卒中亚型与重组组织型纤溶酶原激活剂治疗急性缺血性脑卒中预后的关系

目的探讨卒中亚型与rt-PA治疗急性缺血性脑卒中预后的关系。方法以收集发病4.5h内给予rt-PA溶栓的急性缺血性脑卒中患者作为研究对象。采用改良的Rankin量表评价神经功能恢复状况,并根据Rankin量表评分分为预后良好组（mRS评分0~1分）及预后不良组（mRS评分2~6分）。记录溶栓后颅内出血、症状性颅内出血及90d时病死率。结果预后良好组（55例）与预后不良组（46例）相比,两组在卒中亚型方面差别无统计学意义（P=0.941）。Logistic多因素回归分析显示卒中亚型与溶栓预后无关（P=0.608,OR为0.605,95%CI为0.089~4.123）,也与症状性颅内出血无关（P=0.267,OR为0.974,95%CI为0.929~1.020）。与大动脉粥样硬化型相比较,心源性栓塞型、小动脉闭塞型、其他型的卒中患者在90d内溶栓预后良好率差异无统计学意义（分别是P=0.987,P=0.763,P=0.578）。结论卒中亚型与急性缺血性脑卒中患者静脉溶栓预后无关。     

超早期rt-PA静脉溶栓对青年急性卒中患者血管再通的影响分析

目的研究超早期重组人组织型纤溶酶原激活剂(rt-PA)静脉溶栓对青年急性卒中患者血管再通的影响。方法选择2013年2月至2015年2月我院收治的92例青年急性卒中患者作为研究对象,按照数字随机法将其分为对照组和观察组两组,每组46例。对照组患者进行常规治疗,观察组患者进行超早期rt-PA静脉溶栓治疗,比较两组患者治疗后神经功能缺损评分改变情况以及血管再通情况。结果治疗后两组患者的神经功能缺损评分均有所改善,但观察组的改善幅度更为明显,且观察组患者治疗后1个月、2个月、3个月血管再通率分别为58.70%、63.04%、67.39%,显著高于对照组的19.27%、28.26%、43.48%,以上数据差异均具有统计学意义(P<0.05)。结论超早期rt-PA静脉溶栓治疗青年急性卒中的效果良好,可显著改善患者的神经功能评分,提高闭塞血管的再通率,安全性好,实用性强,值得临床推荐。     

动脉溶栓与静脉溶栓在大脑中动脉阻塞缺血性卒中患者中的应用比较

目的探讨大脑中动脉阻塞的缺血性卒中患者采用静脉溶栓与动脉溶栓治疗的临床效果。方法对2015年3月至2016年3月本院收治的98例大脑中动脉阻塞的缺血性卒中患者的一般资料进行回顾性分析,所有患者均经临床检查,确诊大脑中动脉阻塞缺血性卒中,患者及家属均知情同意。将其按照治疗方法的不同,分为A组(动脉溶栓)与B组(静脉溶栓)。对比两组治疗效果。结果 A组溶栓治疗时间明显长于B组,结果有显著性差异(P<0.05);A组6例无灌注,7例渗透而无灌注,27例部分灌注,9例完全灌注,血管再通率为73.5%(36/49);B组10例无灌注,10例渗透而无灌注,15例部分灌注,14例完全灌注,血管再通率为59.2%(29/49)。两组血管再通率差异显著(P<0.05);治疗后随访3个月,A组、B组病死率分别为12.2%(6/49)、26.5%(13/49),结果有显著性差异(P<0.05)。结论对大脑中动脉阻塞缺血性卒中患者实施动脉溶栓治疗,能获得较静脉溶栓更为显著的神经功能预后效果,可提升血管再通率,且能降低病死率,值得进行深入研究和推广。     

急性缺血性卒中的血管内溶栓治疗研究进展

急性缺血性卒中的血管内溶栓治疗是目前研究的热点,与静脉溶栓相比,血管内溶栓治疗时间窗较静脉溶栓治疗宽,闭塞血管再通率高,可尽早恢复缺血半暗带（IP）的脑细胞功能,改善患者临床预后。本文就急性缺血性卒中血管内溶栓相关治疗方法的研究进展作一综述。     

阿替普酶静脉溶栓治疗急性缺血性卒中的疗效及安全性评价

目的探讨采用阿替普酶静脉溶栓治疗急性缺血性卒中的疗效,并评价其安全性。方法选取我院2017年1月～2018年6月收治的60例急性缺血性卒中患者作为研究对象,按照随机数字表法将其分为对照组(n=30)和观察组(n=30),对照组给予尿激酶静脉溶栓治疗,观察组给予阿替普酶静脉溶栓治疗,比较治疗前后两组患者神经功能缺损(NIHSS)评分、巴塞尔指数(ADL)分以及纤溶酶原激活物活性的差异;记录两组患者冠脉再通时间、心力衰竭发生率、出血发生率。结果观察组血管溶栓再通总有效率为93.33%(28/30),明显高于对照组73.33%(22/30),差异有统计学意义(P 0.05);治疗前两组患者神经功能缺损评分、巴塞尔指数以及纤溶酶原激活物活性相比差异均无统计学意义(P 0.05),而治疗后两组患者各项指标均较治疗前改善(P 0.05);且治疗后观察组神经功能缺损评分、巴塞尔指数以及纤溶酶原激活物活性均较对照组治疗后改善(P 0.05);观察者冠脉再通时间明显较对照组缩短(P 0.05);且观察组心力衰竭发生率、出血发生率较对照组降低(P 0.05)。结论阿替普酶静脉溶栓治疗急性缺血性卒中效果显著,可提高纤溶酶原激活物活性,改善患者神经功能,缩短溶栓再通时间,减少并发症发生,值得推广。     

不同时间窗重组组织型纤维蛋白酶原激活剂静脉溶栓治疗急性脑梗死合并糖尿病的疗效评价

目的：评价重组组织型纤维蛋白酶原激活剂（ recombinant tissue plasminogen activator ,rt-PA）静脉溶栓治疗不同时间窗急性脑梗死合并糖尿病患者的疗效。方法回顾性分析2013年6月至2014年6月,环湖医院神经内科十七病区收治的急性脑梗死合并糖尿病行静脉溶栓治疗的患者344例,根据发病至治疗时间（ onset to treatment time,OTT）分为＜3 h组（ n ＝152）,3～4…．5 h组（ n ＝104）,4．6～6 h组（ n ＝88）,分别观察静脉溶栓前、溶栓后24 h美国国立卫生院卒中量表（ National Institutes of Health Stroke Scale ,NIHSS）评分以及改良Rankin评分（ modified Rankin Scale,mRS）。结果静脉溶栓前及溶栓后24 h,3组患者NIHSS评分比较,差异均有统计学意义（ P ＜0．05）。发病后90 d对3组患者进行改良Rankin评分,＜3 h组152例患者中神经功能预后良好者100例（65．7％）,预后不良者52例（34．2％）,死亡0例（0％）;3～4．5 h组104例患者中神经功能预后良好者24例（23．1％）,预后不良者80例（76．9％）,死亡4例（3．8％）;4．6～6 h组88例患者中神经功能预后良好者28例（31．8％）,预后不良60例（68．2％）,死亡4例（4．5％）。3组患者神经功能预后情况两两比较差异均有统计学意义（ P ＜0．05）。结论急性脑梗死合并糖尿病患者经rt-PA静脉溶栓近期治疗效果及远期效果均随OTT延长而降低,对于急性脑梗死合并糖尿病患者在时间窗内OTT越短,患者获益越大。     

纤维蛋白原/白蛋白比值与急性缺血性卒中患者rt-PA静脉溶栓后早期神经功能恶化的关系

目的 探讨纤维蛋白原/白蛋白比值（FAR）与急性缺血性卒中（IS）患者重组组织型纤溶酶原激活剂（rtPA）静脉溶栓后早期神经功能恶化（END）的关系。方法 纳入接受rt-PA静脉溶栓治疗的IS患者156例,根据是否 出现END将其分为END组36例和非END组120例。收集患者基线资料,采用Pearson相关分析急性IS患者FAR与 溶栓前美国国立卫生研究院卒中量表（NIHSS）评分的相关性,受试者工作特征（ROC）曲线分析相关指标预测急性IS 患者rt-PA静脉溶栓后END的价值,多因素Logistic回归分析影响急性IS患者rt-PA静脉溶栓后END的危险因素。 结果 IS患者rt-PA静脉溶栓后END发生率为23.08%。END组患者溶栓前NIHSS评分、血糖、白细胞计数、血清纤 维蛋白原（FIB）水平及FAR均明显高于非END组患者,血清白蛋白（ALB）水平明显低于非END组（P＜0.05）。IS患 者 FAR 与溶栓前 NIHSS 评分呈正相关（P＜0.05）。FAR 预测 IS 患者 rt-PA 静脉溶栓后 END 的曲线下面积为 0.806 （0.710~0.902）,高于ALB［0.609（0.494~0.724）］和FIB［0.639（0.524~0.754）］,但低于溶栓前NIHSS评分［0.963（0.931~ 0.994）,P＜0.05］。FAR和溶栓前NIHSS评分升高是影响IS患者rt-PA静脉溶栓后END的独立危险因素（P＜0.05）。 结论 FAR升高与IS患者rt-PA静脉溶栓后END有关,可预测IS患者rt-PA静脉溶栓后END的发生。     

急性心肌梗死静脉溶栓的临床观察

目的 观察静脉溶栓治疗对急性心肌梗死(AMI)患者的预后的影响.方法 将144例AMI患者分为尿激酶静脉溶栓再通组42例,未通组24例和对照组78例.比较分析溶栓再通与未通及非溶栓治疗的AMI患者住院期间的临床疗效.结果 显示溶栓再通组在住院期间2～3周内死亡率明显低于非溶栓组及未通组(P＜0.05),且心绞痛、心力衰竭及严重的心律失常的发生率,溶栓再通组低于未通组及非溶栓组.临床判断梗死相关血管再通率为64%(42/66),0～6 h梗死相关血管溶栓再通率为67%(37/56),6～12 h为50%(5/10).溶栓组无1例过敏反应.结论 用尿激酶静脉溶栓治疗急性心肌梗死是一种安全有效的方法,溶栓治疗能显著改善AMI患者急性期预后,即使临床间接指征判断未通者,其部分指标优于对照组.     

不同病因急性脑梗死血管再通治疗的疗效观察

目的 探讨不同病因急性脑梗死血管再通治疗的疗效.方法 筛选收治的发病6h内急性脑梗死患者51例,其中17例有房颤证据并骤然起病的急性脑梗死患者,首选机械取栓或动脉溶栓,其中机械取栓15例,动脉溶栓2例;34例非房颤相关脑梗死患者给予0.9 mg/kg的静脉rt-PA标准剂量治疗.完成术后24 h、72 h头CT检查,了解术后颅内出血情况;采用术后72 h NIHSS评分改善>4分及90 d改良的Rankin Scale(mRS)评分≤2分作为良好结局指标,评价不同病因急性脑梗死血管再通治疗的风险及疗效.结果 17例房颤相关急性脑梗死入组患者72 h颅内出血3例,其中症状性出血2例占11.8%,造影剂外渗3例,同单纯静脉rt-PA标准剂量溶栓相比颅内出血增加( P <0.05);90 d mRS评分≤2分、获得良好结局者11例占64.7%,明显高于单纯静脉rt-PA标准剂量溶栓获得良好结局的35.3%( P <0.05).结论 房颤相关急性脑梗死患者,超急性期(发病6 h内)首选机械取栓或动脉溶栓治疗是可行的,对于时间窗内的急性脑梗死,应根据不同病因,给予不同优先治疗方案,以期提高患者预后.     

重组组织型纤溶酶原激活剂联合鼠神经生长因子对缺血性脑卒中患者疗效的影响

目的探讨重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓联合鼠神经生长因子对急性缺血性卒中患者的临床疗效。方法选取2015年4月~2017年7月到潮州市人民医院住院治疗并静脉溶栓的急性缺血性卒中并遗留有神经功能缺损患者40例,随机分为观察组与对照组。两组患者均在发病4.5h内在本院静脉使用重组组织型纤溶酶原激活剂(阿替普酶)溶栓治疗,观察组每天给予鼠神经生长因子30μg肌注,并给予缺血性脑卒中常规治疗,对照组只给予缺血性脑卒中常规治疗。并使用NIHSS评估治疗前、治疗7d及治疗14d时疗效。结果两组溶栓前的NIHSS评分无统计学意义(P>0.05),两组的对比有意义,经治疗后7d、14d观察组的NIHSS评分明显低于对照组(P<0.05),具有统计学意义。结论重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓联合鼠神经生长因子能有效改善急性缺血性卒中预后。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.