1.Sumatriptan down-regulates calcitonin gene-related peptide expression via extracellular signalregulated 1/2 and c-Jun N-terminal kinase signaling transduction pathways in rat trigeminal ganglion after organ culture
Guogang LUO ; Bobo YUAN ; Wenjing FAN ; Xingyun YUAN ; Kang HUO ; Shemin LV ; Yongxiao CAO ; Cangbao XU
Chinese Journal of Neurology 2012;45(7):511-515
Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P < 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P <0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It suggests that the optimal concentration of sumatriptan significantly down-regulates CGRP over-expression via intracellular ERK1/2 and JNK signaling transduction pathways in TG after organ culture.
2.The pharmacological mechanism of gastrodin on calcitonin gene-related peptide of cultured rat trigeminal ganglion.
Guogang LUO ; Wenjing FAN ; Xingyun YUAN ; Bobo YUAN ; Shemin Lü ; Yongxiao CAO ; Cangbao XU
Acta Pharmaceutica Sinica 2011;46(12):1451-6
The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.
3.Clinical analysis of headache in patients with cerebral venous sinus thrombosis
Xiangjun DOU ; Guogang LUO ; Xingyun YUAN ; Qiang ZHANG ; Liyun ZHANG ; Jingjie LIU ; Qiuli ZHANG
Chinese Journal of Cerebrovascular Diseases 2014;(5):246-249
Objective To analyze the characteristics of the common first attack of headache in patients with cerebral venous sinus thrombosis (CVST). Methods The clinical data of 51 patients who were diagnosed as CVST with MR venography (MRV)or DSA were collected retrospectively. The patients were divided into either a acute group (≤3 week,n= 32)or a chronic group (>3 weeks, n=19). Results (1)The age of onset of symptoms in these patients was 20 to 40 years,and most of them were females. Of all the first symptoms,headache ranked first,accounting for 84. 3%(43/51 );headache only accounted for 52. 9%(27/51 ),headache with other symptoms (ophthalmic symptoms, hemiplegia,and aphasia,etc. )accounted for 31. 4%(16/51 ),and other symptoms such as epilepsy, paralysis,and ophthalmic symptoms accounted for 15. 7%(8/51). (2)The proportion of headache only as the first symptom in the acute group was higher than that in the chronic group (65. 6% vs. 31. 6%,P<0. 05), and the proportion of chronic headache with other symptoms as the first symptom in the chronic group was higher than that of the acute group (P<0. 05). In addition,the proportion of the first symptom including ophthalmic manifestations in the chronic group was higher than that of the acute group (P <0.01 ). (3)Forty-three patients with headache,dull headache or distensible pain accounted for 72. 1%(31/43), thunderclap headache accounted for 11. 6%(5/43),and other kinds of headache accounted for 16. 3%(6/43),however,there were no significant differences about the types of headache between the two groups (all P>0. 05 ). Conclusion Young patients without previous history of migraine,especially women of childbearing age with sudden onset and progressive worsening headache,and the patients with idiopathic intracranial hypertension,CVST should be considered as an important possibility.
4.Mechanical thrombectomy via carotid artery salvage puncture for acute anterior circulation large vessel occlusive stroke: a clinical analysis of 8 cases
Bobo YUAN ; Li YAO ; Weiwang LI ; Xingyun YUAN
Chinese Journal of Neuromedicine 2024;23(8):799-805
Objective:To investigate the efficacy and feasibility of mechanical thrombectomy (MT) via carotid artery salvage puncture in patients with acute anterior circulation large vessel occlusive stroke. Methods:A retrospective analysis was performed. Eight patients with acute anterior circulation large vessel occlusive stroke underwent MT via carotid artery salvage puncture in Departments of Neurology, First People's Hospital of Xianyang, Xi'an Ninth Hospital, Xi'an Daxing Hospital and XD Group Hospital from June 2021 to September 2023 were enrolled. Occlusion location, time from onset to femoral artery puncture, causes of carotid artery salvage puncture, time from femoral artery puncture to carotid artery salvage puncture, time from successful carotid artery puncture to vascular recanalization, modified thrombolysis in cerebral infarction (mTICI) score immediately after MT, and scores of National Institutes of Health Stroke Scale (NIHSS) 24 h after MT and modified Rankin Scale (mRS) 90 d after MT were analyzed. Results:Of the 8 patients, 7 had M1 segment occlusion and 1 patient had M2 segment occlusion. Direct thrombectomy was not possible resulting from type III aortic arch in 3 patients, aortic arch replacement in 1 patient, right common carotid artery twisting angle in 1 patient, left common carotid artery twisting angle in 2 patients, and bilateral femoral artery occlusion in 1 patient. All 8 patients had successful carotid artery puncture under local anesthesia, including 7 with mTICI 3 and 1 patient with mTICI 2b. Average time from successful carotid artery puncture to vascular recanalization was about 35 min, ranged 10-90 min. All patients had decreased NIHSS score 24 h after MT compared with before MT, and no complications such as hematoma or airway compression occurred in carotid artery puncture site. Six patients had mRS scores of 0-2 and 2 had scores of 6 (death cause: pulmonary infection) 90 d after surgery.Conclusion:For patients with patients with acute anterior circulation large vessel occlusive stroke, MT via carotid artery salvage puncture is a safe and feasible method in cases of difficulty in establishing thrombectomy route via femoral artery such as type III aortic arch, common carotid artery twisting angle, abdominal aorta occlusion.
5.Relationship between serum UA level and early outcome in acute ischemic stroke patients
Meimei HAO ; Chen CHEN ; Xingyun YUAN ; Kang HUO ; Jianfeng HAN ; Wenfeng SONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2019;21(5):515-518
Objective To study the relationship between serum UA level and early outcome in acute ischemic stroke (AIS) patients. Methods Four hundred and twenty-one AIS patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2015 to March 2016 were divided into good outcome group (n = 232) and poor outcome group (n = 189) according to their modified Rankin scale (mRS) score. Their demographic data, risk factors for vascular disease, laboratory testing parameters, imaging and clinical data and NIHSS score were recorded and compared. The relationship between serum UA level and early poor outcome in AIS patients was analyzed by unconditioned logistic regression analysis. Results The incidence of AF and cerebral infarction in the territory of anterior cerebral artey and middle cerebral artery, SBP, serum TC,LDL and urea levels,NIHSS and mRS score, and mortality were significantly higher and the hospital stay time was significantly longer while the serum UA level and GCS score were significantly lower in poor outcome group than in good outcome group (P<0.05,P<0.01). Unconditioned logistic regression analysis showed that SBP,NIHSS score and serum UA level were the major risk factors for the early poor outcome in AIS patients (OR = l.017,95%CI:1.003-1.031,P = 0.018;OR = 1.274,95%CI:1.178-1.378,P=0.000;OR=0.993,95%CI:0.989-0.996, P = 0.000). Conclusion The low serum UA level is related with the early poor outcome in AIS patients.
6.Correlation between interleukin 1β-511C/T polymorphism and essential hypertension in the Yi ethnic group of Yunnan province
Tong YANG ; Yuan XU ; Xingyun PU ; Yiting MA ; Jing YANG ; Xin SHU ; Hongyu PENG ; Yanrui WU ; Li LONG
Basic & Clinical Medicine 2024;44(12):1651-1655
Objective To investigate the correlation between interleukin 1β gene-511C/T polymorphism of and essential hypertension in the Yi ethnic group of Yunnan province.Methods-511C/T polymorphism of interleukin 1β gene was detected by PCR-RFLP in 85 Yi patients with essential hypertension(EH group)and 106 Yi healthy people(control group)in Shuanghe Township,Jinning County,Yunnan Province.Genotype and allele frequencies were analyzed by SPSS 27.0 software,and association analysis was performed.Results The frequency distribution of CC,CT and TT genotypes at the mutation site 511 of the IL-1βgene in EH group was 18.82%,44.71%and 36.47%,respectively,and it was 5.66%,26.42%and 67.92%in the control group.The difference in genotype frequency between the two groups was statistically significant(P<0.05).The allele frequency of C and T in EH group was 41.18%and 58.82%,respectively,and the allele frequency of C and T in control group was 18.87%and 81.13%.The frequency difference of alleles between the two groups was statistically significant(P<0.05).Both genotype frequency and allele frequency found in males and females had statistical differences(P<0.05).Conclusions The distribution of IL-1β gene-511C/T polymorphism is related to the incident of essential hyper-tension among the Yi ethnic group Yunnan Province,and is the susceptibility gene of the Yi ethnic group to essen-tial hypertension.
7.Beta-sitosterol improves cerebral ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress
Xingyun YUAN ; Fei WANG ; Wanhong CHEN ; Wenqiang LI ; Juanli ZHANG ; Qing LIU ; Jialun XIN ; Li YAO
Chinese Journal of Neuromedicine 2024;23(9):886-894
Objective:To reveal the effect of β-sitosterol on cerebral ischemia-reperfusion injury (CIRI) in rats and whether its mechanism is related to endoplasmic reticulum stress (ERS).Methods:Fifty-three CIRI rats (CIRI models established by modified Longa method) were randomly divided into model group ( n=14), β-sitosterol low-dose group ( n=13), β-sitosterol medium-dose group ( n=13) and β-sitosterol high-dose group ( n=13); 12 rats underwent the same operation without blocking the middle cerebral artery were selected as sham-operated group. Rats in the sham-operated group and model group were given intragastric administration of 1 mL 5 g/L sodium carboxymethyl cellulose daily. Rats in the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group were given intragastric administration of 1 mL β-sitosterol at 10, 20 and 40 mg/kg/d (dissolved in 5 g/L sodium carboxymethyl cellulose), respectively, for 14 consecutive d. Neurological function was evaluated according to Zea Longa 5 method. Rats were sacrificed and brain tissues were collected. Volume of cerebral infarction was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Brain injury and neuronal apoptosis were evaluated by HE staining, Nissl staining and TUNEL. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) contents were detected by water-soluble tetrazolium 1 (WST-1) method, colorimetric method or thiobarbituric acid (TBA) method, respectively. The mRNA and protein expression levels of protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE-1), activated transcription factor-6 (ATF-6), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and Caspase-12 in the brain tissues were detected by qRT-PCR or Western blotting. Results:Compared with the sham-operated group, the model group had significantly increased neurological function score, cerebral infarction volume and TUNEL positive rate, decreased SOD and GSH-Px content, increased MDA content, and increased mRNA and protein expressions of PERK, IRE-1, ATF-6, GRP78, CHOP and Caspase-12 ( P<0.05). Compared with the model group, the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased neurological function score, cerebral infarction volume, and TUNEL positive rate, increased SOD and GSH-Px content, and decreased MDA content ( P<0.05); the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased mRNA and protein PERK expressions (mRNA: 2.17±0.17, 1.79±0.07 and 1.33±0.07; protein: 5.11±0.52, 2.91±0.26 and 1.98±0.17), IRE-1 expressions (mRNA: 1.75±0.18, 1.65±0.08 and 1.32±0.08; protein: 5.00±0.31, 4.05±0.27 and 1.98±0.14), ATF-6 expressions (mRNA: 2.24±0.12, 1.77±0.14 and 1.37±0.13; protein: 4.93±0.45, 4.04±0.30 and 3.10±0.20), GRP78 expressions (mRNA: 2.67±0.16, 2.11±0.16 and 1.69±0.11; protein: 5.02±0.38, 2.97±0.26 and 2.05±0.22), CHOP expressions (mRNA: 2.01±0.16, 1.70±0.19 and 1.40±0.10; protein: 4.92±0.39, 4.02±0.27 and 3.08±0.22) and Caspase-12 expressions (mRNA: 1.85±0.09, 1.61±0.09 and 1.30±0.09; protein: 3.03±0.20, 2.19±0.11 and 1.82±0.11) compared with the model group (mRNA: 2.99±0.28, 2.27±0.12, 2.57±0.21, 3.46±0.20, 2.50±0.23 and 2.35±0.16; protein: 6.98±0.48, 6.03±0.58, 5.98±0.63, 7.10±0.45, 6.00±0.53 and 5.02±0.43, P<0.05). Conclusion:β-sitosterol attenuates CIRI in rats, whose mechanism may be related to inhibition of ERS signal pathway.
8.Informationization and development strategy in blood collection and supply institutions in Beijing
Yan WANG ; Yong WANG ; Yao YUAN ; Yanli WAN ; Xin SHI ; Xingyun LEI
Chinese Journal of Blood Transfusion 2024;37(11):1307-1312
[Objective] To investigate and analyze the current status, needs and issues of information system construction in blood collection and supply institutions in Beijing, and to provide strategic suggestions for the further improvements. [Methods] The qualitative information of information systems from relevant departments of Beijing Red Cross Blood Center, central blood stations, blood banks and hospitals in Beijing were collected by sequential interview method, and analyzed. [Results] There were 6 information systems in operation in blood collection and supply institutions in Beijing, covering functions such as blood collection and supply service management, blood donation information inquiry and reporting, blood collection and supply institution business management, blood donor information management, blood information promotion and information disclosure. However, there were still issues such as low level of system informatization, lack of top-level design for information construction, non-unified data standards, and incomplete system analysis and statistical functions. [Conclusion] Blood collection and supply institutions in Beijing need to further carry out network infrastructure construction, reconstruct system architecture, improve the functions of the blood management information platform, unify data and interfaces to achieve information sharing, and use emerging technologies to achieve intelligence and precision in blood collection and supply services and management.