1.Effects of Nrf2-ARE signal path on levrtiracetam anti-epileptic andlevrtiracetam on learning and memorizing ability
Ke WU ; Wenli ZHAO ; Yueying LI ; Changyu QIU ; Haijing SHI ; Yongmei ZHANG
Chinese Pharmacological Bulletin 2017;33(10):1462-1466
Aim To explore the effects of Nrf2-ARE signal path on levrtiracetam anti-epileptic and levrtiracetam on learning and memorizing ability.Methods Thirty-six SD rats were divided into normal saline group, levrtiracetam group, model group and treatment group.Each group recruited nine rats.Tests of Morries water maze were given to the rats to evaluate their learning and memorizing ability.The protein expression of nuclear factor (erythroid-derived2)-like2 (Nrf2), heme oxygenase 1(HO-1) and NAD(P)H quinone oxidoreductase(NQO1) were examined by Western blot.Results Compared with model group, levrtiracetam could shorten the plateau period in epileptic rats (P<0.05), and increase the expression of Nrf2 protein, HO-1 protein and NQO1 protein in hippocampus(P<0.05).Conclusions Levrtiracetam could improve the learning and memorizing ability in epileptic rats.Levrtiracetam may increase the expression of HO-1 protein and NQO1 protein through the Nrf2-ARE pathway and play a part in antiepileptic effects.
2.The Influence of Head-down Tilt on the Visual Evoked Potential of Healthy People
Jun ZHAO ; Lianna HU ; Zhisheng LI ; Huize LIANG ; Hongxin YAN ; Changyu QIU
Space Medicine & Medical Engineering 2006;0(03):-
Objective To observe the influence of head-down tilt on visual evoked potential.Methods Six healthy volunteers were exposed to-6? head-down tilt.The visual evoked potential were measured before the test,the second day and the fifth day of the test under different space frequency.Results No significant difference was found in the latency of P100 before and after the test.The amplitude of P100 had significant change under high space frequency.But not the same happened on middle and low space frequency.Conclusion head-down tilt can induce the change of visual evoked potential under high space frequency,which means the weightlessness may influent the visual function.
3.The influence of head down tilt on electroretinography
Jun, ZHAO ; Lianna, HU ; Zhisheng LI ; Huize, LIANG ; Hongxin, YAN ; Changyu, QIU
Chinese Ophthalmic Research 2010;28(2):172-174
Background Influence of weightlessness on visual function has been a hot topic in aerospace medicine field.Electroretinography (ERG) is valuable tool of evaluating visual function.Objective This study aims to observe the influence of head down tilt simulated weightlessness on ERG.MethodHead down tilt for 6° was adopted in 6 healthy volunteers.Flash ERG,including rod response,maxium response,cone response,oscillatory potentials (OPs) and 30 Hz flicker was recorded,and the latency and amplitude from each wave were analyzed before,two days and five days after trial.The record procedure followed the ISCEV standard for full field clinical electroretinography (2008 update).Oral informed consent was obtained from all the subjects prior to the trail.Results No significant differences were detected in the latencies and amplitudes of a,b waves of cone response and 30 Hz flicker among various time points(P>0.05).The latencies were significantly prolonged in b wave of rod and a,b waves of maxim responses(P<0.01),but no obvious change was found in amplitudes (P>0.05).Both the latency and amplitude of all of the wavelets of OPs were considerably among the different time points(P<0.05-0.01),and the ∑OPs was evidently different among the different time points(P<0.05).Conclusion Head down tilt simulated weightlessness induce the abnormality of visual function in the early stage.
4.Prognosis of huge hepatocellular carcinoma after hepatectomy
Changyu LI ; Funan QIU ; Yaodong WANG
Chinese Journal of General Surgery 2021;36(11):817-821
Objective:To evaluate the risk factors on prognosis after resection of huge hepatocellular carcinoma.Methods:The clinical and followup data of 146 patients undergoing radical resection at Fujian Province Hospital from Jan 2012 to Dec 2017 was analyzed retrospectively.Results:Independent risk factors for tumor recurrence were neutrophil/lymphocyte ratio ≥2.49, serum alpha-fetoprotein ≥400 ng/ml, non-anatomical hepatectomy, ruptured huge hepatocellular carcinoma, multiple tumor and microvascular invasion and macrovascular invasion. These seven factors were used to develop a risk prediction model, in which 1-year recurrence-free rates in patients with low, middle, high risk group were 68.5%, 23.5%, and 0, respectively, and 3-year recurrence-free rates were 34.2%,15.3% and 0, respectively. Independent risk factors for tumor overall survival were neutrophil/lymphocyte ratio≥2.49, serum alpha-fetoprotein ≥400 ng/ml, HBV-DNA ≥2 000 IU/ml, multiple tumor, microvascular invasion, macrovascular invasion and hepatic capsule invasion. These seven factors were used to develop a risk prediction model, in which 1-year survival rates in patients with low, middle, high risk group were 94.7%, 74% and 40%, respectively, and 3-year survival rates were 68.4%,30.1%, and 5.7%, respectively.Conclusions:The recurrence rate of patients with huge hepatocellular carcinoma is high. Independent risk factors affecting prognosis were high neutrophil/lymphocyte ratio, high AFP level, high HBV-DNA, non-anatomical hepatectomy,ruptured,multiple tumor, microvascular and macrovascular invasion.
5.Comprehensive analysis of differential methylation genes in cholangiocarcinoma and identification of prognosis-related genes glucosaminyl (N-acetyl) transferase 1 and neurotrophic receptor tyrosine kinase 3
Changyu LI ; Hong SUN ; Yangyang HUANG ; Zixin HE ; Wenbin HE ; Zhangwei CHENG ; Funan QIU ; Yaodong WANG
Cancer Research and Clinic 2022;34(8):569-575
Objective:To identify and screen the differential methylation genes in patients with cholangiocarcinoma and to predict the prognosis of patients with CCA.Methods:Cholangiocarcinoma tissues and paracancerous tissues of 8 patients with cholangiocarcinoma in Fujian Provincial Hospital from October 2019 to May 2020 were selected for 850K methylation sequencing analysis to obtain differentially methylated genes. The 2018 genome-wide methylation data and clinical information of 36 patients with cholangiocarcinoma were download from The Cancer Genome Atlas (TCGA) database, the 2012 cholangiocarcinoma methylation data (GSE32879) were download from the Gene Expression Omnibus (GEO) database, and the 2018 TCGA database differential survival genomic data of overall survival (OS) and disease-free survival (DFS) of cholangiocarcinoma were download from the GEPIA2 database. The differentially methylated positions (DMP) and differentially methylated regions (DMR) results of 850K methylation sequencing analysis of submitted samples, methylated genes in TCGA and GEO databases, and cholangiocarcinoma survival genes of samples were jointly submitted for testing, multi-data set analysis was performed by the Sangerbox VENN tool, and common differentially methylated genes were obtained by intersection screening. The minimum P value method was used to determine the cut-off value of gene expression in Sangerbox, and the patients were divided into high and low expression groups of differentially methylated genes. The OS, DFS, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI) of cholangiocarcinoma patients were compared between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Results:A total of 121 954 DMP were identified by 850K methylation sequencing of cholangiocarcinoma tissues and paracancerous tissues of 8 patients; a total of 1 399 differentially methylated genes were identified in DMR, and the common prognosis related genes glucosaminyl (N-acetyl) transferase 1 (GCNT1) and neurotrophic receptor tyrosine kinase 3 (NTRK3) were identified by intersection identification. The expression of GCNT1 in the cholangiocarcinoma tissues was higher than that in the paracancerous tissues, and the difference was statistically significant ( P = 0.040). The expression of NTRK3 in cholangiocarcinoma tissues was higher than that in the paracancerous tissues, but the difference was not statistically significant ( P = 0.790). The minimum P value method was used to predict the prognosis of patients with cholangiocarcinoma based on the combined expression of GCNT1 and NTRK3, and the order was based on the sum of the expression levels of the two genes. When 30% of the ranking was taken as the cut-off value, the difference in DFS between the high expression group and the low expression group in cholangiocarcinoma was the most significant ( P < 0.001); there was no significant difference in OS between the two groups ( P = 0.065). The results of GO functional analysis showed that GCNT1 was involved in protein glycosylation, macromolecule glycosylation, glycosylation, glycoprotein biosynthetic process, glycoprotein metabolic process, transferase activity and transferring glycosyl groups, protein O-linked glycosylation, O-glycan processing, etc., and NTRK3 was involved in neurotrophin signaling pathway, Ras signaling pathway, EGFR tyrosine kinase inhibitor resistance, ErbB signaling pathway, phospholipase D signaling pathway, central carbon metabolism in cancer, natural killer cell mediated cytotoxicity, etc. The results of KEGG analysis showed that GCNT1 was mainly associated with system functions such as mucin-type O-glycan biosynthesis and metabolic pathways, and NTRK3 was mainly associated with cell surface receptor pathways, intracellular signal transduction, positive regulation of stimulatory responses, transmembrane receptor protein tyrosine kinase signaling pathway, enzyme-linked receptor protein signaling pathway, MAPK signaling pathway cascade and regulation, protein phosphorylation signal transduction and other system functions. Conclusions:The expressions of differentially methylated genes GCTNT1 and NTRK3 in cholangiocarcinoma have certain predictive effects on the prognosis of patients with cholangiocarcinoma.
6.Observation and analysis of systemic reactions to house dust mite subcutaneous immunotherapy in 362 patients with allergic rhinitis
Jianrong XUE ; Jing MA ; Changyu QIU ; Zhibang HU ; Xing JIANG ; Min PAN ; Meiping LU ; Lei CHENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(5):445-451
Objective:To investigate the frequency and severity of systemic reactions (SRs) to standardized house dust mite subcutaneous immunotherapy (SCIT) in patients with perennial allergic rhinitis (AR), and to analyze the clinical risk factors.Methods:The clinical data of 362 patients including 209 males and 153 females, aged from 5 to 55 years old receiving SCIT at the Department of Otorhinolaryngology, the Third People′s Hospital of Changzhou were collected from May 2014 to July 2017. The SRs were classified as early-onset and delayed-onset, and 4 grades (grade Ⅰ to Ⅳ) to assess severity. The records of SRs were retrospectively analyzed, including the numbers/frequencies, symptoms and signs, onset of reaction and treatment. And the relationships between SRs and patient′s age, gender, allergen injection dose, accompanied allergic diseases were explored. All the statistical analyses were conducted using SPSS 19.0.Results:There were 57 cases (15.75%) of SRs in 362 patients. All the patients received a total of 12 308 injections and 111 SRs (0.90%) were observed. Among them, 31 (27.93%) were early-onset reactions and 80 (72.07%) were delayed-onset reactions; most of the SRs were grade Ⅰ reactions ( n=83, 74.78%), followed by grade Ⅱ ( n=25, 22.52%), grade Ⅲ ( n=3, 2.70%), and no fatal reactions occurred. The incidence of SRs in patients>14 years old was higher than that in patients ≤14 years old according to the number of cases and injections (35.14% vs 13.54%, 2.34% vs 0.76%, χ 2 value was 11.679, 28.162, respectively, all P<0.05), but no significant differences of SRs were observed in gender (18.66% vs 11.76%, 5.98% vs 5.62%, χ 2 value was 3.166, 0.095, respectively, all P>0.05). Fifteen SRs (13.51%) occurred during the build-up phase and 96 (86.49%) during the maintenance phases. SRs could occur in lots of dose phases, and 95 (85.59%) were distributed at high concentrations more than 40 000 SQ-U. The incidence of SRs in patients with multiple allergic diseases was significantly higher than that in patients with AR alone, with asthma or atopic dermatitis (30.67% vs 11.85%, χ 2=15.875, P<0.001). Meanwhile, the incidence of SRs in patients with pure AR was also significantly lower than that in patients with other allergic diseases (5.26% vs 20.56%, χ 2=13.783, P<0.001). Conclusions:The incidence of SRs is less than 1% according to the injection times, the severity of SRs is mostly slight, and the safety and tolerance are good during standardized house dust mite SCIT in perennial AR patients. Delayed-onset SRs are more common. The incidence of SRs is significantly correlated with age, high dose of allergen vaccine injection, and concomitant other allergic diseases (asthma, atopic dermatitis, etc).
7.The role of NLRP3 signaling pathway in allergic rhinoconjunctivitis
Yubo GONG ; Xiaohua GUO ; Wen-Jun LU ; Yuanchao LI ; Changyu QIU ; Yuanyuan SHI ; Liping XIA ; Lin SHI ; Wei WU ; Ling LUO
The Journal of Practical Medicine 2024;40(14):1922-1927
Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.