血清钙、尿酸检测在子痫前期中的意义

目的探讨血清钙及尿酸水平与子痫前期的关系。方法选取轻度子痫前期孕妇49例,重度子痫前期孕妇62例,正常妊娠者65例,分别测定其血清钙、尿酸水平并作比较。结果轻度子痫前期组、重度子痫前期组及正常对照组孕妇血清钙水平分别为(2.16±0.11)mmol/L、(2.03±0.14)mmol/L及(2.16±0.11)mmol/L,轻度子痫前期组、重度子痫前期组孕妇血清钙水平均低于正常对照组,差异有统计学意义(P<0.05),重度子痫组低于轻度子痫组(P<0.05);轻度子痫前期组、重度子痫前期组及正常对照组孕妇血清尿酸水平分别为(326.36±60.57)mol/L、(381.98±78.21)mol/L及(263.80±63.79)mol/L,轻度子痫前期组及重度子痫前期组孕妇血清尿酸水平均高于正常对照组(P<0.05),重度子痫前期组孕妇血清尿酸水平高于轻度子痫前期组(P<0.05)。结论孕妇血清钙、尿酸水平与子痫前期严重程度密切相关,可作为子痫前期诊断及预测指标,对子痫前期的早发现、早治疗具有重要意义。     

血清铁蛋白与子痫前期的关系研究

目的 探讨血清铁蛋白与子痫前期发病及病情严重程度的关系.方法 回顾性分析2018年11月至2019年10月空军军医大学第二附属医院进行产检的459例孕妇资料,根据是否发生子痫前期分为子痫前期组和对照组,再以妊娠期糖尿病(GDM)为分层因素分为GDM+子痫前期组、单纯子痫前期组、GDM组和正常组,比较各组孕早、中、晚期血清铁蛋白水平.结果 子痫前期组和对照组孕早、中、晚期血清铁蛋白水平比较,差异无统计学意义(P>0.05).而GDM+子痫前期组孕中期[(32.3±5.7)μg/L vs.(22.6±1.2)μg/L]、孕晚期[(41.6±7.8)μg/L vs.(24.9±1.0)μg/L]血清铁蛋白水平明显高于正常组,差异有统计学意义(P<0.05).结论 血清铁蛋白升高预示子痫前期的加重,但其并不是子痫前期的病因.     

子痫前期与妊娠期糖尿病血清尿酸变化及意义

目的:探讨子痫前期及妊娠期糖尿病(GDM)孕妇血尿酸水平的变化及其临床应用价值。方法:选择妊娠晚期轻度子痫前期孕妇42例(轻度子痫前期组),重度子痫前期孕妇40例(重度子痫前期组),妊娠期糖尿病孕妇36例(妊娠期糖尿病组),正常妊娠晚期妇女80例(对照组)作为研究对象,对各组血清尿酸进行测定。结果:轻度子痫前期组血清尿酸含量为198.7～414.3μmol/L,重度子痫前期组血清尿酸含量为247.8～745.2μmol/L,妊娠期糖尿病患者的血清尿酸含量为243.6～524.6μmol/L,各组与对照组比较,差异有显著性(P<0.05,P<0.01)。尿酸升高组围产儿预后不良的发生率比尿酸正常组高(P<0.05)。结论:子痫前期及妊娠期糖尿病患者血清尿酸水平明显高于正常晚孕妇女,血尿酸升高与围产儿预后密切相关,可作为子痫前期、妊娠期糖尿病预后的判断指标之一。     

重度子痫前期患者外周血中性粒细胞表面黏附分子LFA-1水平变化的研究

目的通过检测重度子痫前期孕妇及正常孕妇外周血中性粒细胞计数及中性粒细胞表面黏附分子淋巴细胞功能相关抗原1(LFA-1)的表达水平,探讨中性粒细胞活化与子痫前期发病的关系。方法选择2013年11月至2014年2月于中国医科大学附属盛京医院产科就诊的孕产妇28例,分为重度子痫前期组(n=14)和对照组(同期正常妊娠妇女,n=14)。2组孕产妇年龄、孕周无统计学差异。采用流式细胞术检测2组孕产妇外周血中性粒细胞表面黏附分子LFA-1的表达情况。检测重度子痫前期组患者平均动脉压,对其与中性粒细胞表面LFA-1表达水平进行相关性分析。结果重度子痫前期组外周血中性粒细胞计数[(8.40±2.23)×109/L]明显高于正常妊娠组[(6.71±1.58)×109/L],差异有统计学意义(P<0.05)。重度子痫前期组外周血中性粒细胞表面黏附分子LFA-1表达阳性率[(63.25±38.025)%]明显高于正常妊娠组[(38.32±38.65)%],差异有统计学意义(P<0.05)。重度子痫前期患者外周血中性粒细胞表面LFA-1表达水平与平均动脉压呈显著正相关(r=0.64,P=0.013)。结论重度子痫前期患者外周血中性粒细胞计数及其表面黏附分子LFA-1表达均较正常妊娠妇女明显升高,且与病情严重程度显著相关,提示中性粒细胞的活化参与了子痫前期发病。     

血清IL-18和IL-33联合PTX-3对子痫前期孕妇妊娠结局的预测价值

目的 分析血清白介素-18(IL-18)、IL-33联合正五聚蛋白-3(PTX-3)水平,探究其在子痫前期孕妇妊娠结局的预测价值。方法 选取2021年2月-2023年4月于沧州市人民医院就诊的子痫前期孕妇110例为子痫组,同时选取同期产检正常的60名孕妇作为正常组。比较正常组与子痫组血清IL-18、IL-33、PTX-3水平以及不良妊娠结局;子痫组根据妊娠结局分为良好妊娠组(n=71)与不良妊娠组(n=39),比较两组临床资料和IL-18、IL-33、PTX-3水平,分析影响子痫前期孕妇妊娠结局的因素及其对不良妊娠结局的预测价值。结果 子痫组IL-18(49.83±5.08)ng/L、PTX-3(2.77±0.31)μg/L水平高于正常组(45.08±4.55)ng/L、(1.31±0.15)μg/L,IL-33(21.44±2.46)ng/L低于正常组(29.69±3.13)ng/L,差异均有统计学意义(t=6.040、34.322、18.939,P均<0.05)。子痫组发生不良妊娠结局的发病率为35.45%,高于正常组8.33%,差异有统计学意义(χ²=...     

血清抵抗素水平与子痫前期的关系

目的:观察子痫前期患者血清抵抗素水平的变化,探讨抵抗素与子痫前期发生的关系.方法:应用双抗体酶联免疫吸附法(ELISA),检测正常非妊娠妇女(正常非孕组,28例)、早孕妇女(早孕组,27例)、中孕妇女(中孕组,26例)、晚孕妇女(晚孕组,26例)以及子痫前期患者(子痫前期组,25例)血清抵抗素的浓度.结果:①早孕组(6.660±0.546)μg/L、中孕组(5.058±0.461)μg/L与正常非孕组(5.450±0.418)μg/L血清抵抗素浓度无显著性差异(P>0.05);晚孕组血清抵抗素(8.659±0.698)μg/L显著高于正常组、早孕组以及中孕组(P分别<0.01,0.001和0.001).②子痫前期组抵抗素水平(5.162±0.484)μg/L低于晚孕组,差异有显著性(P<0.001),但与正常组、早孕组以及中孕组相比差异无显著性(P均>0.05).结论:血清抵抗素水平降低是子痫前期的重要变化,可能与子痫前期的病情有关.     

子痫前期孕妇血浆内皮素和心钠素水平变化及其临床意义

目的通过检测正常妊娠期孕妇及子痫前期孕妇血浆内皮素和心钠素的水平,探讨心钠素和内皮素在子痫前期发病过程中的作用。方法回顾性分析2010年5月~2013年12月北京军区总医院(以下简称"我院")收治的36例子痫前期妊娠妇女的临床资料,根据病情将其分为轻度组(20例)和重度组(16例),随机选择我院同期正常妊娠妇女30例为对照组。比较三组妊娠妇女入院时的血浆内皮素和心钠素水平,并采用ROC曲线对该诊断试验进行评价。结果重度组妊娠妇女内皮素和心钠素[(52.4±6.1)、(95.8±6.6)ng/L]高于轻度组[(45.3±5.1)、(88.7±5.8)ng/L]及对照组[(29.3±4.5)、(81.7±5.1)ng/L],且组间两两比较,差异均有统计学意义(P<0.05);重度组收缩压、舒张压、终止妊娠时间分别为(168±16)mm Hg(1 mm Hg=0.133 kPa)、(114±6)mm Hg、(29.5±1.2)周,轻度组分别为(154±14)mm Hg、(105±6)mm Hg、(35.8±1.5)周,对照组分别为(134±8)mm Hg、(79±8)mm Hg、(38.5±1.5)周,组间两两比较差异均有统计学意义(P<0.05);子痫前期轻度组、重度组的发病孕龄分别为(32.2±1.5)、(26.5±1.8)周,两组比较差异有统计学意义(P<0.05)。子痫前期轻度组和新生儿及胎儿总死亡率(23.75%)明显低于重度组(72.50%),差异有高度统计学意义(P<0.01);两组胎儿宫内生长迟缓率比较差异有高度统计学意义(P<0.01);内皮素ROC曲线下面积(AUC)=0.894>0.7,心钠素的ROC曲线AUC=0.899>0.7,说明采用内皮素和心钠素对早期子痫前期具有较高的诊断价值。结论内皮素和心钠素的水平与子痫前期的病情严重程度密切相关。     

血清叶酸、维生素B12、同型半胱氨酸水平在孕妇子痫前期中的表达及相关性

摘要：目的 分析妊娠妇女血清叶酸、维生素B12、同型半胱氨酸水平在孕妇子痫前期中的表达及相关性。方法 选取2016年7月至2018年7月在我院接受治疗与进行分娩的68例子痫前期孕妇作为研究对象,根据病情的轻重情况分为重度组（重度子痫前期,28例）,轻度组（轻度子痫前期,40例）,将同期在我院进行产检与正常分娩且一般资料与子痫前期孕妇均衡可比的50例健康孕妇作为健康组进行对照。对比三组产妇血清中叶酸、维生素B12、同型半胱氨酸（Homocysteine,Hcy）水平情况的差异,采用Spearman检验评估孕妇子痫前期血清中叶酸、维生素B12、Hcy水平与病情程度的相关性。结果 重度组叶酸、维生素B12水平显著低于轻度组与健康组,Hcy水平显著高于轻度组与健康组;轻度组叶酸、维生素B12水平显著低于健康组,Hcy水平显著高于健康组,差异均具有统计学意义（P＜0.05）;子痫前期不同病情严重程度患者在叶酸水平、Hcy水平差异有统计学意义（X2=9.112,4.089;P＜0.05）,在维生素B12水平差异无统计学意义（X2=0.899,P＜0.05）;Spearman相关性分析提示子痫前期孕妇血清中叶酸水平与子痫前期病情严重程度呈负相关（r=-0.613,P<0.001）,维生素B12水平与子痫前期严重程度不具有相关性（r=-0.236,P=0.076）,Hcy水平与子痫前期严重程度呈正相关（r=0.602,P=0.001）。结论 子痫前期孕妇血液中叶酸含量较低,且病情越严重叶酸表达水平越低,应加强对孕妇孕期叶酸的检测及监控。     

子痫前期患者妊娠早晚期血清胎盘蛋白13变化的研究

目的探讨胎盘蛋白13（PP13）在子痫前期患者妊娠早晚期血清中的变化及其意义。方法应用酶联免疫吸附试验（ELISA）对169例孕前血压正常的孕妇,在妊娠9～11周、32—34周2个时间段对母体血清中的PP13水平进行测定,观察孕妇孕期病情变化并随访妊娠结局。结果①169例孕妇发展为子痫前期21例,其中8例重度子痫前期、13例轻度子痫前期;148例妊娠结局正常。②169例孕妇血清PP13水平随着妊娠的进展,进行自身配对比较均逐渐上升,妊娠早晚期之间比较,差异有显著性意义（P〈0．01）。③在妊娠9～11周,轻度子痫前期组、重度子痫前期组血清PP13水平均显著低于对照组（P〈0．01）;在妊娠32～34周,轻度子痫前期组、重度子痫前期组血清PP13水平稍高于对照组,但轻度子痫前期组PP13与对照组比较,差异有统计学意义（P〈0．05）,而重度子痫前期组PP13与对照组比较,差异无统计学意义（P〉0．05）。结论子痫前期患者妊娠早期即有血清PP13水平异常表达,可能参与了子痫前期的发生与发展。     

PAPP-A及VEGF在子痫前期患者血清中的表达及其相关性研究

目的 观察子痫前期患者血清中妊娠相关血浆蛋白A (PAPP-A)及血清血管内皮生长因子(VEGF)表达情况,探讨其与子痫前期病情严重程度的关系.方法 选择2013年1月至2014年12月在上海市浦东医院门诊行常规产前检查并分娩的子痫前期孕妇60例为子痫前期组,根据病情严重程度将其分为轻度子痫前期组30例,重度子痫前期组30例.选取同期行本院门诊产前检查并住院分娩的正常孕妇30例为对照组.分别采用酶联免疫吸附试验测定三组孕妇血清中的PAPP-A水平和VEGF的水平,分析其与子痫前期患者病情严重程度的关系.结果 重度子痫前期组新生儿出生体重[(3.4±0.5) kg]低于轻度子痫前期组[(3.6±1.4) kg]和对照组[(3.7±0.5) kg],差异均具有统计学意义(P<0.05);重度子痫前期组患者血清PAPP-A值、VEGF值和24 h尿蛋白值分别为(900.6 ± 379.0) μg/ml、(7.2±4.2) pg/ml、(2.5±1.2) g/24 h,轻度子痫前期组分别为(783.8±204.7) μg/ml、(5.3±1.4) pg/ml、(1.4±0.3) g/24 h,均分别高于对照组的(592.9±222.9) μg/ml、(4.8±2.8) pg/ml、(0.2±0.1) g/24 h,差异均具有统计学意义(P<0.05);重度子痫前期组的血清PAPP-A值和24 h尿蛋白值均高于轻度子痫组,差异具有统计学意义(P<0.05);Speraman相关分析显示,血清PAPP-A值和血清VEGF值呈明显的正相关(r=0.574,P<0.05).结论 PAPPA及VEGF均参与了子痫前期的发生及发展.     

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.     

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.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.