巴曲酶注射液对大鼠血栓栓塞性脑卒中急性超早期损伤的保护作用

目的 研究巴曲酶注射液对大鼠血栓栓塞性脑卒中急性超早期的保护作用。方法 自体血凝块闭塞左侧大脑中动脉法制备大鼠血栓栓塞性脑卒中模型,32只造模成功大鼠按神经缺陷程度随机分为4组：模型组及巴曲酶注射液低、高剂量（0.3、1.0 BU/kg）组和阿替普酶（rt-PA,9 mg/kg）组,每组8只,另设假手术组8只。造模1 h后尾iv给药,给药后6 h行神经功能评分,采用核磁共振（MIR）技术进行大鼠脑SE-T2WI序列扫描,测量脑病变范围;给药后24 h评分后取脑进行TTC染色,测量脑梗死范围;给药后6、24 h取血浆,测纤维蛋白原（FIB）浓度。结果 与模型组比较,巴曲酶注射液0.3 BU/kg治疗24 h（P<0.05）、1 BU/kg治疗6、24 h（P<0.05、0.01）显著改善大鼠神经功能评分;给药后6 h MRI结果显示,巴曲酶注射液0.3、1.0 BU/kg显著缩小病变范围（P<0.05、0.01）;给药后24 h TTC结果显示,巴曲酶注射液0.3、1.0 BU/kg显著缩小梗死范围（P<0.05）;巴曲酶注射液0.3、1.0 BU/kg于药后6、24 h均可显著降低血浆FIB浓度（P<0.05、0.01、0.001）。结论 巴曲酶注射液能改善大鼠脑缺血急性期受损神经功能、缩小脑病变范围、降低血浆FIB浓度,具脑保护作用。     

不同年龄段急性心肌梗死患者发病时间特征及预后分析

目的 分析不同年龄段急性心肌梗死(AMI)患者发病时间特征及预后情况。方法 回顾分析2012年1月至2015年6月收治的124例AMI患者临床资料,所有患者均行经皮冠状动脉腔内成形术(PTCA)治疗。将患者按不同年龄段分为A、B、C组3组。A组40例(38~49岁),B组43例(50~75岁),C组41例(76~81岁),比较分析每一组患者的支架植入率、血管开通时间、治疗情况、并发症、发病时间段、心肌标志物及预后情况。结果 3组患者经皮冠状动脉腔内成形术(PTCA)顺利,均获急性心肌梗死冠状动脉内溶栓后血流(TIMI)≥3级分流。A组支架置入率和术后并发症发生率较B、C两组少(P<0.05)。A组罪犯血管开通时间≤12 h,所占比例较B、C两组多(P<0.05)。A组合并糖尿病、高血压和高血脂症比例低于B、C两组(P<0.05),B、C两组并发症比例相当(P>0.05)。A组患者好发高峰时间为6:00~12:00,B、C两组好发高峰时间段0:00~6:00。3组心肌标志物比较中,A组CK升高显著高于B、C两组(P<0.05)。A、B、C3组患者院内病情好转率分别为95%、88.4%、83%,比较差异有统计学意义(P<0.05)。结论 不同年龄段AMI患者发病时间有一定的规律性,50岁以下患者较50岁以上患者院内预后好,应积极治疗;对于高龄患者,应注重术后并发症的预防和治疗。     

不同剂量阿托伐他汀对急性脑梗死患者超敏C反应蛋白S100B蛋白水平及神经功能缺损的影响

目的 观察不同剂量阿托伐他汀对急性脑梗死患者超敏C反应蛋白(hs-CRP)、S100B水平及神经功能的影响,探索大剂量阿托伐他汀对脑梗死急性期治疗的益处。方法 选择急性脑梗死患者96例,随机分为治疗组与对照Ⅰ组、对照Ⅱ组。治疗组服用阿托伐他汀40 mg/d,对照Ⅰ组服用阿托伐他汀20 mg/d,对照Ⅱ组服用阿托伐他汀10 mg/d,其余治疗均相同。分别于治疗前及治疗7、14 d后检测患者血清 hs-CRP和S100B水平,评价神经功能缺损程度。结果 治疗7 d后,治疗组 hs-CRP水平明显下降(P<0.05),对照Ⅰ、Ⅱ组hs-CRP水平下降均不明显(P>0.05)。治疗组S100B水平较治疗前显著下降(P<0.05),对照Ⅰ、Ⅱ组S100B水平变化不明显(P>0.05)。治疗14 d后,治疗组hs-CRP水平进一步下降(P<0.05),对照Ⅰ、Ⅱ组血清hs-CRP水平有明显下降(P<0.05)。治疗组S100B水平进一步下降(P<0.05),对照Ⅰ组S100B水平较治疗前明显下降(P<0.05),对照Ⅱ组S100B水平变化不明显(P>0.05)。治疗后,3组神经功能缺损情况均较治疗前有不同程度改善(P<0.05),与对照组相比治疗组改善更明显。结论 相对20 mg/d、10 mg/d的阿托伐他汀治疗急性脑梗死,40 mg/d的剂量可更明显降低hs-CRP、S100B蛋白水平,改善患者的神经功能缺损,有益于改善患者预后。     

天丹通络胶囊联合阿替普酶治疗急性脑梗死的临床研究

目的 探讨天丹通络胶囊联合注射用阿替普酶治疗急性脑梗死的临床疗效。方法 选取2021年3月—2023年2月在如皋市人民医院就诊的100例急性脑梗死患者，按照随机数字表法将所有患者分为对照组和治疗组，每组各50例。对照组给予注射用阿替普酶，剂量0.9 mg/kg（不超过50 mg），先静脉滴注剂量的10%，剩余的90%静脉滴注60 min，治疗1次，溶栓完成后继续给予基础治疗。治疗组在对照组基础上口服天丹通络胶囊，5粒/次，3次/d。两组连续治疗2周后统计疗效。观察两组的临床疗效，比较两组患者的美国国立卫生研究院卒中量表（NIHSS）评分、超声指标和血清指标。结果 治疗后，治疗组的总有效率94.00%明显高于对照组的总有效率80.00%（P＜0.05）。治疗后，两组的NIHSS评分均显著降低（P＜0.05），治疗组NIHSS评分明显低于对照组（P＜0.05）。治疗后，两组的脑血管储备（CVR）、屏气指数（BHI）显著升高，病灶最长直径显著降低（P＜0.05）；治疗组的CVR、BHI高于对照组，病灶最长直径低于对照组（P＜0.05）。治疗后，两组的血清神经元特异性烯醇化酶（NSE）、正五聚蛋白3（PTX3）、脂蛋白相关磷脂酶A2（Lp-PLA2）水平均低于治疗前（P＜0.05）；治疗后，治疗组的血清NSE、PTX3、Lp-PLA2水平低于对照组，差异有统计学意义（P＜0.05）。结论 天丹通络胶囊联合注射用阿替普酶可提高急性脑梗死的临床疗效，能改善神经功能，提高脑血流灌注，可能与减轻神经细胞炎性损伤有关。     

芪血通络片联合巴曲酶治疗急性脑梗死的临床研究

目的 探讨芪血通络片联合巴曲酶注射液治疗急性脑梗死的临床效果。方法 以2018年1月—2020年5月在开封市中心医院进行治疗的124例急性脑梗死患者为研究对象,根据住院号的奇偶性分为治疗组（62例）和对照组（62例）。对照组给予巴曲酶注射液,首次10 BU巴曲酶注射液与0.9%氯化钠注射液100 mL配伍,隔日一次,维持量为5 BU,隔日一次静脉滴注;治疗组除了给予巴曲酶注射液外还给予口服芪血通络片,4片/次,3次/d。均治疗14 d进行疗效对比。同时对比两组患者BI评分、ADL评分、MoCA评分、血清新蝶呤（Npt）、单核细胞趋化蛋白-1（MCP-1）、亲环素A（CyPA）、可溶性血管细胞黏附分子-1（sVCAM-1）、基质金属蛋白酶-9（MMP-9）水平,血液流变学指标及脑血流动力学指标。结果 治疗后,治疗组在有效率上优于对照组（96.77%比80.65%,P<0.05）。治疗后,两组NIHSS评分、mRS评分显著降低,但ADL评分、MoCA评分、BI评分显著升高（P<0.05）;且治疗后治疗组NIHSS评分、mRS评分低于对照组,而ADL评分、MoCA评分、BI评分高于对照组（P<0.05）。治疗后,两组血清Npt、MCP-1、CyPA、MMP-9、sVCAM-1水平均降低,且以治疗组降低更显著（P<0.05）。治疗后,两组Q_mean、V_mean显著增加,但DR、ZCV及R显著降低（P<0.05）;治疗后,治疗组Q_mean、V_mean高于对照组,但DR、ZCV及R显著低于对照组（P<0.05）。治疗后,两组患者HCT、WBV、FIB及PV均明显降低（P<0.05）;且治疗后,治疗组血流流变学指标低于对照组（P<0.05）。结论 急性脑梗死在给予巴曲酶注射液治疗的同时还进行口服芪血通络片不仅促进机体细胞因子改善,还促进脑血流动力学和血液流变学指标的改善,有利于脑神经功能恢复,促进患者对认知功能的恢复,提高其生活质量,有着很高应用价值。     

蛭蛇通络胶囊联合阿替普酶治疗急性脑梗死的临床研究

目的 探讨蛭蛇通络联合阿替普酶治疗急性脑梗死的临床疗效。方法 选取2019年11月—2022年6月在定州市人民医院住院的120例急性脑梗死患者,随机分为对照组(60例)和治疗组(60例)。对照组患者静脉滴注注射用阿替普酶,0.9 mg/kg,最大剂量不超过90 mg,其中10%于1 min内静脉推注完毕,余药在1 h内静脉泵注。在对照组的基础上,治疗组口服蛭蛇通络胶囊,4粒/次,3次/d。两组用药14 d。观察两组患者临床疗效,比较治疗前后两组患者症状缓解时间,日常自理能力评估量表(Barthel)指数和卒中量表(NIHSS)评分,血清炎性因子肿瘤坏死因子-α(TNF-α)、神经元特异性烯醇化酶(NSE)、白细胞介素-6(IL-6)和同型半胱氨酸(Hcy)水平,及不良反应。结果 治疗后,治疗组患者临床有效率为98.33%,明显高于对照组(81.67%,P<0.05)。治疗后,治疗组临床症状缓解时间均早于对照组(P<0.05)。治疗后,两组患者的Barthel指数评分明显升高,而NIHSS评分明显降低(P<0.05),且治疗组Barthel指数和NIHSS评分明显好于对照组(P<0.05)。治疗后,两组患者血清炎性因子IL-6、NSE、TNF-α、Hcy水平明显降低(P<0.05),且治疗组明显低于对照组(P<0.05)。治疗后,治疗组不良反应总发生率为6.67%,明显低于对照组发生率(15.00%,P<0.05)。结论 阿替普酶联合蛭蛇通络胶囊治疗效果确切,可缓解急性脑梗死症状,患者神经功能损伤程度改善明显,患者自理能力增强,并能降低机体炎性因子。     

丁苯酞软胶囊联合依达拉奉右莰醇治疗急性脑梗死的临床研究

目的 探究丁苯酞软胶囊联合依达拉奉右莰醇注射用浓溶液治疗急性脑梗死的临床疗效。方法 选取2020年10月—2022年4月六安市中医院收治的72例急性脑梗死患者作为研究对象，将所有患者按照随机数字表法分为对照组和治疗组，每组各36例。对照组静脉滴注依达拉奉右莰醇注射用浓溶液，15 mL加入到100 mL生理盐水中，2次/d。治疗组患者在对照组治疗的基础上口服丁苯酞软胶囊，0.2 g/次，3次/d。两组患者均连续治疗14 d。观察两组的临床疗效，比较两组的美国国立卫生研究院卒中量表（NIHSS）评分、Barthel指数、脑血管储备能力（CVR）、血清单核细胞趋化蛋白-1（MCP-1）、基质金属蛋白酶-9（MMP-9）水平。结果 治疗后，治疗组的总有效率为91.67%，对照组的总有效率为72.22%，组间比较差异具有统计学意义（P＜0.05）。治疗后，两组NIHSS评分降低，Barthel指数升高（P＜0.05），治疗组NIHSS评分低于对照组，Barthel指数高于对照组（P＜0.05）。治疗后，两组CVR升高，搏动指数值降低（P＜0.05），治疗组CVR高于对照组，搏动指数值低于对照组（P＜0.05）。治疗后，两组血清MCP-1、MMP-9水平均降低（P＜0.05），治疗组血清MCP-1、MMP-9水平低于对照组（P＜0.05）。结论 丁苯酞软胶囊联合依达拉奉右莰醇注射用浓溶液能改善急性脑梗死患者神经功能，增加脑血管储备能力，减轻炎症反应，安全性较高，值得推广应用。     

注射用瑞替普酶联合还原型谷胱甘肽治疗急性ST段抬高型心肌梗死的效果及安全性

目的 研究注射用瑞替普酶联合还原型谷胱甘肽治疗急性ST段抬高型心肌梗死的效果及安全性。方法 选取2015年2月-2016年2月于湖北监利县人民医院接受治疗的急性ST段抬高型心肌梗死患者90例,按照不同的治疗方式分为A、B、C组,A组患者给予常规治疗,B组患者在常规治疗的基础上给予还原型谷胱甘肽治疗,C组患者在常规治疗的基础上给予注射用瑞替普酶联合还原型谷胱甘肽治疗,比较3组患者的血管再通率;疗效相关指标,包括肌酸激酶同工酶（CKMB）、肌钙蛋白I（cTnI）、左心室舒张末期内径（LVEDd）及左室射血分数（LVEF）;氧化应激相关酶,包括超氧物歧化酶（SOD）和谷胱甘肽过氧物酶（GSH-Px）;不良反应,包括出血、再梗死、心绞痛、心律失常等。结果 C组患者首次治疗后2、6、12 h血管再通率较A、B组显著提高（P<0.05）;与治疗前比较,3组患者治疗后疗效相关指标均得到明显改善（P<0.05）;治疗后组间比较,C组各项指标改善均优于A、B组,差异显著（P<0.05）。B、C组患者治疗后,SOD及GSH-Px均较治疗前显著升高（P<0.05）,B、C组间无明显差异。C组不良反应发生情况明显少于A、B组,差异显著（P<0.05）。结论 注射用瑞替普酶联合还原型谷胱甘肽治疗急性ST段抬高型心肌梗死能有效改善心功能,提高血管再通率,抑制氧化应激反应,减少不良反应发生,临床上值得推广。     

超早期使用丁苯酞注射液对急性脑梗死患者神经功能及侧支循环建立的影响

目的 探讨超早期使用丁苯酞注射液对急性脑梗死患者神经功能及侧支循环建立的影响。方法 选取2014年7月—2017年7月漯河市第二人民医院诊治的急性脑梗死患者86例作为研究对象,按照入院先后顺序分为对照组（42例）和观察组（44例）。对照组给予阿替普酶静脉溶栓治疗,观察组在阿替普酶静脉溶栓前后给予丁苯酞注射液100 mL静脉滴注,2次/d,两次间隔时间为7 h,治疗14 d。比较两组患者治疗前和治疗14 d的临床有效率、侧支循环血流速度,比较两组患者治疗前、治疗1 h、治疗7 d和治疗14 d的美国国立卫生院神经功能缺损评分（NIHSS）和日常生活能力（ADL）评分。结果 观察组的临床有效率为90.91%,对照组的临床有效率为78.57%,观察组显著高于对照组（P<0.05）。两组患者NIHSS评分在治疗1 h、治疗7 d和治疗14 d均显著低于治疗前（P<0.05）,且观察组在治疗1 h、治疗7 d和治疗14 d均显著低于对照组（P<0.05）。两组患者ADL评分在治疗1 h、治疗7 d和治疗14 d均显著高于治疗前（P<0.05）,且观察组在治疗1h、治疗7 d和治疗14 d均显著高于对照组（P<0.05）。两组患者治疗后大脑中动脉（MCA）流速显著加快,大脑前动脉（ACA）和大脑后动脉（PCA）流速显著减慢（P<0.05）;且治疗后观察组MCA流速与对照组相比较快（P<0.05）,观察组ACA和PCA流速与对照组相比较慢（P<0.05）。结论 超早期使用丁苯酞注射液治疗急性脑梗死可显著改善患者的神经功能、提高生活能力,改善侧支循环血流速度,取得较好的临床疗效。     

尿激酶与阿替普酶治疗急性脑梗死的疗效对比

目的 评价阿替普酶与尿激酶治疗急性脑梗死（ACI）的临床疗效。方法 将150例急性脑梗死患者随机分为阿替普酶组75例，尿激酶组75例。两组分别给予阿替普酶和尿激酶进行治疗，应用NIHSS评分系统进行评分，监控2周，观察比较两组的疗效和不良反应发生情况。结果 阿替普酶组基本痊愈20例，显著进步31例，进步18例，总有效率92%；尿激酶组基本痊愈16例，显著进步21例，进步17例，总有效率72%，阿替普酶组总有效率明显高于尿激酶组，两组比较差异有显著性（P<0.05）；治疗前两组NIHSS评分差异无统计学意义；治疗后24 h、1周、2周，两组NIHSS评分均明显低于治疗前，比较差异有统计学意义（P<0.05），治疗后24 h、1周、2周阿替普酶组NIHSS评分均低于尿激酶组，比较差异有统计学意义（P<0.05）。两组并发症及不良反应率比较，阿替普酶组为4%，尿激酶组为17.3%，阿替普酶组明显低于尿激酶组，比较差异有统计学意义（P<0.05）。结论 阿替普酶治疗急性脑梗死疗效确切，不良反应发生率低，值得临床推广。     

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.     

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.     

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.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.