0.10 vs. 1.00 ± 0.12, 0.30 ± 0.06 vs. 1.00 ± 0.15, 0.20 ± 0.05 vs. 1.00 ± 0.13, 0.10 ± 0.02 vs. 1.00 ± 0.07. In contrast, levels of Eph/ephrin B2 were higher in the SCI group compared to the SHAM group: 1.10 ± 0.05 vs. 1.00 ± 0.01, 1.80 ± 0.01 vs. 1.00 ± 0.08, 2.30 ± 0.01 vs. 1.00 ± 0.10, 2.60 ± 0.01 vs. 1.00 ± 0.05, 2.80 ± 0.01 vs. 1.00 ± 0.06, 3.00 ± 0.01 vs. 1.00 ± 0.07 and 1.20 ± 0.05 vs. 1.00 ± 0.02, 1.60 ± 0.01 vs. 1.00 ± 0.03, 2.10 ± 0.10 vs. 1.00 ± 0.01, 2.40 ± 0.11 vs. 1.00 ± 0.09, 2.70 ± 0.13 vs. 1.00 ± 0.05, 2.90 ± 0.12 vs. 1.00 ± 0.03 ( P<0.05). At 14 d after surgery, Group A exhibited higher BBB scores than Groups B and C: (14.0 ± 1.1) points vs. (8.0 ± 1.1) and (8.2 ± 1.2) points, while miR-211-5p levels were higher than those in Groups B and C: 1.90 ± 0.10 vs. 0.40 ± 0.01 and 0.50 ± 0.02, and Eph/ephrin B2 levels were lower than those in Groups B and C: 0.70 ± 0.10 vs. 1.80 ± 0.04 and 1.90 ± 0.06, 0.60 ± 0.03 vs. 2.00 ± 0.04 and 2.10 ± 0.05 ( P<0.05). Immunofluorescence staining showed that the levels of GAP-43 and synaptophysin in group A were higher than those in groups B and C at 14 d after surgery ( P<0.05). Cellular assays showed that overexpression of miR-211-5p inhibited the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Knockdown of miR-211-5p increased the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Dual luciferase reporter gene assay confirmed that EphB2 was a target gene of miR-211-5p and overexpression of EphB2 antagonized the inhibitory apoptosis effect of miR-211-5p on H 2O 2-induced PC12 cells. Conclusions:This study showed that miR-211-5p could promote neurological repair in SCI by inhibiting the expression of Eph/ephrin B2 signaling pathway, suggesting that using miR-211-5p as a target to inhibit Eph/ephrin B2 signaling pathway may have a protective effect on SCI.
2.Screening of serum exosomal miRNAs as diagnostic biomarkers in Alzheimer's disease
Xian DUAN ; Qing ZHENG ; Lihui LIANG ; Lin ZHOU
Journal of Army Medical University 2024;46(15):1803-1810
Objective To screen differentially expressed miRNAs(DEMs)by comparing the expression of miRNAs in serum exosomes between Alzheimer's disease(AD)patients and healthy controls.Methods A total of 71 AD patients admitted to Department of Geriatric Neurology of Xiangya Hospital from March 2017 to August 2018 and another 71 healthy individuals who taking physical examination in the hospital during same period were recruited and assigned into AD and HC groups,respectively.Four AD patients and four healthy subjects were selected for high-throughput second-generation sequencing of exosome miRNAs.The results were analyzed to obtain the DEMs between them,and the top 4 DEMs were finally selected.Then real-time quantitative real-time PCR was applied for all the subjects to detect the expression of the 4 DEMs.Results High-throughput second-generation sequencing detected 775 miRNAs,and 44 DEMs were found with statistical difference between the 2 groups(P<0.05).Compared with the HC group,34 miRNAs were up-regulated and 10 were down-regulated in the AD group.The top 4 DEMs were miRNA-148a-3p,miRNA-16-5p,miRNA-19b-3p and miRNA-483-5p.MiRNA-148a-3p was significantly up-regulated in the AD group than the HC group(P<0.01),but there were no significant differences in the expression level in the other 3 DEMs between the 2 groups.ROC curve analysis showed that the area under the curve of miRNA-148a-3p was 0.7113(95%CI:0.622~0.801),with a sensitivity of 71.6%and a specificity of 69.7%.Conclusion Serum exosome miRNA-148a-3p can be used as a biomarker for the diagnosis of AD.
3.Compensatory effects of exercise on abnormal brain activation in sleep disorders:an activation likelihood estimation meta-analysis
Wanting LI ; Lihui DUAN ; Jiawen WU
Journal of Clinical Neurology 2024;37(3):166-173
Objective To explore the compensatory effect of exercise on brain activation abnormalities caused by sleep disorders.Methods Brain imaging meta-analysis was conducted using activation likelihood estimation(ALE)to investigate brain activation abnormalities caused by sleep disorders and changes in brain activation related to exercise.Results A total of 119 studies were included,and it was found that there was widespread activation in the bilateral frontal areas,hippocampus,superior and middle temporal gyri,and some regions of the thalamus in abnormal brain regions related to sleep disorders and brain regions after exercise intervention.Conclusion Exercise may play an important role in alleviating brain activation abnormalities caused by sleep disorders.
4.Evaluation of the effectiveness of BMRT-HPV for cervical cancer screening
Lüfang DUAN ; Hui DU ; Chun WANG ; Xia HUANG ; Xinfeng QU ; Xianzhi DUAN ; Yan LIU ; Bin SHI ; Wei ZHANG ; Lihui WEI ; L. Jerome BELINSON ; Ruifang WU
Chinese Journal of Obstetrics and Gynecology 2020;55(10):708-715
Objective:Evaluation of the clinical value of the BioPerfectus multiplex real time (BMRT)-HPV for cervical cancer screening.Methods:Physician-collected specimens of 1 495 women who were positive of Cobas 4800 HPV (Cobas-HPV), HPV genotyping based on SEQ uencing (SEQ-HPV), and (or) cytology ≥low grade squamous intraepithelial lesion (LSIL) in the primary screening of Chinese Multiple-center Screening Trial (CHIMUST), and 2 990 women selected from those who were negative of primary screening in the same project through nested control randomization with age-matching were tested for BMRT-HPV, which reported type-specific viral loads/10 000 cells in each specimen. With comparing to Cobas-HPV results and taking cervical histopathological diagnosis as the endpoint, the concordance of high-risk (HR)-HPV subtypes among the three assays was explored ,and the sensitivity and specificity of BMRT-HPV for cervical cancer screening were evaluated.Results:(1) The overall agreenment of HR-HPV subtypes between BMRT-HPV and Cobas-HPV, or SEQ-HPV test sample was 94.8%, 94.4%, with Kappa values 0.827, 0.814. (2) The sensitivity and specificity for cervical intraepithelial neoplasia (CIN) Ⅱ + of BMRT-HPV, Cobas-HPV and SEQ-HPV were 92.62%, 94.26%, 93.44% and 84.67%, 83.25%, 82.76%, respectively. There were no significant difference in sensitivity among the three HPV assays (all P>0.05), but the specificity of BMRT-HPV for CIN Ⅱ + was higher than those of Cobas-HPV and SEQ-HPV ( P<0.01). The sensitivity for CIN Ⅲ + of three HPV assays were all 100.00%, and the specificity for CIN Ⅲ + of BMRT-HPV was higher than those of Cobas-HPV and SEQ-HPV (83.40% vs 81.95%, 83.40% vs 81.50%; P<0.01). The number of pathological examinations of colposcopy for cervical biopsy detected in 1 case of CIN Ⅱ + or CIN Ⅲ + in BMRT-HPV was less than those in Cobas-HPV and SEQ-HPV ( P<0.01). When using HPV 16/18 + cytology ≥atypical squamous cell of undetermined signification (ASCUS) to triage HPV positive women among three assays, there was no different in the sensitivities of detecting CIN Ⅱ + and CIN Ⅲ + ( P>0.05). The specificity BMRT-HPV was slightly higher than those in Cobas-HPV or SEQ-HPV (all P<0.05), and the colposcopy referral rate was lower than those in Cobas-HPV and SEQ-HPV (all P<0.05). Conclusions:BMRT-HPV is as sensitive as Cobas-HPV or SEQ-HPV for primary cervical cancer screening, and has higher specificity. Therefore it could be used as a primary screening method for cervical cancer, which is worthy of clinical application.
5.Effect of health management on blood lipid level and carotid artery plaque in patients with carotid artery stenosis
Jing SUN ; Qiaoling PENG ; Lihui DUAN
Journal of Clinical Neurology 2017;30(4):267-270
Objective To explore effect of health management on blood lipid level and carotid artery plaque in patients with carotid artery stenosis.Methods One hundred and eighty patients with carotid artery stenosis were dived divided into health management group (90 cases) and routine treatment group (90 cases).All the patients took routine treatment, and the health management were given for 12 months continuously in health management group.The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were tested, the carotid artery was checked by carotid artery color Doppler flow imaging before and at 6 months, 12 months after treatment.Results The levels of TC, TG, LDL-C in health management group and routine treatment group at 6 and 12 months after treatment were significantly decreased than those before the treatment , and the level of HDL-C were significantly increased (all P<0.05).There was no significant difference in the levels of TC, TG, HDL-C, LDL-C before and at 6 months between the two groups (all P>0.05).The levels of TC, TG and LDL-C at 12 months after treatment in health management group were significantly decreased than those in routine treatment group, and the level of HDL-C was significantly increased (all P<0.05).There was no significant difference in Crouse plaque integral in health management group and routine treatment group between before and at 6 months after treatment (all P>0.05).The Crouse plaque integral at 12 months after treatment in health management group and routine treatment group were significantly decreased than those before the treatment (all P<0.05).There was no significant difference in Crouse plaque integral before and at 6 months after treatment between the two groups (all P>0.05).Crouse plaque integral at 12 months after treatment in health management group was significantly decreased than that in routine treatment group (P<0.05).Conclusion Long-term health management can decreased the level of serum lipid level and inflammation, and improve the situation of carotid artery plaque.
6.Effect of carotid artery stenting on fatigue and cognitive function in patients with carotid artery stenosis
Lihui DUAN ; Xiangliang CHEN ; Yunyun XIONG ; Xinfeng LIU
Journal of Medical Postgraduates 2015;(4):398-401
Objective Carotid artery stenosis is closely related not only with the cognitive function impairment, but also can cause patients to physical fatigue and a series of consequences.The aim of this study was to investigate the correlation between carotid artery stenting for carotid artery stenosis in patients with cognitive function improvement effect and fatigue and cognitive function in this paper. Methods One hundred cases of clinical data of patients with carotid artery stenosis of carotid artery stentingwere analyze pro-spectively.The cognitive scales of mini mental state examination (mini mental scale state examination, MMSE), Montreal cognitive as-sessment(Montreal cognitive, assessment, MoCA), activities of daily living scale (activities of dailyliving, ADL), fast vocabulary test ( verbal fluency) , Webster's count test, digit span test( working memory) , Digit Symbol Substitution Test ( speed) and the the fatigue scales of fatigue assessment scale-14 ( Fatigue Scale-14, FS-14) , fatigue severity scale ( FatigueSeverity Scale, FSS-9) were observed before and 3, 6 months after surgery.The correlation between fatigue and cognitive impairment was also analyzed Results Operation was successful in all patients, and no serious complications occurred after surgery.Patients'clinical symptoms were significantly im-proved compared with those on admission.MMSE, MoCA, ADL, verbal fluency test, Wechsler arithmetic, digit span and digit symbol substitution test results showed that, the scores were significantly improved compared with those on admission( P<0.05) , and with the time prolonging, cognitive function improved more obviously( P<0.001) .Compared with before operation,FS-14 score [ ( 7.11±1.37) vs (4.38±0.97)] and FSS-9 scores were significantly decreased6 months after operation, [(52.45±6.77) vs (43.29±7.21)](P<0.05). The correlation coefficient of FS-14 and MMSE, FFS 9 and MMSE were -0.357, -0.311 6 months after surgery, and the correlation coefficientof FSS-14 and MoCA, FSS-9 and MoCA were -0.547,-0.351, which showed a significant negative correlation (P<0.05). Conclusion Carotid artery stenting therapy can improve cognitive function and fatigue in patients with carotid artery stenosis, and the effect was more significant with the time prolonging, and there was a certain correlation between fatigue and cognitive impairment.
7.Clinical effect observation of angioplasty for symptomatic intracranial atherosclerotic stenosis
Juan DU ; Qiankun CAI ; Yunyun XIONG ; Qiliang DAI ; Lihui DUAN ; Zhongming QIU ; Fang YANG ; Gelin XU ; Guanghui CHEN ; Xinfeng LIU ; Qin YIN
Chinese Journal of Cerebrovascular Diseases 2014;(4):178-182,191
Objective To investigate the clinical effect of angioplasty for symptomatic intracranial atherosclerotic stenosis. Methods Eighty-two patients with symptomatic intracranial atherosclerotic stenosis whom underwent angioplasty after the failure of standard medical therapy were enrolled from Nan-jing Stroke Registry Program from September 2010 to June 2013.Nine of them underwent routine balloon angioplasty alone and 73 underwent intracranial stenting.The median time from onset to surgery was 24.5 days.The occurrence of endpoint events (any stroke ≤30 d after procedure,death and ischemic stroke >30 d in guilty vessels or original stenosis had restenosis and needed to be treated again)was assessed. The incidence of restenosis was followed up with imaging (CTA or DSA). Results (1)In the 82 patients, the success rate of operation was 92.7%(n=72 ),and 78 (95.1%)received follow-up,4 were lost to follow-up.The median follow-up time was 22.5 months (range 9 to 29 months ).Ten patients had an endpoint event,7 of them were ischemic stroke,1 was cerebral hemorrhage,and two were severe asymptomatic restenosis who underwent stenting again.The endpoint events of 3 patients occurred at day 30 after procedure (at ≤24 h after procedure).Kaplan-Meier curves showed that the incidences of cumulative endpoint events at 1,6,12,and 24 months were 3.7%,8.6%,11%,and 13%,respectively.(2)60 patients (73.2%)received imaging examination (11 CTA and 49 DSA ).Restenosis occurred in 17 patients (28.3%),among them the incidence of symptomatic restenosis was 5%(n =3 ),and asymptomatic restenosis was 23.3%(n=14). Conclusion After a comprehensive assessment and a rigorous screening, the safety is high and the mid- and long-term efficacy are satisfactory in patients with symptomatic intracranial arterial stenosis who are treated with angioplasty when their medical treatment is invalid.
8.Endovascular interventional therapy of acute ischemia stroke: perioperative complications and their treatment
Lihui DUAN ; Wen SUN ; Xiaobing FAN
International Journal of Cerebrovascular Diseases 2013;21(11):832-835
As an effective therapeutic approach for acute ischemic stroke,endovascular interventional therapy has received increasing attention.However,a large number of revascularization clinical trials have shown that its mortality rate and the incidence of complications are higher than intravenous thrombolysis.This article reviews the perioperative complications of endovascular interventional therapy of acute ischemic stroke and thek treatment.
9.Endovascular interventional therapy of acute ischemia stroke: factors affecting therapeutic effect
Lihui DUAN ; Wen SUN ; Xinying FAN
International Journal of Cerebrovascular Diseases 2013;21(11):843-846
Endovascular interventional therapy can signifantly improve the clinical outcomes in patients with acute ischemic stroke.It has become the important therapeutic means and research focus for acute ischemic stroke.However,there are many factors affecting its efficacy.This article reviews the factors affecting the treatment effect of endovascular interventional therapy of acute ischemic stroke.
10.Relationship between chronic kidney disease and cerebral small vessel disease in elderly patients
Hua LI ; Wenxin ZHAO ; Suhong REN ; Fang SUN ; Lihui DUAN ; Bin YAN ; Guoqing ZHOU
Chinese Journal of Geriatrics 2009;28(8):658-660
ObjectiveTo explore the relationship between chronic kidney disease (CKD) and cerebral small vessel disease (SVD) in elderly patients. MethodsOne hundred and fifty-two elderly male CKD patients for experimental group and 158 elderly male for control group were recruited. Demographic data and vascular risk factors were recorded. White matter lesion (WML) was semi-quantitatively assessed by cerebral magnetic resonance imaging (MRI), and lacunar infarction (LI) was also calculated. Results(1) The prevalenees of hypertentsion and diabetes mellitus were higher in elderly CKD patients than those in control group (30. 9% vs. 19.0%, 23.7%vs. 14.6%;both P~0. 05). (2) The percentages of grade 2 and grade 3 WMLs were higher in elderly CKD patients than those in control group (34.9% vs. 24.1%, 25.7% vs. 16.5%;both P<0.05). Prevalence of LI was higher in elderly CKD patients than that in control group (45.4% vs.25.3% ,X2= 13. 70, P<0. 05). The similar Resultswere also obtained except for control subjects with hypertension and diabetes mellitus. (3) The logistic regression analysis showed that age, hypertension and low glomerular filtration rate (GFR) were closely associated with SVD in elderly CKD patients. ConclusionsHypertention and diabetes mellitus are risk factors for CKD in elderly patients. SVD is associated with CKD, and age, hypertension and low GFR may be risk factors for SVD in elderly CKD patients.

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