血管旁路与动静脉转流治疗下肢动脉硬化闭塞症的疗效比较

目的评价血管旁路及动静脉转流术在治疗下肢动脉硬化闭塞症中的疗效。方法1998-01～2004-01对该病患者109例119条下肢，采用2种术式：①血管旁路：在股-胭动脉、胭-胫腓干动脉之间建立血管旁路；②动静脉转流：在股浅动脉-股浅静脉、胭动脉-胫腓干静脉之间建立动静脉转流，进行治疗观察。结果119条下肢随访4个月至5年，平均3年左右。血管旁路组79条下肢疗效满意或病情改善，1条截肢。动静脉转流组39条下肢疗效满意或病情改善，无截肢。结论血管旁路及动静脉转流在救治下肢动脉硬化闭塞症方面各有其优缺点，故应严格选择病例，掌握手术技巧，增加患肢救治率。     

髂动脉支架联合人工血管转流术治疗下肢动脉硬化闭塞症的效果

目的探讨髂动脉支架联合人工血管转流术治疗下肢动脉硬化闭塞症的效果,以供临床参考。方法选择2010年5月至2012年4月我院下肢动脉硬化闭塞症患者42例作为研究对象,均接受髂动脉支架联合人工血管转流术治疗,观察治疗效果和手术并发症,对比治疗前后踝/肱指数(ABI)的差异性。结果术后患者达到显效22例,有效18例,无效2例,总有效率为95.24%。术后发生感染2例,术肢肿胀5例,手术并发症发生率为16.67%。经对症处理后均痊愈。与治疗前比较,患者治疗后ABI明显上升,差异具有统计学意义(P<0.05)。结论采用髂动脉支架联合人工血管转流术治疗下肢动脉硬化闭塞症疗效满意,值得在临床工作中推广应用。     

人造血管架桥术治疗下肢动脉硬化闭塞症97例分析

目的探讨应用人造血管旁路移植术治疗下肢动脉硬化闭塞症的临床疗效。方法对两院2004年12月～2007年6月97例下肢动脉硬化闭塞症病人行人造血管旁路移植手术进行回顾性分析。主要术式为：单纯人造血管股-腘动脉膝上旁路术72例,股-腘动脉膝下旁路术12例,股-胫后动脉旁路术3例,股-胫前动脉旁路术1例;股-胫前、胫后动脉人造血管、自体静脉复合转流术9例。结果97例患者术后2周死亡3例（3/97）,围手术期死亡率3%,其余术后下肢缺血改善良好,踝/肱指数（ABI）有不同程度改善,升高幅度为0.19～0.45,平均升高0.33,术后随访9个月～33个月,平均18个月,移植血管阻塞16例（16/94）,总通畅率为83%。结论采用人造血管旁路移植术是治疗下肢动脉硬化闭塞症的有效方法。     

176例分期动静脉转流术的远期疗效

目的探讨分期动静脉转流术治疗血栓闭塞性脉管炎穴TAO雪和动脉硬化闭塞症的远期效果。方法回顾性分析本院16年间176例分期动静脉转流术的基本情况。结果147例获得随访,随访率83.5%。6例上肢和84例下肢低位深组转流患者,86例术后1周疼痛消失,4例术后仍有疼痛、跛行,良好率95.5%,不满意率4.5%,肢体保留率100%;57例下肢高位深组转流,术后5例截肢,截肢率8.8%,肢体保留率91.2%,43例疼痛于术后2～3周消失,良好率75.4%,9例术后仍有疼痛、跛行,但无静息痛,不满意率15.7%。结论分期动静脉转流术治疗TAO和肢体广泛性动脉硬化闭塞症临床效果满意,但应严格掌握手术适应证。     

低频脉冲磁疗治疗老年人下肢动脉硬化闭塞症的临床观察

目的：探讨低频脉冲磁疗治疗老年人下肢动脉硬化闭塞症的疗效。方法82例老年人下肢动脉硬化闭塞症患者进行随机分组。其中治疗组50例采用常规治疗同时合用低频脉冲磁疗，对照组32例采用常规治疗。比较两组的治疗效果。结果治疗组治疗10 d后临床疗效及6个月后下肢动脉血管超声狭窄率变化优于对照组，两组比较差异有统计学意义（P〈0.05）。结论低频脉冲磁疗治疗老年人下肢动脉硬化闭塞症具有良好疗效。     

下肢动脉硬化闭塞症多阶段复杂病变的杂交手术治疗

目的：探讨杂交手术治疗在下肢动脉硬化闭塞症多节段复杂病变中的临床疗效。方法回顾性分析13例下肢动脉硬化闭塞症采用杂交手术治疗的临床资料。结果13例患者均获治疗成功,未出现严重并发症,踝肱指数（ABI）复查由0.27上升至0.63（正常值0.53～0.91）,术后于1年进行彩色多普勒超声检查,通畅率100%。结论杂交手术治疗多节段复杂下肢动脉硬化闭塞症,具有安全、创伤小、术后通畅率高等优点,值得在临床上推广。     

腋-股动脉旁路转流术治疗主髂动脉硬化闭塞症

目的探讨腋-股动脉人造血管转流治疗主髂动脉硬化闭塞症的疗效。方法24例主髂动脉硬化闭塞症患者（30条患肢）,采用腋（同侧）-单股动脉或者腋双股动脉人造血管转流术治疗。结果1例术后并发败血症而截肢,23例手术成功,缺血症状缓解,有效率达96．7％;随访1年,通畅率达73.3％;7例（8条）人造血管闭塞的患者,5例（6条）经过人造血管取栓手术,血供恢复,2例截肢。结论腋-股动脉人造血管转流术,对于高龄、体弱或其他不适于作解剖旁路转流的主髂动脉硬化闭塞症患者,是一种保存肢体的较安全、有效的治疗方法。     

下肢股-腘动脉人工血管转流术手术配合23例体会

目的：报道股-腘动脉人工血管转流术的术中配合及体会。方法23例患者进行有效的心理护理,总结术前的充分准备及术中的护理配合要点。结果23例下肢动脉硬化闭塞症患者进行人工血管转流术均获成功,无严重并发症发生。结论充分的术前准备、积极的术中配合,可以提高手术的效率、手术质量。     

下肢动脉硬化闭塞症介入治疗术后并发症的观察与护理

目的：探讨下肢动脉硬化闭塞症介入术后并发症的观察重点及措施。方法：对138例下肢动脉硬化闭塞症患者,将血管成形、内支架置入、血栓及斑块旋切、溶栓、血栓抽出等介入治疗术后出现的并发症进行分类、分析,针对性实施护理。结果：本组138例患者有32例出现术后并发症,其中穿刺部位巨大血肿9例、下肢过度灌注综合征2例、假性动脉瘤3例、消化道出血3例、支架内急性闭塞4例、支架再狭窄10例,造影剂迟发型变态反应1例,占手术的23.2%。结论：下肢动脉硬化闭塞症介入治疗并发症发生率较高,认真细致的观察护理,及早发现问题,及时地采取有效的措施对疾病的预后非常关键。     

股动脉、腘动脉硬化闭塞症腔内的微创治疗分析

目的：探讨下肢动脉硬化闭塞症腔内治疗的效果。方法采用腔内球囊扩张及支架置入术治疗47例患者（共53支血管）的下肢血管硬化闭塞段。结果经血管腔内介入治疗后,复查造影证实病变段血管血流明显改善,技术成功率92.5%,无血管夹层及血栓形成等并发症,术后随访平均12个月疗效较好。结论血管腔内治疗下肢动脉硬化闭塞症安全、有效和微创的治疗方法。     

Pro-inflammatory cytokine inhibition in the primate using microencapsulated antisense oligomers to NF-kappaB

PRIMARY OBJECTIVE: Antisense oligomers to NF-kappaB (ASO) were incorporated into albumin microspheres to determine if microcapsules containing ASO inhibit pro-inflammatory cytokines to a greater extent than comparable doses of ASO in solution. Phagocytosis of microcapsules and intracellular release of ASO in macrophages was evaluated. RESEARCH DESIGN: Comparable doses of microencapsulated ASO and ASO in solution were evaluated in non-human primates. METHODS: Blood was sampled and stimulated with Escherichia coli endotoxin ex vivo. TNF, IL-1 and IL-6 concentrations were compared for 72 hrs. The intracellular concentration of ASO was measured in macrophages in vitro to evaluate the difference in intracellular penetration of microencapsulated ASO. RESULTS: Microencapsulated ASO produced significantly greater cytokine inhibition at all time points compared to ASO in solution. There were no side effects to ASO in the baboons. Intracellular ASO concentration was 10 fold greater in macrophages using microencapsulation. CONCLUSIONS: Microencapsulated ASO to NF-kappaB is more effective than ASO in solution in pro-inflammatory cytokine inhibition in non-human primates.     

抗链球菌DNA酶B抗体检测的临床应用价值

目的：通过同时检测患者血清中抗链球菌DNA酶B抗体（ADNase B）和抗链球菌溶血素O抗体（ASO）的含量,探讨ADNase B检测的临床应用价值。方法采用速率散射比浊法同时检测患者血清中ADNase B和ASO的含量。结果在2375名疑似风湿性疾病的患者中,405名ADNase B超出参考范围上限,占17.1%;220名ASO超出参考范围上限,占9.2%;513名ADNase B和（或）ASO超出参考范围上限,占21.6%;112名ADNase B和ASO均超出参考范围上限,占4.7%。结论ADNase B的阳性检出率高于ASO;二者联合检测能够进一步提高链球菌感染的检出率。     

Pro-inflammatory cytokine inhibition in the primate using microencapsulated antisense oligomers to NF-κB

Primary objective: Antisense oligomers to NF-κB (ASO) were incorporated into albumin microspheres to determine if microcapsules containing ASO inhibit pro-inflammatory cytokines to a greater extent than comparable doses of ASO in solution. Phagocytosis of microcapsules and intracellular release of ASO in macrophages was evaluated.

Research design: Comparable doses of microencapsulated ASO and ASO in solution were evaluated in non-human primates.

Methods: Blood was sampled and stimulated with Escherichia coli endotoxin ex vivo. TNF, IL-1 and IL-6 concentrations were compared for 72?hrs. The intracellular concentration of ASO was measured in macrophages in vitro to evaluate the difference in intracellular penetration of microencapsulated ASO.

Results: Microencapsulated ASO produced significantly greater cytokine inhibition at all time points compared to ASO in solution. There were no side effects to ASO in the baboons. Intracellular ASO concentration was 10 fold greater in macrophages using microencapsulation.

Conclusions: Microencapsulated ASO to NF-κB is more effective than ASO in solution in pro-inflammatory cytokine inhibition in non-human primates.     

前列地尔注射液治疗下肢动脉硬化闭塞症的临床研究

目的：以前列地尔注射液（商品名：凯时,北京泰德制药有限公司生产）为阳性对照药物,评价上海福达制药有限公司生产的前列地尔注射液治疗下肢动脉硬化闭塞症的疗效与安全性。方法：全国8家医院采用随机、双盲、阳性药平行对照研究,观察试验组（前列地尔,114例）、对照组（凯时,110例）在综合疗效、间歇性跛行、静息痛、踝肱指数值的改善以及不良事件发生情况。结果：试验组总有效率为87.50%,对照组为85.45%。两组不良事件的发生率、严重程度以及与药物的相关性之间的比较,差异均无统计学意义（P〉0.05）。结论：前列地尔与凯时治疗下肢动脉硬化症的有效性与安全性无差异。     

Antisense oligonucleotides: from design to therapeutic application

1. An antisense oligonucleotide (ASO) is a short strand of deoxyribonucleotide analogue that hybridizes with the complementary mRNA in a sequence-specific manner via Watson-Crick base pairing. Formation of the ASO-mRNA heteroduplex either triggers RNase H activity, leading to mRNA degradation, induces translational arrest by steric hindrance of ribosomal activity, interferes with mRNA maturation by inhibiting splicing or destabilizes pre-mRNA in the nucleus, resulting in downregulation of target protein expression. 2. The ASO is not only a useful experimental tool in protein target identification and validation, but also a highly selective therapeutic strategy for diseases with dysregulated protein expression. 3. In the present review, we discuss various theoretical approaches to rational design of ASO, chemical modifications of ASO, ASO delivery systems and ASO-related toxicology. Finally, we survey ASO drugs in various current clinical studies.     

闭塞性周围动脉粥样硬化患者血管内皮损伤的研究

目的:观察闭塞性周围动脉粥样硬化(ASO)患者的凝血和纤溶系统功能的变化,探讨ASO患者的内皮损伤机制。方法:选择ASO患者82例(患者组)和健康对照80例(对照组),采用流式细胞仪测定循环内皮细胞(CEC)和内皮祖细胞(EPCs)数量。采用酶联免疫吸附法测定凝血酶-抗凝血酶复合物(TAT)。采用血液凝固仪测定凝血因子Ⅶ活性(FⅦ:A)、纤维蛋白原(FIB)、vW因子抗原水平(vWF∶Ag)、组织型纤溶酶原激活物活性(t-PA∶A)及纤溶酶原活化抑制物活性(PAI∶A)水平。以vWF∶Ag参考范围上限(150%)作为医学决定水平,将患者组分为vWF∶Ag正常组(38例)和vWF∶Ag增高组(44例)。结果:患者组PAI∶A、FⅦ∶A、FIB、vWF∶Ag、TAT和CEC高于对照组,EPCs低于对照组,vWF∶Ag增高组的PAI∶A、FⅦ∶A和TAT均高于vWF∶Ag正常组,差异有统计学意义(均P<0.01);患者组vWF∶Ag与FⅦ∶A、PAI∶A、TAT均呈正相关(P<0.01)。结论:ASO患者存在较严重的血管内皮损伤,内皮细胞大量脱落,且损伤后的修复能力不足,其纤溶和凝血系统功能紊乱和血管内皮损伤程度相关。     

An update on the pharmaceutical management of thrombosis

Introduction: Anticoagulants such as heparins and vitamin K antagonists (VKA) are effective for thrombosis prevention and treatment, but are associated with the risk of bleeding and other limitations, spurring the search for improved drugs.

Areas covered: to evaluate the newer anticoagulants, focusing on those tested in phase III clinical trials such as direct oral anticoagulants (DOACs), antisense oligonucleotides (ASO) and warfarin analogues. DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban are licensed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, dabigatran, rivaroxaban and apixaban for postoperative thromboprophylaxis in patients undergoing elective hip or knee arthroplasty and rivaroxaban for secondary prevention of acute coronary syndromes. ASO interfering with Factor XI hepatic synthesis were effective and safe for thromboprophylaxis in elective knee arthroplasty.

Expert opinion: DOACs have overcome some limitations of anticoagulants such as VKA, but are still associated with a risk of bleeding and they lack both standardized and widely available tests measuring their anticoagulant effect and a reversal agent, except for idarucizumab, specific for dabigatran, in case of major or life threatening bleeding or emergency surgery. Agents targeting Factor XI and possibly Factor XII may be ideal anticoagulants, as they can prevent thrombosis with low bleeding risk.     

Transposition of the great arteries: operative outcome in the current era

AIMS: To assess the operative outcome, cardiac and neurodevelopmental sequelae in infants with transposition of the great arteries (TGA) undergoing the arterial switch operation (ASO). METHOD: Cross-sectional review of the 48 consecutive patients operated on in the calendar years 1995 and 1996 was undertaken to obtain recent cardiac, growth and neurodevelopmental parameters, and the mortality results were compared to the entire cohort of infants who underwent the ASO for definitive repair of TGA and double outlet right ventricle at Greenlane hospital between 1984 and 1998. RESULTS: Between January 1995 and December 1996, 48 patients underwent the ASO. 96% were alive, and 88% alive and free from reoperation or significant neurological sequelae at a mean followup interval of sixteen months. Six (13%) had important residual cardiac lesions, of which supra valvular pulmonary stenosis was the most common. Growth parameters at follow-up were normal, as was the neurodevelopmental progress of all but two survivors (96%). CONCLUSION: In the current era, the ASO is a relatively safe procedure with excellent cardiac and neurodevelopmental outcome in the majority of infants.     

On the Connection Between Autoimmunity,tic Disorders and Obsessive-Compulsive Disorders: A Meta-Analysis on Anti-Streptolysin O Titres

Anti-streptolysin O (ASO) titration is useful in the context of autoimmune pathologies, including specific cases of tic and obsessive-compulsive disorders occurring after streptococcal infections. There is currently a lack of consensus on the use of ASO titres; therefore we performed a meta-analysis to systematise available data and clarify the role of ASO titres in the context of neuropsychiatric disorders. A meta-analysis was performed on ASO titration in neuropsychiatric patients, including tic disorders and obsessive-compulsive disorders. Included studies reported numbers of positive subjects, depending on a chosen threshold, or detailed ASO titrations. Three hundred and twenty nine studies were identified, of which 13 were eligible for meta-analysis. Due to limited available data, only tic disorders were evaluated. The odds ratio of finding an abnormal ASO titre in patients was 3.22 (95 % C.I. 1.51–6.88) as compared to healthy controls and 16.14 (95 % C.I. 8.11–32.11) as compared to non-psychiatric patients. Studies using different thresholds were generally concordant. ASO titres were also compared quantitatively, finding an overall difference of the means of 70.50 U/ml (95 % C.I. 25.21–115.80) in favour of patients with tic disorders. Based on current evidence, tic disorders are associated with a significant increase in ASO titres, evident both in a threshold-level perspective and on a quantitative level. These results encourage the systematisation of ASO titration in the context of tic disorders.     

Relative potency of albendazole and its sulfoxide metabolite in two in vitro tests for developmental toxicity: The rat whole embryo culture and the mouse embryonic stem cell test

The benzimidazole carbamate albendazole (ABZ), a potent anthelmintic, is a teratogenic compound in rats. At present it is unclear to which degree this effect is caused by the parent compound or its major metabolite, albendazole sulfoxide (ASO). Both substances were studied separately and in combinations to mimic incomplete bioactivation in two in vitro tests: mouse embryonic stem cell test (EST) and rat whole embryo culture (WEC). In both assays, ABZ and mixtures with ASO induced detrimental effects at lower concentrations compared to ASO alone. While ABZ caused half-maximal effects on cardiomyocyte differentiation at a mean concentration of 0.26μM (EST) and dysmorphogenic development of rat embryos at 3.7μM (WEC), effective concentrations of ASO were similar in both assays (10-13μM). By using WEC and EST we demonstrate that ABZ exhibits stronger inherent embryotoxic potency although ASO might be the proximate teratogen in vivo because of higher plasma concentrations.