Increased carotid intima–media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease

Aim: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima–media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.
Methods: The common carotid artery intima–media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women).
Results: The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706±211 µm and 749±395 µm, respectively) compared with that of the control population (614±113 µm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima–media thickening greater than 1.2 mm.
Conclusion: This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.     

牙周基础治疗对龈下菌斑中螺旋体及牙周状态影响的研究

目的：动态观测牙周基础治疗对龈下菌斑中螺旋体百分组成及牙周临床指标的影响。方法：对26例牙周病患者78个牙位的龈下菌斑用刚果红染色，计数螺旋体的百分比，记录牙周探诊深度，探诊出血指数和牙齿动度，分析治疗前后的变化。结果：龈上洁治及龈下刮治后1周，龈下菌斑中螺旋体百分比显著下降且牙周临床指数明显改善；刮治后2周，龈下菌斑中螺旋体百分比继续下降，但不具有显著性；刮治后3周，龈下菌斑中螺旋体百分比出现回升趋势。结论：牙周基础治疗是慢性牙周病有效治疗手段；牙周维护治疗对防止牙周再感染和牙周病的复发具有重要意义。     

COX基因多态性与缺血性卒中的相关性研究

【摘要】 目的 探讨环氧合酶(COX)代谢通路基因多态性及其与缺血性卒中发病率的关系。方法 将2013年2月~2015年11月在德阳市人民医院和温州医科大学第三附属医院神经内科住院经头颅CT和MRI检查确诊的299例急性缺血性卒中患者,根据彩超结果分为颈动脉易损斑块组（VP）94例、稳定斑块组（SP）74例和无斑块组（NP）131例;同时再分为颈动脉内膜增厚组（IT）108例和非内膜增厚组（NT）191例。使用聚合酶链反应和质谱分析测定基因多态性,包括前列腺素合酶1(PTGS1 rs1236913)、前列腺素H合酶2(PTGS2 rs689466)、血栓素A2合酶(TBXAS1 rs2267679、rs41708、rs194149)、前列腺素E合酶(PTGES2 rs6478818)、环前列腺素合成酶(PTGIS rs5602、rs5629)。结果 在易损斑块组和无斑块组之间TBXAS1 rs194149 GG基因型(P=00281),PTGIS rs5602 CT基因型(P=00319)存在显著差异。内膜增厚组和非内膜增厚组之间PTGS2 rs689466 GG基因型(P=00216)显示显著差异。多元回归分析显示,PTGIS的AA基因型(P=00308,OR:0275,95%CI:0079～0955)和PTGS2的AG+ GG基因型(P=00065,OR:2162,95%CI:1232～3795)是内膜增厚的破坏性因素。结论 COX的单核苷酸多态性(SNP)与脑梗死的发病率存在相关性,PTGIS和PTGS2基因多态性与内膜增厚脑卒中患者相关。     

心脑血脉宁对家兔动脉粥样硬化易损斑块模型MMP-2＼TIMP-2表达的影响

[目的】探讨心脑血脉宁对家兔动脉粥样硬化易损斑块模型基质金属蛋白酶一2（MMP-2）、基质金属蛋白酶抑制因子一2（TIMP一2）表达的影响。【方法】通过喂养高脂饲料和主动脉球囊内皮拉伤术复制动脉粥样硬化易损斑块模型,实验分为模型组,假手术组,心脑血脉宁组,历时15周。处死后,取腹主动脉行苏木精一伊红（HE）染色,观察镜下病变,计数斑块破裂数,免疫组化方法检测MMP一2、TIMP一2蛋白含量。【结果】1）HE观察：假手术组镜下形态结构完整,模型组斑块中心可见大量脂核,斑块表面覆盖纤维帽,在斑块肩部可见残存泡沫细胞和大炎细胞浸润。心脑血脉宁组介于两者之间。2）免疫组化结果：与假手术组相比,模型组MMP一2、TIMP一2蛋白含量明显升高,差异有显著性（P〈0．01）;心脑血脉宁组MMP一2与模型组比较表达降低,差异有显著性（P〈0．01）,而TIMP一2含量与模型组相比有降低趋势,但无统计学差异（P〉0．05）;心脑血脉宁组能够有效降低两者比值,与模型组相比差异有显著性（P〈0．01）。【结论】心脑血脉宁干预家兔动脉粥样硬化易损斑块模型,能减少斑块破裂,其机制可能与降低斑块MMP一2含量以及调节MMP一2与TIMP一2比值有关。     

活血胶囊对家兔动脉粥样硬化斑块稳定性的影响

目的 探讨活血胶囊对兔动脉粥样硬化斑块的作用及其稳定动脉粥样硬化斑块的机制.方法通过高脂饮食建立实验性动脉粥样硬化动物模型,采用生化分析测定血脂、酶联免疫吸附法(ELISA)测定血清白细胞介素-6(IL-6)水平及免疫组织化学染色法研究动脉粥样硬化斑块中CD68、肿瘤坏死因子-α(TNF-α)表达,光镜下观察动脉粥样硬化血管形态学及斑块病理变化.结果与模型组比较,活血胶囊可显著降低血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇( LDL-C)水平(P＜0.05);减少动脉粥样硬化斑块内巨噬细胞的浸润,降低斑块内TNF-α表达及血清IL-6的水平(P＜0.05),并呈现一定的量效关系.结论活血胶囊具有改善斑块稳定性的作用,该作用机制可能与其抑制动脉粥样硬化的炎症过程有关,其改善斑块稳定性方面与辛伐他汀有相似的作用.     

Development and validation in Ecuador of the EPD Questionnaire,a diabetes‐specific patient‐reported experience and outcome measure: A mixed‐methods study

IntroductionThe global prevalence of diabetes in 2019 in adults was estimated to be 9.3%. This study developed in Ecuador, for the first time, instruments to assess patient‐reported outcomes and experiences.MethodsThe Experiences of the Person with Diabetes (EPD) Questionnaire is a diabetes‐specific instrument. A mixed‐methods study was conducted. First, a qualitative item development phase that included four focus groups and six semi‐structured interviews with patients was conducted in different rural and urban areas of Ecuador to obtain information on culture, beliefs, demographics, diet and social perspectives. A second quantitative phase for psychometric validation was carried out in primary care settings of rural and urban areas of Ecuador.ResultsForty‐two and four hundred and eighty‐nine participants were included in each phase, respectively. The item development phase resulted in a questionnaire of 44 items (23 for perceived outcomes and 21 for experiences). In the validation study, most participants were women (58%) and from urban areas (57%). Exploratory factor analysis revealed three dimensions for each instrument. Outcomes instrument dimensions were symptoms and burnout, worries and fears and social limitations. Experiences instrument dimensions were information, patient‐centred care and care delivery. Cronbach''s α values of the total score and dimensions were high, ranging between .81 and .93 in both instruments. Confirmatory factor analysis showed an acceptable fit of the data.ConclusionThe EPD Questionnaire is probably the first instrument developed to assess patient‐reported experiences and perceived outcomes in a middle‐income country that included patients to capture all dimensions relevant for the intended population. Its psychometric properties are robust and could provide valuable information for clinicians and policymakers in the region.Patient or Public ContributionThe development of these instruments has taken into consideration patients and the public since their conception. A qualitative approach gathered relevant information related to the cultural, social and economic burden of different populations in Ecuador. Before validation, a pilot test was carried out with users of the National Health Services to obtain their perspectives and insights of the developed instrument. Finally, during the data analysis, we have given special consideration to social variables such as rural and urban populations.     

不同剂量阿托伐他汀对颈动脉粥样斑块的影响

目的研究不同剂量阿托伐他汀对颈动脉粥样硬化斑块的影响。方法应用彩色多谱勒超声检出颈动脉粥样硬化斑块形成者98例,随机分为A组（常规治疗对照组）、B组（常规治疗加口服阿托伐他汀10mg）和C组（常规治疗加口服阿托伐他汀20mg）,治疗6月后比较治疗前后血脂、颈动脉内膜中层厚度（IMT）及斑块大小的变化。结果A组、B组、C组治疗后IMT分别为（1．08±0．16）mm,（0．96±0．11）mm,（0．92±0．09）mm,C组治疗后IMT较A组、B组及治疗前有明显差异（P〈0．05）。C组总胆回醇（TC）和低密度脂蛋白胆目醇（LDL—C）治疗后较A组降低。斑块大小治疗前后以及和对照组比较差异无显著性。结论阿托伐他汀能延缓颈动脉粥样硬化斑块的进展,长期每天服用阿托伐他汀20mg比10mg疗效明显。     

血塞通软胶囊对颈动脉粥样硬化软斑块的影响

目的 观察血塞通软胶囊对颈动脉粥样硬化斑块中软斑块的临床疗效.方法 将240例患者按随机数字表法分成两组各120例.对照组采用肠溶阿匹林、辛伐他汀常规治疗;治疗组在对照组治疗基础上加用血塞通软胶囊,两组均治疗6个月为1个疗程,随访1年.结果 两组治疗后软斑性质、数目、体秘均较治疗前显著改善,且治疗组在软斑消退、软斑转为硬斑、软斑数目、软斑体积等方面优于对照组(t=3.525,P＜0.01).治疗组心脑血管事件发生和再住院情况优于对照组(t=3.678,P＜0.01).结论 血塞通软胶囊可有效治疗颈动脉粥样硬化软斑块,降低心脑血管疾病事件的发生率.     

Tolerability,pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody,in Chinese healthy volunteers and psoriatic patients

Aim:

To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and primary tolerability of an anti-CD11a monoclonal antibody (CMAB001) in Chinese healthy volunteers and psoriatic patients.

Methods:

Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0 or 2.0 mg/kg. The other was a multiple-dose study: 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks.

Results:

CMAB001 was well tolerated in the single- and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMAB001 reached its highest level 2 d later after the injection, and the C_max increased in an approximate dose-proportionate manner, while the area under curve (AUC) showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection.

Conclusion:

CMAB001 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.     

补肾抗衰片对实验性动脉粥样硬化家兔的NF-κB及炎症因子的影响

目的 探讨补肾抗衰片对家兔动脉粥样硬化的干预作用及作用机制。