红花黄色素联合前列地尔治疗Buerger病40例疗效观察

目的探讨红花黄色素联合前列地尔治疗Buerger病的临床疗效。方法Buerger病患者80例，随机分为治疗组和对照组各40例，均行卧床休息、戒烟、足部运动锻炼、扩容、抗凝、前列地尔静滴等综合治疗；在此基础上治疗组另加红花黄色素静滴，1次／d，14d为1个疗程；观察两组临床疗效及胭动脉血流速度变化。结果治疗组总有效率为87．5％，对照组为60．0％，治疗组临床疗效优于对照组（P〈0．01）。治疗后治疗组胭动脉血流速度为（43．6±4．3）cm／s，对照组为（41．3±4．5）cm／s，治疗组胭动脉血流较对照组明显改善（P〈0．05）。结论红花黄色素联合前列地尔治疗Buerger病安全、有效。     

循环压力泵治疗下肢动脉粥样硬化闭塞实验兔的疗效

目的探讨循环压力泵改善下肢动脉粥样硬化闭塞症(ASO)的疗效。方法将具有ASO的24只实验兔,随机分为A组和B组,每组12只,A组用循环压力泵对右下肢进行泵血,B组为循环压力泵未对右下肢股动脉进行泵血。穿刺股动脉,收取所需血液行生化检查。在压力泵最大转速(150 r/min)的转速下,收取血液行生化检查。以转速50 r/min,启动压力泵,持续给实验兔泵血1 h,术后再次抽出所需血液行生化检查,测量右下肢远端股动脉平均容积流量与平均血流速度;测量右下肢远端皮温;测量实验兔右下肢末端氧饱和度。结果 1体外泵血前后K+、血常规、血沉指标差异无统计学意义(P0.05)。2A组体内泵血前后电解质、肝功能、肾功能各项指标差异无统计学意义(P0.05);B组体内泵血前后电解质、肝功能、肾功能各项指标差异无统计学意义(P0.05)。3A、B两组体内泵血后平均容积流量与平均血流速度、右下肢远端温度差异、右下肢远端温度差异有统计学意义(P0.05)。结论 1在最大转速时,循环压力泵对血液生化无影响;2在一定的转速的范围内,循环压力泵对ASO兔股动脉泵血,未造成缺血再灌注损伤;3循环压力泵是一种有效的改善ASO兔下肢动脉血液供应的方法。     

彩色多普勒超声对早、中晚期肝硬化的肱股动脉血流动力学的分析

研究肝硬化病人外周动脉血流参数变化,采用彩色多普勒超声检测了３０例早期肝硬化病人,３４例中晚期肝硬化病 及２０例正常人的肱、股动脉血流参数。结果显示：中晚期肝硬化的肱、,股动脉收缩期峰值流速（ＰＳＶ）,平均瞬时不充速（ＴＡＭｎ）,血流量（Ｑ）〉明显低于对照组,肱股动脉血管直径（Ｄ）阻力指数（ＲＩ）和搏动指数（ＰＩ）早期、中晚期肝硬化组与正常组比较无差异。肝硬化后会导致我周动脉血流动力学参数改变,这     

奥扎格雷纳联合低分子肝素钙治疗糖尿病下肢动脉疾病的临床效果

目的分析探讨奥扎格雷钠联合低分子肝素钙治疗糖尿病下肢动脉疾病的临床效果,对其治疗特点进行总结。方法选择2013年4月—2014年5月该院收治的糖尿病下肢动脉疾病患者作为研究对象,共90例,按照数字抽签法,将这90例患者分成两组,一组为实验组共46例,一组为对照组共44例,对照组患者采取低分子肝素钙进行临床治疗,实验组患者采取奥扎格雷钠联合低分子肝素钙进行临床治疗,并在治疗结束后,对比分析两组患者的治疗总有效率、不良反应率及治疗前后的腘动脉收缩期峰值血流速度。结果实验组患者治疗后的左右腘动脉收缩期峰值血流速度分别为(59.73±23.14)cm/s、(57.95±24.61)cm/s,对照组患者治疗后的左右腘动脉的收缩期峰值血流速度分别为(54.66±24.11)cm/s、(51.16±23.22)cm/s,差异有统计学意义(P0.05);实验组患者治疗后的显效例数为26例,无效例数为3例,对照组患者治疗后的显效例数为16例,无效例数为10例,差异有统计学意义(P0.05);实验组患者的不良反应例数少于对照组患者,差异有统计学意义(P0.05)。结论奥扎格雷钠联合低分子肝素钙可以有效改善糖尿病下肢动脉疾病患者的临床症状,提高其治疗有效率,减少不良反应率,进一步促进患者恢复健康,故值得在临床实践过程中大力借鉴和推广。     

增强型体外反搏对冠心病患者外周循环即时血流动力学影响的临床观察研究

目的观察冠状动脉粥样硬化性心脏病(冠心病)患者在增强型体外反搏(EECP)的作用下,其对外周循环(颈总动脉、肱动脉)血流动力学的即时影响。方法连续入选2018年8月至2018年12月于中山大学附属第八医院(深圳福田)心内科门诊及住院的冠心病患者(n=97),所有患者均进行1次45 min体外反搏治疗,在体外反搏治疗前、中、后使用超声多普勒评价颈总动脉和肱动脉血流动力学参数的变化特性,包括收缩期峰值流速(PSV)、舒张期峰值流速(PDV)、舒张末期流速(EDV)、时间-平均峰值流速(TAMAX)、搏动指数(PI)、阻力指数(RI)和血流量(FR)。结果颈总动脉血流量在反搏过程中升高(P0.01),反搏后仍有上升趋势,而肱动脉血流量在反搏前、反搏中及反搏后差异无显著性(P0.05)。在反搏过程中,PI、RI及PDV均升高(P0.05),而EDV显著降低(P0.01),反搏后均恢复至反搏前水平。PSV、TAMAX在反搏前、反搏中及反搏后差异无显著性(P0.05)。结论 EECP能有效增加颈总动脉及肱动脉舒张期血流速度,并增加颈动脉平均血流量,提示EECP干预对冠心病患者外周循环的血流动力学有积极的影响。     

纤溶酶对椎-基底动脉供血不足血流动力学的影响

目的探讨纤溶酶对椎-基底动脉供血不足(VBI)血流动力学影响及其疗效。方法65例病人随机分为观察组(33例)和对照组(32例),对照组使用倍他西汀(西其汀),观察组在对照组基础上加用纤溶酶100U加入生理盐水250mL静脉输注。统计分析治疗1周后两组在临床症状、血浆纤维蛋白原及椎-基底动脉血流动力学等方面变化情况,评估其疗效。结果观察组在改善临床症状、降低血浆纤维蛋白原及加快椎动脉(VA)、基底动脉(BA)收缩期血流速度等方面与对照组比较有统计学意义(P<0.05或P<0.01)。治疗后观察组和对照组总有效率分别为100.0%和87.5%(P<0.05)。结论加用纤溶酶治疗VBI可降低血浆纤维蛋白原,改善椎-基底动脉供血,提高疗效。     

肝硬化门静脉高压患者脾动脉盗血的临床价值

目的:探讨肝硬化门静脉高压与肝动脉、脾动脉血流动力学关系,为肝硬化门静脉高压患者的诊断及治疗提供依据.方法:利用彩色多普勒超声检测46例肝硬化门静脉高压患者与88例健康对照组肝动脉、脾动脉、脾静脉及门静脉血流动力学变化.结果:门静脉高压组脾动脉、脾静脉及门静脉血流指标均高于对照组(P0.05),肝动脉血流量较对照组减少,差异有统计学意义(P0.05).结论:肝硬化门静脉高压患者脾动脉明显增粗、迂曲,脾动脉血流量增加,而肝动脉细小,血流量减少,肝硬化门静脉高压患者脾动脉盗血现象普遍存在.     

应用彩色多普勒超声对糖尿病足病人下肢动脉血管病变的研究

目的观察糖尿病足（DF）病人下肢动脉形态学和血流动力学的改变。方法正常受试者（NS）25例，糖尿病（DM）病人26例，非肢端坏疽糖尿病足病人（NGDF）30例和肢端坏疽糖尿病足（GDF）病人26例。应用Acusonl28xP／10彩色电脑声像仪，线阵探头，频率7．0MHz，观察下肢动脉管径和血流的变化。结果DF两组病人下肢动脉血管病变，主要从胴动脉部位开始动脉硬化，尤其以胫后和足背动脉最为显著，动脉狭窄和闭塞是肢端缺血、坏疽的主要病因。观察发现，DM病人已有下肢胭动脉血流速度增高的血流动力学改变，GDF组病人胫后和足背动脉血流速度明显低于其他各组。结论彩色多普勒超声检测能帮助临床对糖尿病足下肢血管病变严重程度的判断、糖尿病足的诊断和治疗方案的制定有实用价值。     

糖尿病患者肾内动脉血流参数变化的临床意义

目的　探讨糖尿病患者肾内动脉血流参数变化的临床意义。方法　将 64例糖尿病肾病患者按 2 4小时尿白蛋白排泄率 ( UAE)分为三组 ,采用美国 Acuson-As Pen彩色多谱勒能量图 ( CDEI) ,检测其肾内动脉血流分布情况及相关参数。结果　 1组 ( 3 0例 ;UAE<10 ug/ min,运动后升高 )段间动脉收缩期峰值血流速度( Vm ax)、舒张末期血流速度 ( Vmi)、阻力指数 ( RI)与正常对照组 ( 3 0例健康人 )比较 ,均无显著性差异( P>0 .0 5) ;2组 ( 2 5例 ,UAE15～ 2 0 ug/ min)和 3组 ( 9例 ,UAE>2 0 0 ug/ min)以上各参数均明显高于对照组 ( P<0 .0 1) ,随肾损害程度的加重 ,肾彩色血流显像逐渐减少 ,阻力指数 ( RI)及脉动指数 ( PI)增高。结论　肾动脉血流参数为判断糖尿病肾病血管损害程度的主要依据     

高血压早期肾损害肾内血流动力学异常临床分析

目的对高血压合并早期肾损害患者的肾内动脉血流动力学异常状况进行分析。方法随机选择我院200例原发性高血压患者为观察组,按照既定的标准将其划分无早期肾损害患者100例和早期肾损害患者100例,另外选择100名身体健康的志愿者作为对照组。利用彩超多普勒技术对MRA(主肾动脉)、SRA(叶段动脉)、IRA(叶间动脉)的Vs(收缩期峰速度)、Vd(舒张期末速度)、Vm(平均血流速度)、AT(血流峰速加速时间)、PI(脉冲指数)以及RI(阻力指数)等血流参数进行测定,取两肾的平均值为最总结果。结果观察组患者的MRA(主肾动脉)、SRA(叶段动脉)、IRA(叶间动脉)的Vs(收缩期峰速度)、Vd(舒张期末速度)、Vm(平均血流速度)均较对照组低(P0.05);PI(脉冲指数)以及RI(阻力指数)较对照组明显增高(P0.05),AT(血流峰速加速时间)无明显差距(P0.05);早期肾损害组和无早期肾损害组的组内比较结果为SRA(叶段动脉)、IRA(叶间动脉)的Vs(收缩期峰速度)、Vd(舒张期末速度)、Vm(平均血流速度)降低,AT(血流峰速加速时间)延长,PI(脉冲指数)以及RI(阻力指数)增高(P均0.05),差异具有统计学意义。结论原发性高血压患者在早期肾损害阶段肾内血流动力学处于异常状态。     

Usefulness of waveform analysis of popliteal artery in Type II diabetic patients using gated magnetic resonance 2D-cine-PC imaging and 31P spectroscopy

Abstract Aims/hypothesis. We studied 76 patients with Type II (non-insulin-dependent) diabetes mellitus and 16 age-matched non-diabetic subjects (control group) to clarify qualitative and quantitative abnormalities of waveform and flow volume of the popliteal artery. Methods. The 76 diabetic patients comprised 16 patients with occlusive arterial disease in the lower extremities [arteriosclerosis obliterans (ASO) group] and 60 patients free from this disease (non-ASO group). We flow analysed the popliteal artery and measured the phosphocreatine to inorganic phosphate ratio of resting plantar muscles to identify risk factors for foot lesions using gated magnetic resonance two-dimensional cine-mode phase-contrast imaging and ³¹P spectroscopy. Results. The control and non-ASO groups had a triphasic waveform with systolic, early and late diastolic components. All ASO patients had an abnormal monophasic waveform and a lower ankle brachial index than that of the control and non-ASO groups. To clarify the mechanism of reduced flow volume of lower extremities, we assigned the 60 patients of the non-ASO group to the three subgroups based on their levels of total flow volume of the popliteal artery. The lowest group showed an abnormal triphasic waveform with lower amplitudes of systolic and late diastolic components and flow velocities in foot arteries than those of the highest group although ABI was similar. From stepwise multiple regression analysis, late diastolic flow volume was identified as an independent determinant for the phosphocreatine to inorganic phosphate ratio (r ² = 0.484, p < 0.001). Conclusion/interpretation. Waveform analysis of popliteal artery provides a powerful tool for identifying impaired peripheral circulation caused by either occlusive arterial disease or increased arterial resistance in diabetic patients. [Diabetologia (2000) 43: 1031–1038] Received: 24 January 2000 and in revised form: 31 March 2000     

老年周围动脉闭塞性疾病内皮和非内皮依赖性舒张功能的无创研究

目的　探讨老年周围动脉闭塞性疾病 (peripheralarterialocclusivedisease,PAOD)内皮依赖性舒张功能 ,即血流介导的血管扩张功能 (flow mediateddilation ,FMD)和硝酸甘油介导的非内皮依赖性舒张功能 (nitroglycerin mediateddi lation,NMD)状况及其相关因素。方法　采用超声多普勒检测 33例已确诊为PAOD的老年患者肱动脉FMD及NMD ,并分别与 40例健康老年人及 30例具有心血管危险因素的老年非PAOD患者进行对照研究。结果　老年PAOD患者FMD及NMD均显著低于对照组 ;肱动脉基础内径、收缩压、低密度脂蛋白胆固醇与FMD呈负相关 ;FMD与NMD呈正相关 ,肱动脉基础内径与NMD呈负相关。结论　老年PAOD患者FMD及NMD均受损 ;肱动脉基础内径、收缩压、低密度脂蛋白胆固醇可能是FMD独立的预测因子 ;而FMD及肱动脉基础内径与NMD密切相关。     

老年人椎动脉谐波显像及血流动力学变化特征

目的研究组织谐波显像技术对老年人椎动脉的显示能力及老年人椎动脉血流动力学变化。方法对145例健康自愿者的290条椎动脉分别进行组织谐波显像检查和基波显像检查。比较组织谐波显像和基波显像对椎动脉的显示能力;比较老年组(≥60岁)与对照组(<60岁)椎动脉内径、峰值血流速度、椎动脉血流量和阻力指数。结果谐波显像可提高椎动脉的显示率;谐波显像对椎动脉第1、2、3段的显示率分别为94.4%、100%和95.5%,老年人椎动脉第1、3段的显示率低于对照组;老年人椎动脉血流峰值流速、血流量小于对照组,阻力指数高于对照组。结论老年人椎动脉的显示率低于青、中年,组织谐波显像可以显著提高椎动脉的显示率,多普勒超声能够反映老年人椎动脉血流变化特征。     

Pulsed Doppler assessment of deep femoral artery hemodynamics: a preliminary report

The functional capability of the deep femoral artery (DFA) as a collateral channel is an important feature in patients suffering peripheral arterial occlusive disease (PAOD). A noninvasive method of indirect quantification of the DFA blood flow volume is presented. In normal lower limbs, it was found that the common femoral artery (CFA) mean blood flow volume was maintained at 59% of its resting value when the superficial femoral artery (SFA) was occluded by a pneumatic cuff placed around the thigh. The reduction of the mean flow volume is mainly due to an increase of the diastolic backward flow, while the maximum systolic flow remains constant. In a few patients with various degrees of stenosis of the DFA, we observed a much greater drop in mean CFA blood flow volume than in normal subjects. On the basis of this preliminary study, we conclude that: --When the normal SFA is occluded, pulsatile flow through the CFA is maintained. --Occlusion flow reflects the runoff and the compliance of the DFA bed. --Occlusion flow is diminished in patients with DFA stenosis. It is suggested that this non-invasive test might help the physician to assess the involvement of the DFA in PAOD. Further investigation is needed to establish the correlation between quantitative occlusion blood flow volume and the degree of DFA stenosis.     

气压治疗频次对老年髋关节置换术后下肢血流速度和肿痛的影响

目的观察多频次气压治疗对全髋关节置换术后下肢静脉血流速度与肿痛的影响。方法选取2018年10月-2020年1月复旦大学附属闵行医院骨科收治的人工全髋关节置换术后患者80例,分为观察组和对照组,每组各40例,2组患者均接受术后常规康复治疗,观察组气压治疗:30 min/次,2次/日,每次间隔时间约3 h;对照组气压治疗:30 min/次,1次/日。2组分别于治疗前、治疗后第3天和治疗后第7天进行疼痛和肿胀程度评估,并采用多普勒超声波对下肢股总静脉、股深静脉和腘静脉血流速度进行检测。结果术前2组患者患侧下肢血流速度变化、周径和VAS(疼痛)评分比较差异无统计学意义(P>0.05),治疗后第3天:2组VAS评分和患肢周径、患肢股总静脉、股深静脉和腘静脉血流速度变化比较差异有统计学意义(P<0.05);治疗后第7天:VAS评分和患肢周径、患肢股总、股深和腘静脉血流速度变化比较差异无统计学意义(P>0.05)。结论髋关节置换术后采用常规康复治疗结合3 d内多频次气压治疗,在深静脉血栓预防和肿痛改善上优于单次治疗。在肿痛减轻后,单次气压治疗即可。     

Left Atrial Systolic Performance in the Presence of Elevated Left Ventricular End-Diastolic Pressure: Evaluation by Transesophageal Pulsed Doppler Echocardiography of Left Ventricular Inflow and Pulmonary Venous Flow Velocities

We recorded left ventricular inflow (LVIF) and pulmonary venous flow (PVF) velocities by transesophageal pulsed Doppler echocardiography in 25 patients with a ratio of peak atrial systolic to early diastolic LVIF velocity of <1 and a left ventricular end-diastolic pressure (LVEDP) of 15 mmHg or greater, as well as in 30 normal subjects. The group consisted of 14 patients with prior myocardial infarction, 7 with dilated cardiomyopathy, and 4 with cardiac amyloidosis, and were divided into: (1) group A (n = 7): peak atrial systolic LVIF velocity of 40 cm/sec or greater; (2) group B (n = 7): peak atrial systolic LVIF velocity of <40 cm/sec and peak atrial systolic PVF velocity of 30 cm/sec or greater; and (3) group C (n = 11): peak atrial systolic LVIF velocity of <40 cm/sec and peak atrial systolic PVF velocity of <30 cm/sec. Although LVEDPs in groups B and C were significantly greater than in group A, there was no difference between groups B and C. The mean pulmonary capillary wedge pressure (mPCWP) in group C was significantly greater than in groups A and B, but there was no difference between groups A and B. The difference between LVEDP and mPCWP (LVEDP - mPCWP) in group B was significantly higher than in groups A and C. Dilatation of the left atrium (LA) was seen in all three groups, particularly in groups B and C. There were no differences in peak atrial systolic LVIF velocity and LA volume change during atrial contraction between group A and the control group, and there were no differences in LA volume change and peak second systolic PVF velocity between groups A and B. LA volume change and peak second systolic PVF velocity were significantly less in group C than in groups A and B. Among the four patients whose courses could be observed after medical treatment with diuretic and vasodilator, one changed from group B to A, one from group B to C, one from group C to A, and one remained in group C. Thus, recording of peak atrial systolic LVIF and PVF by transesophageal pulsed Doppler echocardiography permits detailed evaluation of LA systolic performance in the presence of elevated LVEDP. These two variables provide important information for less invasive differentiation of LA afterload mismatch from LA myocardial failure.     

Evaluation of coronary flow reserve in hypertensive patients by dipyridamole transesophageal doppler echocardiography

This study evaluates the coronary flow reserve (CFR) in hypertensive patients with and without left ventricular (LV) hypertrophy. CFR was assessed by transesophageal Doppler echocardiography in 15 normal subjects (group I), 21 hypertensive patients without LV hypertrophy (group II), and 27 hypertensive patients with LV hypertrophy (group III). All hypertensive patients were complaining of typical anginal pain and had normal coronary angiograms. The sample volume was placed at the bifurcation of the left main and left anterior descending coronary arteries. Coronary blood flow velocities were evaluated at rest, 2 minutes after dipyridamole infusion, and 2 minutes after intravenous aminophylline. The ratios of dipyridamole to rest peak diastolic and systolic velocities were considered as indexes of CFR. Peak diastolic velocity ratio was significantly lower in group III than in groups I and II (1.6 +/- 0.2, 2.7 +/- 0.4, and 2.1 +/- 0.2, respectively; p <0.05), and it was significantly lower in group II than I (p <0.05). The peak systolic velocity ratio was significantly lower in group III than in groups I and II (1.7 +/- 0.3, 2.8 +/- 0.3, and 2.1 +/- 0.2, respectively; p <0.05), and it was significantly lower in group II than I (p <0.05). The peak diastolic velocity ratio was inversely related to systolic blood pressure, diastolic blood pressure, and LV mass index (r = -0.48, -0. 51, and -0.37 respectively) in hypertensive patients. It is concluded that CFR is significantly impaired in hypertensive patients, especially those with LV hypertrophy, compared with healthy subjects. The degree of impairment of CFR is related to LV mass index.     

椎动脉型颈椎病的彩色多普勒超声检测

为探讨超声检测颈椎病合并椎动脉供血不足的价值 ,运用彩色多普勒超声观察了 5 0例椎动脉型颈椎病患者椎动脉的形态结构 ,检测其血流速度、阻力指数、搏动指数和血流量。将测得的各参数进行统计学处理 ,结果发现 ,与对照组相比 ,颈椎病组椎动脉的阻力指数和搏动指数明显增高 (P <0 .0 5 ) ,而峰值流速、舒张末期流速和血流量轻微下降 (P >0 .0 5 ) ,但差异无显著性。以上提示 ,彩色多普勒超声为椎动脉型颈椎病提供了椎动脉形态学及血流动力学改变的依据。     

Flow analysis of left internal thoracic artery in myocardial revascularization surgery using y graft

In order to evaluate the left internal thoracic artery flow pattern, when the vessel is used as a graft to supply the left coronary artery system, we evaluated flow by Doppler measurement, both at rest and under dobutamine stress. There were 2 groups of 20 patients each: group A patients received only a left internal thoracic artery graft to the left anterior descending artery, and group B patients received a pedicled left internal thoracic artery graft associated with a vein graft, which together supplied the left anterior descending artery and another branch of the left coronary artery. Angiography showed patent grafts in all patients from both groups. The following characteristics were evaluated: systolic flow, diastolic flow, total flow, total flow under stress/total flow at rest ratio, systolic peak velocity, diastolic peak velocity, and systolic peak velocity/diastolic peak velocity ratio. In group A, the total flow was 45.5 +/- 21.6 mL/min at rest and 68.3 +/- 32.9 mL/min under stress. In group B, the total flow was 98.2 +/- 50.4 mL/min at rest and 175.7 +/- 79.2 mL/min under stress. Comparison between groups showed a total flow increase in group B of 115.8% (P=0.0002) at rest and 157.2% (P <0.0001) under stress. The other characteristics were also statistically significant, except systolic flow, total flow under stress/total flow at rest ratio, and systolic peak velocity. Our results showed that the left internal thoracic artery sufficiently supplies regional myocardium at rest and during exercise (stress), demonstrating its great adaptability in response to demand.     

Acute cigarette smoking-induced hemodynamic alterations in the common carotid artery--a transcranial Doppler study--.

BACKGROUND: Cigarette smoking has been shown to temporarily alter cerebral flow velocity and vasomotor reactivity, so the aim of this study was to assess the acute effects of smoking a single cigarette on the common carotid artery (CCA) hemodynamics in healthy nonsmokers. METHOD AND RESULTS: Using a 7.0 MHz linear transducer of a computed sonography system, the CCA hemodynamics, including the diameter of the left and right CCA, peak systolic velocity, maximum end-diastolic velocity, time-averaged maximum velocity pulsatility index, resistivity index, flow volume, diameter and area of the CCAs, were measured in 16 healthy nonsmokers before and immediately after smoking a cigarette. Compared with the baseline, heart rate and blood pressure significantly increased, the diameter, flow volume and area of each CCA were unchanged, and the pulsatility index and resistivity index were significantly altered after smoking. In addition, the peak systolic velocity, maximum end-diastolic velocity and time-averaged maximum velocity were significantly altered after smoking. CONCLUSIONS: Cigarette smoking significantly altered the CCA hemodynamics in nonsmokers, probably as a consequence of enhanced adrenergic activity.