基质金属蛋白酶-7血清水平及其基因-181A/G多态性对颈动脉斑块稳定性的影响

Objective To explore the influence of plasma matrix metalloproteinase-7 ( MMP-7 ) levels and genetic polymorphism of MMP-7 - 181 A/G on the stability of carotid plaque.Method According to carotid ultrasound examination, 503 patients with carotid atherosclerotic lesions were consecutively recruited and divided into vulnerable plaque group (n = 118) and stable plaque group (n = 385).Plasma MMP-7 levels were measured by enzyme-linked immunosorbent assay (ELISA), and MMP-7 -181 A/G genotypes were determined by polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP).Results Plasma MMP-7 levels in carotid vulnerable plaque group were significantly enhanced as compared to stable plaque group (t =5.49, P =0.00).The frequency of MMP-7 -181G allele in vulnerable plaque group was significantly higher than that in stable plaque group (11.4% vs 7.0% ,χ2 = 4.78, P= 0.029).Compared to AA genotype, the genotypes with - 181G allele (AG + GG) significantly increased susceptibility to carotid vulnerable plaque ( χ2 = 5.01, OR = 1.81, P = 0.025 ) .When further analyzing the relationship between genotype and plasma MMP-7 levels, no significant differences of plasma MMP-7 levels were observed between AA genotype and AG + GG genotype in stable plaque group.However, in vulnerable plaque group, plasma MMP-7 levels of AG + GG genotype were significantly higher than that of AA genotype( t = 2.62, P = 0.01).Conclusion The present findings suggest that plasma MMP-7 level may be a biomarker for carotid vulnerable plaque.Genetic polymorphism of - 181 A/G in MMP-7 promoter may affect the expression of MMP-7, and seems to be implicated in susceptibility to carotid vulnerable plaque.     

基质金属蛋白酶-7血清水平及其基因-181A/G多态性对颈动脉斑块稳定性的影响

目的 探讨基质金属蛋白酶-7(matrix metalloproteinase-7,MMP-7)血清水平及其基因启动子区-181 A/G多态性对颈动脉斑块稳定性的影响.方法 503例患有颈动脉粥样硬化性疾病的患者根据B型超声检查结果分为颈动脉易损斑块组(118例)和稳定斑块组(385例).采用ELISA法检测两组患者血清MMP-7水平,同时运用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)分析两组患者MMP-7基因启动子-181A/G多态性.结果 易损斑块组血清MMP-7水平为(19.31 ± 8.10)μg/L,而稳定斑块组为(14.98±4.97)μg/L,两者相比差异有统计学意义(t=5.49,P=0.00).MMP-7基因启动子-181位点AG+GG基因型及G等位基因总体分布在易损斑块组和稳定斑块组间比较差异有统计学意义(OR=1.81,P=0.025和OR=1.71,P=0.029).易损斑块组内AG+GG基因型患者血清MMP-7水平较从基因型者高(t=2.62,P=0.01),而稳定斑块组内AG+GG基因型和AA基因型间MMP-7血清水平相比差异无统计学意义(t=6.51,P=0.52).结论 血清MMP-7水平可能成为颈动脉易损斑块检测的一个生物学指标.MMP-7基因启动子区-181A/G多态性可能影响MMP-7蛋白的表达,从而与颈动脉易损斑块的遗传易患性密切相关.

Abstract：

Objective To explore the influence of plasma matrix metalloproteinase-7 ( MMP-7 ) levels and genetic polymorphism of MMP-7 - 181 A/G on the stability of carotid plaque.Method According to carotid ultrasound examination, 503 patients with carotid atherosclerotic lesions were consecutively recruited and divided into vulnerable plaque group (n = 118) and stable plaque group (n = 385).Plasma MMP-7 levels were measured by enzyme-linked immunosorbent assay (ELISA), and MMP-7 -181 A/G genotypes were determined by polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP).Results Plasma MMP-7 levels in carotid vulnerable plaque group were significantly enhanced as compared to stable plaque group (t =5.49, P =0.00).The frequency of MMP-7 -181G allele in vulnerable plaque group was significantly higher than that in stable plaque group (11.4% vs 7.0% ,χ2 = 4.78, P= 0.029).Compared to AA genotype, the genotypes with - 181G allele (AG + GG) significantly increased susceptibility to carotid vulnerable plaque ( χ2 = 5.01, OR = 1.81, P = 0.025 ) .When further analyzing the relationship between genotype and plasma MMP-7 levels, no significant differences of plasma MMP-7 levels were observed between AA genotype and AG + GG genotype in stable plaque group.However, in vulnerable plaque group, plasma MMP-7 levels of AG + GG genotype were significantly higher than that of AA genotype( t = 2.62, P = 0.01).Conclusion The present findings suggest that plasma MMP-7 level may be a biomarker for carotid vulnerable plaque.Genetic polymorphism of - 181 A/G in MMP-7 promoter may affect the expression of MMP-7, and seems to be implicated in susceptibility to carotid vulnerable plaque.     

Plasma fibrinogen beta-148C/T gene polymorphism in cerebral infarction patients

BACKGROUND： Plasma fibrinogen （Fg） β-148C/T gene polymorphism is a risk factor for ischemic angiopathy. OBJECTIVE： To explore the frequency distribution of Fg β- 148C/T gene polymorphism and its relationship with plasma Fg levels in patients with cerebral infarction. DESIGN, TIME AND SETTING： Case control experiment of gene polymorphism was performed at the Central Laboratory of Qingdao University Medical College from January 2003 to June 2004. PARTICIPANTS： A total of 88 patients with cerebral infarction were recruited from the Affiliated Hospital of Qingdao University Medical College, including 52 males and 36 females, averaging （61±14） years of age In addition, 80 healthy cases served as the control group, comprising 48 males and 32 females, with an average age of （58 ± 12） years. METHODS： Blood DNA was extracted, and electrophoresis results were observed using an ultraviolet single photon image system. The frequency distribution of Fg β -148C/T was analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Plasma Fg levels were measured by cerebral infarction time. MAIN OUTCOME MEASURES： Plasma Fg β -148C/T gene polymorphism and plasma Fg levels in patients with cerebral infarction. RESULTS： The frequency of the T allele, and plasma Fg levels in CC, CT, and CC＋CT genotype subgroup, were significantly greater in the cerebral infraction group, compared with the control group （P 〈 0.05）. However, there was no significant difference between the TT genotype subgroup and the control group （P 〉 0.05）. The plasma Fg levels in the CT, TT, and CT＋TT genotype groups were significantly greater than the CC genotype group （P 〈 0.05）. However, in the control group, plasma Fg levels in the TT genotype subgroup were significantly greater than the remaining genotype subgroups （P 〈 0.05）. CONCLUSION： Plasma Fg β -148C/T gene polymorphism is an important hereditary factor for differences in plasma Fg levels. The T allele plays a crucial ro     

Apopotic gene Bax expression in carotid plaque

The expression of BAX in carotid atherosclcrosis and its regulation is far from defined. Objectives To investigate BAX expression in stable/fibrous and instable/vulnerable carotid plaque and its clinical significance. Methods 25 cases of carotid plaque specimens obtained from endarterectomy were divided into two groups, stable/fibrous 14 cases, vulnerable/instable 11 cases; aortic artery and its branches from hepatic transplantation donors 6 case as control. The expression of proapoptotic BAX was detected by immunohistochemistry (IHC), in situ hybridization(ISH) and in situ TdT dUTP nick end labeling (TUNEL). Results 5 eases of BAX ( ) were detected by ICH and ISH, 4 case of TUNEL ( ) were detected by TUNEL in stable/fibrous carotid plaque, while 10 cases were BAX ( )by IHC(P<0.05) , 11 case by ISH and 9 case by TUNEL were detected in instable/vulnerable carotid plaque (P<0.01), respectively. The intensity of BAX ( ) cells by IHC and ISH was 8.63±2.62 and 10.32±3.12 in fibrous plaques, whereas 122±21.64 and 152±23.35 in vulnerable plaques, respectively. No expression of BAX was found in controlled group. Conclusion The higher expression of Bax in vulnerable carotid plaque may be one mechanisms in molecular pathogenesis of carotid atherosclerosis which affect plaque stability and be the cause of higher incidence of stroke than fibrous carotid plaques, the regulation of BAX expression in different stage of atherosclerosis may provide targets in gene therapy for carotid atherosclerosis.     

Significance of ultrasound evaluation of carotid atherosclerotic plaque for diagnosing ischemic cerebrovascular disease

BACKGROUND: Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease. Therefore, the close relationship of carotid atherosclerotic plaque and ischemic cerebrovascular disease, and ultrasound evaluation of carotid atherosclerotic plaque have become the hot spot in studying ischemic cerebrovascular disease. OBJECTIVE: This study was to detect the degree of carotid atherosclerosis of ischemic cerebrovascular disease patients by ultrasonography, and to analyze the situation of carotid atherosclerosis and its relationship with clinic. DESIGN: Clinical randomized concurrent control experiment. SETTING: Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA. PARTICIPANTS: Totally 60 outpatients and inpatients with ischemic cerebrovascular disease, 42 males and 18 females, admitted to Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA between January 2006 and December 2006 were involved in the patient group. They met the diagnosis criteria of ischemic cerebrovascular disease constituted by the 4th Cerebrovascular Disease Conference in 1996, and were confirmed to suffer from ischemic cerebrovascular disease by skull CT and MRI. Another 20 subjects who received healthy examination concurrently in the same hospital, 12 males and 8 females, were involved in the control group. Informed consents of detected items were obtained from involved subjects. METHODS: The plaque thickness of mid portion, distal end and crotch of common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA) of involved subjects, who received health examination was separately detected with color Doppler ultrasonograph (HDI-5000). Then, total integral of plaque was calculated. The intima-media thickness (IMT) was measured with two-dimensional ultrasonography. The inner diameter stenosis degree of subjects who had plaque was measured. Blood flow parameters were recorded, and stenosis degree and plaque area were calculated. Blood flow volume of bilateral carotid artery and VA was separately measured with ultrasound equipment software, and brain blood flow volume was calculated. MAIN OUTCOME MEASURES: Atherosclerotic degree and blood flow volume of patients of two groups. RESULTS: Sixty patients with ischemic cerebrovascular disease and twenty subjects who received health examination participated in the final analysis. ①The IMT thickness, total plaque score, and total plaque area of patient group was significantly superior to that of control group, respectively（t=5.216–10.158，P < 0.05）. ② There were significant differences in the stenosis degree of CCA, ICA and VA between patient group and control group （t=6.720–12.816，P < 0.05）. ③ The blood flow volume of CCA, ICA, VA and brain of patient group was significantly lower than that of control group, respectively (t=2.872–10.860, P < 0.05). CONCLUSION: Ischemic cerebrovascular disease patients have different degrees of changes in atherosclerosis and arterial blood flow.     

中国汉族人群PARK16基因多态性与帕金森病易患性的关联

目的 探讨PARK16基因单核苷酸多态性(SNP)与帕金森病(PD)易患性的关系,分析其SNP的基因型和等位基因频率及不同基因型的优势比(OR)和其临床特征.方法 采用病例-对照研究选择PD患者226例和362名健康对照,利用TaqMan荧光定量PCR方法检测中国汉族人群中PARKl6基因Rs947211和Rs823128基因多态性,并对不同基因型临床资料进行分析.结果 PARKl6基因的多态性位点Rs947211在PD组基因型频率为∶GG 34.1%(77/226)、AG 46.0%(104/226)、AA 19.9%(45/226),对照组分别为23.8%(86/362)、53.0%(192/362)、23.2%(84/362),2组基因型频率差异具有统计学意义(以野生型GG为参考,AG∶OR=0.57,95%CI 0.38～0.85,P=0.006;AA∶OR=0.55.95%CI,0.34～0.85,P=0.015).以PD组野生型GG为参照,暴露于A等位基因型(AA+AG)的OR=0.56,95%CI0.38～0.82,P=0.003.晚发型PD(LOPD)Rs947211的基因型频率与对照组比较差异亦有统计学意义(AG∶OR=0.46,95%C/0.27～0.78,P=0.004∶AA∶OR=0.35,95%C/0.18～0.68,P=0.002).PD组3种基因型在临床表现上差异没有统计学意义.Rs823128在PD组基因型频率分布与对照组差异无统计学意义(以野生型AA为参照,AG∶OR=1.12,95%CI0.75～1.68,P=0.568;GG∶OR=0.99,95%CI0.35～2.76,P=0.994).结论 中国汉族人群中PARK16基因与PD易患性相关.

Abstract：

Objective To investigate the association between PARK16 gene polymorphism and Parkinson's disease(PD)susceptibility in Chinese Han population.and to analyze its single-nucleotide polymorphism(SNP)genotypes,frequencies and odds ratios(OR)of different genotypes.Methods The association between two SNP loci in PARK16 gene(Rs947211,Rs823128)and PD susceptibility was investigated by TaqMan quantitative polymerase chain reaction(PCR)in 226 PD patients and 362 healthy controls.Allele and genotype frequencies were calculated by the Chi-square test,and the clinical data were also analyzed.Results Three genotypes of Rs947211(GG,AG and AA)account for 34.1%(77/226),46.0%(104/226),19.9%(45/226)in the PD group,and 23.8%(86/362),53.0%(192/362),23.2%(84/362)in the control group,respectively.There was significant difference between two groups (P<0.05).Setting the GG genotype as the reference,OR values of AG and AA genotype were 0.57(95%CI0.38-0.85,P=0.006)and 0.55(95%CI 0.34-0.85,P=0.015),while the OR value for exposure to the A allele(AA+AG)was 0.56(95%CI0.38-0.82,P=0.003).Genotypes of Iate-onset PD were also significantly different from the controls(OR valne of AG=0.46,95%CI 0.27-0.78,P=0.004:OR value of AA=0.35.95%CI 0.18-0.68,P=0.002).And there was no diffefence in clinical features among the 3 genotypes. The frequency of Rs823128, another locus, in PD group was not significantly different from the control group( AA genotype as the reference, OR value of AG was 1. 12, 95% CI 0. 75-1.68, P = 0.568; OR value of GG was 0.99, 95% CI 0.35-2.76, P = 0.994). Conclusion Polymorphism of PARK 16 locus Rs947211 is associated with PD patients in Chinese Han population.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.