1.Effect of tRF-1:30 on the expression of inflammatory factors in renal tubular epithelial cells induced by high glucose
Yuwei XIA ; Yunyang QIAO ; Xuewei LIU ; Huimin SHI ; Gaoting QU ; Aiqing ZHANG ; Weihua GAN
Tianjin Medical Journal 2024;52(6):561-566
Objective To investigate the effect and molecular mechanism of tRF-1:30-Gln-CTG-4(tRF-1:30)on the expression of inflammatory factors in high glucose(HG)-induced renal tubular epithelial cells(RTECs).Methods RTECs were divided into the control group,the HG group,the HG+tRF-1:30 mimic group,the HG+tRF-1:30 negative control(NC)group,the HG+si-IKZF2 group and the HG+si-NC group.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression levels of tRF-1:30,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1)and IKAROS family zinc finger protein 2(IKZF2).Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of TNF-α,IL-6 and MCP-1.Protein expression of IKZF2 was detected by Western blot assay.Dual-luciferase reporter assay was used to detect the targeting relationship between tRF-1:30 and IKZF2.Results The expression levels of inflammatory factors were elevated in HG-induced RTECs,and the expression level of tRF-1:30 was decreased(P<0.05).Overexpression of tRF-1:30 significantly decreased expression levels of inflammatory factors in HG-induced RTECs(P<0.05),and the expression level of IKZF2 was significantly increased(P<0.05).Further knockdown of IKZF2 can inhibit the release of inflammatory factors,and the expression level of IKZF2 was down-regulated after overexpression of tRF-1:30.Double luciferase reporting experiment further verified the possible targeting relationship between tRF-1:30 and IKZF2.Conclusion Overexpression of tRF-1:30 inhibits the expression of inflammatory factors in HG-induced RTECs by target binding and negatively regulating the expression of IKZF2.
2.The Influence of Non-High-Density Lipoprotein Cholesterol on the Efficacy of Genotype-Guided Dual Antiplatelet Therapy in Preventing Stroke Recurrence
Qin XU ; Xia MENG ; Hao LI ; Xuewei XIE ; Jing JING ; Jinxi LIN ; Yong JIANG ; Yilong WANG ; Xingquan ZHAO ; Zixiao LI ; Liping LIU ; Anxin WANG ; Yongjun WANG
Journal of Stroke 2024;26(2):231-241
Background:
and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence.
Methods:
This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days.
Results:
Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425).
Conclusion
CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.
3.Therapeutic effects and influencing factors of transcranial direct current stimulation on memory function in patients with Alzheimer′s disease
Yang LIU ; Xuewei XIA ; Zhiqi MAO
Chinese Journal of Neurology 2022;55(5):529-536
Alzheimer′s disease (AD) is a neurological disorder of unknown etiology characterized by memory loss and severe intellectual impairment. Transcranial direct current stimulation (tDCS) acts on the brains of AD patients in a non-invasive manner by reducing neurotoxic substances, promoting synaptic plasticity, producing long-term after-effects, weakening neuroinflammation, and reducing oxidative stress in brain tissue, among other mechanisms that affect patients′ memory functions. Therefore, tDCS has become an important tool to improve the memory of AD patients. And the effect of this treatment on memory improvement is influenced by factors such as stimulation site, current level, and stimulation duration.
4.Clinical effect of navigation assisted neuroendoscope hard channel technology with the assistance for treating hypertensive cerebral hemorrhage in basal ganglia region
Hanxun YAO ; Xuewei XIA ; Jing XIAO ; Wenbo WANG
Chongqing Medicine 2018;47(8):1055-1057
Objective To investigate the effect of navigation assisted neuroendoscope hard channel technology for treating hypertensive cerebral hemorrhage in basal ganglia region.Methods Eighty-two inpatients with hypertensive cerebral hemorrhage in basal ganglia region treated in this hospital were selected as the study subjects,among them 37 cases adopted the neuroendoscope hard channel technology and 45 cases adopted the small bone window craniotomy.The operation time,intraoperative bleeding vol-ume,hematoma clearance rate,postoperative complication occurrence rate and NIHSS score at postoperative 3 months were com-pared between the two groups.Results Compared with the bone window group,the operative time in the endoscopic group was lon-ger and the hematoma clearance rate was higher,intracranial rebleeding occurrence rate was lower and the short term prognosis was better(P<0.05).The aspects of intraoperative bleeding volume and other postoperative complications had no statistically signifi-cant difference between the two groups(P> 0.05).Conclusion The navigation assisted neuroendoscope hard channel technology can improve the cure rate in the patients with hypertensive cerebral hemorrhage in basal ganglia region.
5.Comparison of the inhibition potentials of icotinib and erlotinib against human UDP-glucuronosyltransferase 1A1.
Xuewei CHENG ; Xia LV ; Hengyan QU ; Dandan LI ; Mengmeng HU ; Wenzhi GUO ; Guangbo GE ; Ruihua DONG
Acta Pharmaceutica Sinica B 2017;7(6):657-664
UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risksUGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The ICvalues of icotinib and erlotinib against UGT1A1-mediated NCHN--glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with thevalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risksUGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration-time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risksUGT1A1 inhibition.
6.The differences of memories and sleep parameters and their correlations in patients with insomnia disorder in different subtypes: a clinical study
Qiguo WEI ; Guihai CHEN ; Lan XIA ; Fang WANG ; Xuewei LI
Chinese Journal of Neurology 2015;48(9):763-767
Objective To explore the differences of memory functions and objective sleep parameters and their correlations in patients with insomnia disorder in different subtypes.Methods Eightynine patients with insomnia disorder,including 11 patients with difficulty initiating sleep(DIS),20 patients with early morning awakening(EMA),20 patients with difficulty maintaining sleep (DMS) and 38 patients with mixed sleep symptoms(MS) were enrolled between August 2012 and February 2014 in the Memory and Sleep Disorders Clinic of the First Affiliated Hospital of Anhui Medical University.Memory functions,including objective memory,spatial memory,working memory and reference memory were detected with nine boxes maze,and objective sleep profiles were assessed using polysomnography.Results The error numbers of spatial(H =15.404,P =0.002) and working (H =10.126,P =0.018) memories were significantly different among the 4 subtypes of patients,with more errors of spatial and working memory in the EMA (6.00 (5.00,8.00),5.00 (4.00,6.00)) and MS (5.00 (3.75,7.25),5.00 (2.75,7.00)) groups compared with the DMS (2.50 (2.00,4.00),2.00 (1.00,4.00)) group (tspstial =3.938,3.428;t =2.803,2.840;all P < 0.05).Sleep efficiency(H =7.929,P =0.048),REM sleep time(F =2.840,P =0.043) and the percentage of REM sleep time on total sleep time (REM%;H =7.913,P =0.048) were also significantly different among the 4 subtypes of patients,with lower sleep efficiency in the MS(69.7% (50.5%,78.7%)) group compared with the EMA (81.0% (64.8%,86.4%)) and DMS (80.2% (62.6%,88.9%)) groups (t =2.242,2.352;all P < 0.05),less REM sleep time (min) and REM% in the EMA(61.6 ±27.1,16.9% (13.1%,21.9%)) and MS(56.9 ±31.4,16.9% (11.5%,21.2%)) groups compared with the DMS (80.9 ± 32.7,22.3% (18.5%,25.5%)) group (qREM time =3.791,5.397;tREM% =2.513,2.612;all P <0.05).The error numbers of working memory and spatial memory negatively correlated with the REM sleep time (r =-0.387,-0.348;all P < 0.05) and REM% (r =-0.350,-0.354;all P < 0.05).Conclusions There are discrepancies in the spatial and working memories and subtle differences in the objective sleep parameters among the patients with different subtypes of insomnia disorder.The worse memories in insomnia disorder patients might be associated with the decreased REM sleep.
7.Relationship between deficits of learning and memory and expressions of PSD-95 in hippocampus in traumatic brain injury rats
Xuewei XIA ; Yuwei DONG ; Yiqing DU ; Yongdong YANG ; Puyang LI ; Shuaiqi SUN
Chinese Journal of Trauma 2012;28(2):175-178
ObjectiveTo investigate the relation of learning and memory with the expression of postsynaptic density 95 (PSD-95) in traumatic brain injury (TBI) rats in Morris water maze.Methods Forty adult male Sprague-Dawley rats were randomly assigned to the TBI group and control group.The TBI group was produced using the impact acceleration injury model.Morris water maze memory paradigm was used to assess the learning and memory function in both groups one week after injury.Protein electro-phoresis was used to observe the expression of PSD-95 1,3,7 d after TBI.ResultsCompared with the control group,the TBI group showed a longer latency in the Morris water maze after one week,significantly longer than the latency in the first three days after TBI.The quantification of PSD-95 in the hippocampus was gradually reduced at one week after TBI ( P < 0.01 ).ConclusionTBI may decrease expression of PSD-95 in the hippocampus of the rats,as may be one of the mechanisms for impairments of learning and memory of rats.
8.Mutation analysis of microRNA-7 gene in Chinese patients with Parkinson's disease.
Xuewei ZHANG ; Jifeng GUO ; Sanxi AI ; Yaceng HU ; Qiying SUN ; Qian XU ; Zhanyun LU ; Kai LI ; Xiaoli DONG ; Lu SHEN ; Hong JIANG ; Qian PAN ; Kun XIA ; Xinxiang YAN ; Beisha TANG
Journal of Central South University(Medical Sciences) 2012;37(12):1189-1192
OBJECTIVE:
To investigate the mutation of small sequence changes in microRNA-7 gene in Chinese patients with Parkinson's disease (PD).
METHODS:
We analyzed miR-7 variants in 225 PD patients from Chinese Han group by DNA sequence.
RESULTS:
None of the patients had miR-7 variants.
CONCLUSION
MiR-7 variation is not associated with PD in Chinese patients.
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genetics
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genetics
9.Mutation analysis of PINK1 gene in patients with early-onset Parkinsonism
Xuewei ZHANG ; Hainan ZHANG ; Bing LIAO ; Jifeng GUO ; Kun XIA ; Beisha TANG
Journal of Central South University(Medical Sciences) 2011;36(6):490-497
Objective To determine the frequency of mutations in PINK1 in Chinese Han people with sporadic early-onset Parkinsonism (EOP). Methods DNA sequencing was used to detect point mutations and small deletions/insertions, and quantitative real-time PCR was carried out to detect deletions/insertions and rearrangements in 149 patients and 150 healthy controls. Results Four heterozygous mutations in PINK1 were identified, including 3 missense mutations (c.832C>G, c. 938C>T, c.1 220G>A) and ex 3-8 del. A novel single nucleotide polymorphism (SNP) c.899+18G>A and 14 reported SNPs were identified. Chi-square test showed that c.189C> T and c.960-5G﹥A had significant difference in the genotype frequencies and allele frequencies between the patients and the controls (for c.189C>T genotype χ2=21.244,P<0.0001; T allele χ2=24.353,P<0.0001, and for c.960-5G﹥A genotype's χ2=6.524,P =0.038; A allele χ2=6.725,P=0.0095). Conclusion About 3.35% Chinese Han patients with EOP carry mutations in PINK1. Two SNPs c.189C>T and c.960-5G>A may contribute to the risk of EOP in Chinese Han people.
10.Analysis of parkin gene mutations in Han Chinese with sporadic early-onset parkinsonism in southern China
Liluo NIE ; Jifeng GUO ; Hainan ZHANG ; Xuewei ZHANG ; Lei WANG ; Linzi LUO ; Lu SHEN ; Hong JIANG ; Kun XIA ; Beisha TANG ; Xinxiang YAN
Chinese Journal of Neurology 2010;43(10):692-696
Objective To investigate the spectrum and features of parkin gene mutations in Chinese patients with sporadic early-onset Parkinsonism (EOP) in southern China.Methods All 156 Han Chinese patients with sporadic EOP were screened for mutations in parkin gene using SYBR Green Ⅰ Real-time PGR combined with sequencing of the entire coding region of the gene.Results Nineteen cases carried parkin mutations, including 2 homozygous, 2 compound heterozygous and 15 heterozygous mutations.Seventeen parkin gene rearrangement mutations ( 12 exon deletions and 5 exon duplications) and three small sequence mutations (ⅣS9 + 18C > T,c.202-203delAG and c.813delT) were identified.The c.813delT is a novel mutation.The segment between exon 1 and 7 are mutational hot spot.Cases with parkin mutations showed no difference in initial symptoms, cardinal symptoms and disease severity, compared with cases without parkin mutations.But patients with parkin mutations showed significant earlier onset age ( ( 40.9 ± 6.8 ) years vs (35.5 ± 10.0) years, Z = -2.271, P <0.05) and longer disease duration ( (4.4 ±3.6) years vs (7.6 ±4.0) years,Z = - 3.680, P < 0.05 ) than those without parkin mutation.Conclusions The frequency of parkin gene mutation was 12.18% in Han Chinese patients with sporadic EOP.Rearrangement mutation may be the predominant type of mutations.The exon deletion is a main mutation style.The sequence fragment between exon 1 and 7 of the parkin gene are mutational hot spots.There were no significant differences in clinical features between cases with parkin mutation and those without.However, our patient with parkin mutations showed a significantly earlier onset age, longer disease duration and slower progression than those without parkin mutation.

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