HIV-1耐药突变及突变型

目前已有25个治疗HIV-1的抗逆转录病毒药物(ARV)批准上市:9个核苷类逆转录酶抑制剂(NRTI),4个非核苷类逆转录酶抑制荆(NNRTI),9个蛋白酶抑制剂(PI),1个融合抑制剂,1个CCR5抑制剂,1个整合酶抑制剂.首个CCR5抑制剂和整合酶抑制剂于2007年批准,有的将融合抑制剂、CCR5抑制剂和整合酶抑制剂统称为侵入抑制剂(EI).     

HAART进展

自1996年高效抗反转录病毒治疗（HAART）问世以来,艾滋病（AJDS）的死亡率已经呈现明显下降趋势,其中美国的平均死亡人数就由1995年的5万人下降到了2002年的2万人。其死亡原因主要是HIV本身相关性疾病,占总死亡人数的40％,另外,肝脏疾病、治疗副反应、自杀行为和药物过量等也是病人死亡的重要原因。目前HAART的治疗方案主要由2种核苷类反转录酶抑制剂（NRTI）加上一种非核苷类反转录酶抑制剂（NNRTI）或一种强化蛋白酶抑制剂PI（加服利托那韦）组成。另外,3种NRIT组合也可作为备选方案之一,其主要优点是线粒体毒性较低（如3TC＋FTC＋tenofovir）,但临床证实治疗效果不如2NRTI/NNRTI或2NRTI／PI。现在的HAART一线药物追求更多的是服用方便而且毒性要低,比如阿扎那韦（atazanavir）,一种新型的PI,每天只需给药一次而且代谢毒性要比其它所有的PIs都低。随着越来越多HAART新药的相继问世,AIDS的治疗已经取得了巨大的进步,但仍存在许多亟待解决的问题,比如耐药性的出现等使得AIDS的攻克仍是一个巨大的难关。     

儿童人免疫缺陷病毒感染抗逆转录病毒治疗后外周血T淋巴细胞亚群的变化

目的 观察儿童人免疫缺陷病毒感染抗逆转录病毒治疗后外周血CD4^＋T细胞、CD4^＋／CD8^＋比值的变化，探讨这些变化的临床意义。方法 2002年-2006年对湖北省19例HIV／AIDS儿童进行抗逆转录病毒治疗，治疗方案为2种核苷类逆转录酶抑制剂（NRTIs）和1种非核苷类逆转录酶抑制剂（NNRTIs）的联合应用。治疗前（M0），治疗后第1-36个月（M1-36）定期检测外周血CD4^＋T、CD8^＋T细胞数量。结果 CD4＋T细胞数和CD4^＋／CD8^＋比值在治疗后M3显著增加（P〈0．05），其中，CD4^＋T细胞数绝对值在M12达到峰值，至M36均维持在较高水平，CD4／CD8比值在治疗后M9上升至峰值。结论 儿童HIV／AIDS抗逆转录病毒治疗后CD4^＋T细胞数、CD4^＋／CD8^＋比值显著增加，有助于机体免疫重建。     

艾滋病及其研究进展

（接上期）４ 艾滋病毒感染的治疗４．１ 抗逆转录病毒治疗的进展 抗逆转录病毒治疗始于１９８７年,当时研究提示一种核苷类逆转录酶抑制剂（ＢＴＩ）ＡＺＴ可以减少艾滋病人的发病和病死率。随后又有其它一些核苷类ＲＴＩ药物相继问世,９０年代初,抗病毒治疗主要使用单一核昔类ＲＴＩ药物,虽然改善了病人的临床状况,但是病毒耐药等问题很快也困扰了疗效的改进。因此,人们尝试把ＡＺＴ与及其它核苷类ＲＴＩ药物联合使用,并发现联合用药比单独使用ＡＺＴ有更好的效果,到１９９５年联合用药很快为发达国家临床广泛采用［８］。 １９９…     

阿波卡韦获准用于艾滋病鸡尾酒疗法

美国北卡罗来纳州葛兰素史克制药公司(GSK)近日宣布,该公司的最新药品Ziagen(硫酸阿波卡韦)获得美国食品和药品管理局(FDA)批准用于治疗艾滋病的鸡尾酒疗法,与其它抗逆转录病毒药物联合使用治疗艾滋病病毒感染。阿波卡韦是一种核苷逆转录酶抑制剂(NRTI),自1998年12月开始进入临床试用。美国FDA基于临床试验结果证实阿波卡韦与其它抗逆转录病毒药物的联合使用可为艾滋病的临床治疗带来新的希望。     

第十三届国际HIV耐药会议概况（续）

核苷逆转录酶抑制剂(NRTI).三联NRTI治疗方案.试验证实齐多夫定／拉米夫定／阿巴卡韦(abacavir)的三联治疗效果与efavirenz方案相比较差一些，并意外发现接受缺少齐多夫定的三联核苷逆转录酶抑制剂(NRTI)方案治疗的患者有很高的早期病毒失败率(机制不明)，因此三联NRTI方案不再作为HIV感染初始治疗的合适选择。     

去羟肌苷、司他夫定联合奈韦拉平治疗AIDS患者疗效观察

抗逆转录酶病毒治疗(ART)的目的是有效地抑制HIV病毒的复制和长期维持极低的病毒量.该法虽然无法彻底治愈艾滋病(AIDS),但已经成功降低AIDS患者的病死率.使用一种蛋白酶抑制剂(PI)和2种核苷类逆转录酶抑制剂(NRTI)联合治疗的传统方案,由于患者常难以耐受PI药物长期治疗的不良反应[1],常中断治疗而影响疗效.     

广西≥50岁男性新报告人类免疫缺陷病毒感染者的基因亚型及治疗前耐药分析

目的 分析广西≥50岁男性新报告人类免疫缺陷病毒(HIV)感染者的基因亚型及治疗前耐药情况。方法 采用分层随机抽样法，选取广西14个城市2020年1至6月新报告≥50岁男性HIV感染者，采用巢式逆转录聚合酶链反应扩增HIV-1 pol基因片段进行测序，分析耐药突变位点及耐药程度。结果 共615例HIV感染者纳入分析，CRF01＿AE、CRF07＿BC和CRF08＿BC 3种主要亚型的构成比分别为57.4%(353/615)、17.1%(105/615)和22.4%(138/615)。核苷逆转录酶抑制剂(NRTI)、非NRTI(NNRTI)和蛋白酶抑制剂发生耐药位点突变例数分别为8例(1.3%)、18例(2.9%)和0例。NRTI和NNRTI位点突变率最高的分别为M184V(0.7%)和K103N(1.8%)。22例(3.6%)至少对任意一类逆转录酶抑制剂产生耐药，其中，对NRTI耐药4例(0.7%)、NNRTI耐药14例(2.3%),同时产生耐药4例(0.7%);对蛋白酶抑制剂未产生耐药。NNRTI治疗前耐药率高于NRTI(2.9%比1.3%;χ²=3.929,P...     

结核菌与HIV重叠感染治疗决策

结核病是艾滋病患者最常见的机会性感染之一,约1/3艾滋病患者死于结核病。异烟肼、利福平、乙胺丁醇联合吡嗪酰胺是目前一线抗结核方案。2种核苷类逆转录酶抑制剂联合1种非核苷类逆转录酶抑制剂或蛋白酶抑制剂的高效抗逆转录病毒疗法(HAART)则是抗艾滋病的重要武器。     

HIV1感染成人和青少年抗逆转录病毒药物的使用（第四部分）

8经治病人的处理 推荐：①虽然大多数病人从采用抗逆转录病毒方案中获益，依从性，不能耐受毒性和药代动力学问题可使治疗复杂化，并且病毒学失败或治疗有限毒性常见。②抗逆转录病毒治疗失败的估价应包括评估病人的HIV疾病的严重性；抗逆转录病毒治疗史，包括持续时间，药物使用，抗逆转录病毒强度，依从性历史，和药物不能耐受，毒性，以及最近和先前药物耐药试验的结果。③治疗中病毒失败被定义为在24wk后HWRNA水平〉400拷贝／mL，48wk后〉50拷贝／mL或先前病毒血症抑制到〈400拷贝／mL后重复HIV RNA水甲〉400拷贝／mL。④在处理病毒学失败中，医生应区别有限，居中，和广泛先前治疗暴露和耐药。⑥对有限或居中先前药物暴露和药物耐药的治疗目标是建立最大病毒学抑制。⑥对有广泛先前药物暴露和药物耐受者，此时用现在可用药物要达到病毒抑制已有困难或不可能，治疗目标是保存免疫功能和预防临床进展。⑦对有广泛先前抗逆转录病毒治疗和经治失败有药物耐药的病人的评估和处理极为复杂，和专家咨询很重要。     

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.