肝病患者手术及介入治疗后凝血纤溶指标监测对疗效的评估作用

目的探讨肝病患者手术或介入治疗后凝血及纤溶指标的变化对疗效的评估价值。方法对肝病组（100例）、肝癌组（100例）于手术或介入治疗前与后检测血浆凝血酶原时间（PT）、活化部分凝血酶原时间（AFTT）、纤维蛋白原（FIB）、抗凝血酶Ⅲ（ATⅢ）活性、蛋白C（PC）活性、蛋白S（PS）活性、纤溶酶原（PLG）活性、组织型纤溶酶原活化物（t-PA）、纤溶酶原活化剂抑制物（PAI）、α2-抗纤溶酶（α-PI）活性、纤溶酶-纤溶酶抑制物（PAP）,并与正常对照组100例比较。结果与对照组比较,肝癌组介入治疗前与后PT、APT、t-PA、PAI、PAP均明显升高（P〈0．05或〈0．01）,FIB、ATⅢ活性、PC活性、PS活性、PLG活性、α2-PI活性均明显降低（P〈0．05或〈0．01）;与介入治疗前比较,介入治疗后PT、APTT、t-PA降低,FIB、ATⅢ活性、PC活性、PS活性、PLG活性、α2-PI活性升高（P〈0．05）,而PAI-1和PAP均差异无统计学意义（P〉0．05）。与对照组比较,肝病组手术治疗前与后PT、APTT、t-PA、PAP均明显升高（P〈0．05或〈0．01）,而FIB、ATⅢ、PC活性、PS活性、PLG活性、PAI、α2-PI活性降低（P〈0．01）;与手术治疗前比较,肝病组手术治疗后PT、APTT、t-PA、PAP降低（P〈0．05或〈0．01）,FIB、ATⅢ活性、PC活性、PS活性、PLG活性、PAI、α2-PI活性升高（P〈0．05或〈0．01）。结论肝病组和肝癌组均存在抗凝活性降低及易发纤溶。手术或介入治疗后有所改善,但未完全恢复正常。     

纤溶系统变化对心房颤动的临床评价

目的研究心房颤动（房颤）的纤溶系统改变及其临床意义。方法采用发色底物法测定30例房颤患者和25例正常人血浆组织型纤溶酶原激活剂（t-PA：a）活性和纤溶酶原激活剂抑制物（PAl：a）活性;并测定纤雏蛋白原（Fg）浓度、凝血酶原时间（PT）和部分凝血活酶时间（APTT）。结果房颤患者与正常人相比,血浆t-PA：a降低（P〈0．01）;PAl：a升高（P〈0．01）;PM：a／t-PA：a比值增高（P〈0.01）,而Fg、PT、APTT无统计学意义（P〉0．05）。风湿性心脏病房颤与冠心病房颤之间血浆t-PA：a,PAI：a,PAI：a／t-PA;a比值及PT、APTT均无统计学意义（P〉0．05）,但前组血浆№浓度较后组低（P〈0．05）。结论房颤患者血浆存在低纤溶状态,表现为PAI活性增加,t-PA活性降低,房颠的低纤溶状态可能与其高发血栓栓塞并发症有关。     

联合应用小剂量尿激酶及低分子肝素治疗不稳定性心绞痛的临床研究

目的：探讨联合应用小剂量尿激酶及低分子肝素治疗不稳定性心绞痛的临床效果。方法：对确诊的不稳定性心绞痛（除外变异性心绞痛）100例患，采用单盲随机分为两组，对照组50例，给予硝酸甘油阿司匹林、β受体阻滞及钙离子拮抗剂等常规治疗；治疗组50例在上述治疗基础上加用尿激酶10万－30万单位静点，每日一次，连用10日，同时每日尿激酶静点完毕，给予低分子肝素0.4ml腹部皮下注射，每日一次，连用10日，结果：对照组显效13例（26．0％）、有效13例（26．0％），总有效率52．0％，治疗组显效30例（60．0％），有效17例（34．0％）。总有效率94．0％，两组疗效对比有效显差异（P＜0．01）。观察随访1个月，在心脏事件（死亡＋急性心肌梗死例数）发生率上，治疗组6．0％，对照组20．0％，明显低于对照组（P＜0．05）。两组治疗前后监测血小板计数，出凝血时间，凝血酶原时间，激活的部分凝血活酶时间，其对比无显差异（P＞0．05）。结论：联合应用小剂量，延长疗程的尿激酶溶栓及低分子肝素凝治疗UAP安全，有效。     

缬沙坦和苯那普利对慢性房颤患者纤溶系统影响的比较

目的：比较血管紧张素Ⅱ1型（AT1）受体拮抗剂和血管紧张素转换酶抑制剂（ACEI）对房颤患者纤溶系统的作用。方法：采用随机，双盲，交叉设计，选入30例慢性房颤患者分为三组，缬沙坦治疗组（口服80mg/天），苯那普利治疗组（口服10mg/天），对照组：三组均不限使用抗心力衰竭药物。治疗前及治疗第10天各采静脉血1次，测定组织型纤溶酶原激活物（t-PA）活性和组织型纤溶酶原激活抑制物1型（PAI－1）活性t-PA抗原含量，PAI－1抗原含量。结果：三组的t-PA活性，t-PA抗原含量治疗前后自身比较均有差异（P＜0．05），各组PAI－1活性，PAI－1抗原含量治疗前后也有显著差异（P＜0．05），但对照组无明显性差异（P＞0．05）。缬沙坦组和对照组相比较，t-PA活性，PAI－1活性和PAI－1抗原含量P＜0．01，t-PA抗原含量P＜0．05。苯那普利组和对照组比较，tPA活性无显著性差异（P＞0．05），t-PA抗原含量，PAI－1活性和PAI－1抗原含量均有差异（P＜0．05）。缬沙坦和苯那普利组比较，t-PA活性，PAI－1活性，PAI-1的含量有显著性差异（P＜0．05），t-PA抗原含量无差异（P＞0．05）。结论：AT1受体拮抗剂和PAI－1活性，PAI－1抗原含量有显著性差异（P＜0．05），t-PA抗原含量无差异（P＞0．05）。结论：AT1受体拮抗剂和PAI－1活性，PAI－1抗原含量有显著性差异（P＜0．05），t-PA抗原含量无差异（P＞0．05）。结论：AT1受体拮抗剂和PAI－1活性，PAI－1抗原含量显著性差异（P＜0．05），t-PA抗原含量无差异（P＞0．05）。结论：AT1受体拮抗剂和ACE抑制剂通过减轻内皮系统的损伤，对慢性房颤患者的纤溶系统有改善作用，并且AT1受体拮抗剂优于ACE抑制剂。     

D—二聚体与不同类型老年冠心病及纤溶活性的相关性

目的 探讨D－二聚体（DD）、纤维蛋白原（Fg)、凝血酶原时间（PT）、部分凝血活酶时间（KPTT）在不同类型老年冠心病中的变化及相互关系。方法 分别对80例老年冠心病患者和50例老年健康人的DD，Fg含量进行了检测，并测定其PT，KPTT。结果 急性心梗（AMI）组和不稳定性心绞痛（UA）组的DD，Fg含量明显高于对照组、稳定性心绞痛（SA）组和陈旧性心梗（OMI）组（P＜0．01）；AMI组与A 比较差异有显著性（P＜0．05）；冠心病合并高血压、糖尿病组DD，Fg含量高于无合并症组（P＜0．01）。AMI组PT，KPTT比其它各组明显缩短（P＜0．01）。结论 冠心病患者体内血浆DD，Fg含量与病变程度有关，提示冠心病患者体内存在着高凝状态和继发性纤溶活性增强。     

急性心肌梗死血小板及纤溶活性改变

目的：了解急性心肌梗死（AMI）患血小板活化及纤溶状态在发病机制中的作用。方法：测定27例AMI患及正常组对照血浆GMP－140、T-PA:A、PAI：A、D－D。结果：AMI患血浆GMP－140、PAI：A含量明显高于正常对照组（P＜0．01），而t-PA:A含量则明显低于正常对照组（P＜0．01）。恢复期血浆GMP－140低急性期（P＜0．05）。D－D在急性期内（≤2天）无显增高，恢复期高于急性期及正常对照组（P＜0．01）。结论：AMI患血小板活性增高而纤溶性降低，要积极施行抗血小板治疗和早期溶栓治疗，并重视动脉粥样硬化的防治，减少血管内皮细胞损害，预防心肌梗死的发生。     

小剂量尿激酶联合低分子肝素防治伴高凝状态妇科肿瘤患者术后深静脉血栓形成的临床效果

【摘要】 目的 观察小剂量尿激酶联合低分子肝素防治伴高凝状态妇科肿瘤患者术后深静脉血栓（DVT）形成的临床效果。方法 按照入院顺序将140例行手术治疗的伴高凝状态妇科肿瘤病例进行编号,将其分为观察组（单号）与对照组（双号）各70例,对照组只给予低分子肝素治疗,观察组给予小剂量尿激酶联合低分子肝素治疗,比较两组术后1h、术后7d凝血系统分子［纤维蛋白原（Fbg）、D 二聚体（D D）、血管性假性血友病因子（vWF）、抗凝血酶复合物（TAT）、抗凝血酶（AT）］水平、凝血酶原时间（PT）与部分凝血活酶时间（APTT）、血小板聚集率、下肢周径值及血流速度、并发症情况、DVT发生率。结果 术后7d,观察组Fbg、D D、vWF、TAT水平、血小板聚集率明显低于对照组(P＜005),AT明显高于对照组(P＜005);观察组PT、APTT明显长于对照组(P＜005),下肢周径值与血流速度均明显优于对照组(P＜005);观察组术后并发症总发生率为143%、DVT发生率为000%显著低于对照组的1000%和571%(P＜005)。结论 伴高凝状态的妇科肿瘤患者术后接受小剂量尿激酶联合低分子肝素治疗,能显著改善其凝血功能,有效抑制血小板大量聚集,优化下肢血流状态,降低DVT风险,且并发症少。     

补阳还五汤联合小剂量尿激酶治疗时间窗外脑梗死疗效分析

目的：探讨补阳还五汤联合小剂量尿激酶治疗时间窗外急性脑梗死的临床疗效。方法：将135例急性脑梗死患者随机分为补阳还五汤联合小剂量尿激酶治疗组（A组,48例）,小剂量尿激酶组（B组,46例）和常规治疗组（C组,41例）。观察3组疗效和治疗前后神经功能缺损程度评分（NIHSS）、D-二聚体（D—D）、凝血因子指标（纤维蛋白原-Fg、凝血酶原时间-PT、活化部分凝血活酶时间-APTT、国际标准化比值-INR）的变化。结果：A组治疗总有效率为91．67％,明显高于B组的86．36％和c组的75．61％．P〈0．05。治疗后14d,A组的NIHSS评分、D—D和Fg显著低于B组和C组,P〈0．05;A组和B组PT、APTT、INR明显高于c组,P〈0．05。结论：补阳还五汤联合小剂量尿激酶治疗溶栓时间窗外急性脑梗死安全、有效。     

不稳定心绞痛血小板CD63，CD62P表达及血浆PAI—1，C—RP含量的变化及药物的干预作用

目的：探讨血小板表面活性蛋白血小板颗粒膜蛋白（CD63,溶酶体膜蛋白（CD62P）,血浆纤溶酶原激活抑制物（PAI－1）及C－反应蛋白（C－RP）在不稳定心绞痛（UAP）发生及发展中的作用,及葛根素对不稳定心绞痛患者CD63,CD62P,PAI－1及C－RP的影响,方法：59例UAP患者随机分成葛根组32例及氯塞匹定组27例,比照观测治疗4周前后血小板CD63,CD62P及血浆PAI－1,C－RP水平的变化。结果：与健康及稳定性心绞痛（SAP）对照组比较,UAP患者血小板CD63,CD62P及血浆PAI－1,C－RP水平明显升高（P＜0．05或P＜0．01）;随着不稳定心绞痛Braunwald分级的加重,血小板CD63,CD62P及血浆PAI－1,C－RP水平亦增加;治疗6周后,葛根素组及氯塞匹[定组CD63,CD62P,PAI－1及C－RP测定值分别显著低于治疗前水平（P＜0．05,或P＜0．01）;而治疗后两组间上述各指标水平无统计学差异（P＞0．05）,结论：血小板活化及纤溶机制异常及炎症反应物这三者在UAP发生及发展过程中起着重要的作用,葛根素及氯塞匹定抗血小板活性,改善纤溶活性及减轻炎症反应的突出作用及预防急性冠状动脉综合征的发生和发展有极其重要的临床意义。     

不稳定型心绞痛患者冠脉循环中凝血纤溶的变化

目的:了解不稳定型心绞痛(UAP)患者冠脉循环中凝血纤溶的变化.方法: 选22例UAP患者和10例经冠脉造影证实冠状动脉无狭窄的患者为研究对象.采集冠状静脉窦(CS)、主动脉根部(AO)和上腔静脉(SVC)血,测定组织型纤溶酶原激活剂(t-PA)和纤溶酶原激活剂抑制剂(PAI)活性、D-二聚体(DD)及纤维蛋白原(Fg)含量.结果:与对照组相比,UAP患者冠脉循环中t-PA活性减低(P＜0.05),PAI活性增高(P＜0.01),Fg含量增高(P＜0.01),DD含量增高但无统计学意义(P＞0.05).UAP患者三部位各指标测定结果无明显差异(P＞0.05).结论:UAP患者存在凝血、纤溶功能的失调,UAP患者纤溶活性降低,凝血功能增强;UAP患者在心绞痛缓解后,冠脉循环中凝血、纤溶状态与周围循环血中一致.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.