消栓肠溶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研究

摘要 目的：研究消栓肠溶胶囊联合依达拉奉右莰醇注射用浓溶液治疗急性脑梗死（ACI）的临床疗效。方法：选取2021年3月-2022年8月间我院诊治的132例ACI患者,按照随机数字表法将患者分为对照组（n=66,依达拉奉右莰醇注射用浓溶液治疗）和观察组（n=66,对照组的基础上接受消栓肠溶胶囊治疗）。治疗14d后,对比两组疗效、卒中量表评分[美国国立卫生研究院卒中量表（NIHSS）、改良Rankin评分量表（mRS）]、脑血流灌注指标[平均流速（TMV）、收缩期峰值流速（PSV）、阻力指数（RI）]、炎症因子水平[正五聚蛋白3（PTX-3）、脂蛋白相关磷脂酶A2（Lp-PLA2）、淀粉样蛋白A（SAA）]水平和血管内皮功能指标[一氧化氮（NO）、内皮素-1（ET-1）、血浆血栓素B2（TXB2）],同时记录两组不良反应发生情况。结果：观察组的临床总有效率高于对照组（P<0.05）。与对照组治疗14 d后相比,观察组的NIHSS、mRS评分、RI、Lp-PLA2、PTX-3、SAA、ET-1、TXB2更低,TMV、PSV、NO更高（P<0.05）。两组不良反应发生率对比未见差异（P>0.05）。结论：依达拉奉右莰醇注射用浓溶液和消栓肠溶胶囊联合治疗ACI,可减轻神经损伤,抑制炎症反应,改善血管内皮功能,促进脑循环恢复,且无明显不良反应。     

Synthesis and biological evaluation of novel pyrazoline-based aromatic sulfamates with potent carbonic anhydrase isoforms II,IV and IX inhibitory efficacy

Herein we report the synthesis of a new series of aromatic sulfamates designed considering the sulfonamide COX-2 selective inhibitors celecoxib and valdecoxib as lead compounds. These latter were shown to possess important human carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties, with the inhibition of the tumor-associated isoform hCA IX likely being co-responsible of the celecoxib anti-tumor effects. Bioisosteric substitution of the pyrazole or isoxazole rings from these drugs with the pyrazoline one was considered owing to the multiple biological activities ascribed to this latter heterocycle and paired with the replacement of the sulfonamide of celecoxib and valdecoxib with its equally potent bioisoster sulfamate. The synthesized derivatives were screened for the inhibition of four human carbonic anhydrase isoforms, namely hCA I, II, IV, and IX. All screened sulfamates exhibited great potency enhancement in inhibiting isoform II and IV, widely involved in glaucoma (K_Is in the range of 0.4–12.4 nM and 17.7 and 43.3 nM, respectively), compared to the lead compounds, whereas they affected the tumor-associated hCA IX as potently as celecoxib.     

1-(4-Methane(amino)sulfonylphenyl)-3-(4-substituted-phenyl)-5-(4-trifluoromethylphenyl)-1H-2-pyrazolines/pyrazoles as potential anti-inflammatory agents

2-Pyrazolins 14a–l and pyrazoles 15a–l were designed as celecoxib analogs for the evaluation of their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. Compounds 14i, 15a, 15d and 15f were the most COX-2 selective derivatives (S.I. = 5.93, 6.08, 5.03 and 5.27 respectively) while the pyrazoline derivatives 14g and 14i exhibited the highest AI activity (ED₅₀ = 190.5 and 160.1 μmol/kg po, respectively).     

Parental size and environmental conditions affect egg capsule production by Nassarius reticulatus (Linnaeus 1758) (Gastropoda: Nassariidae)

In shallow coastal habitats scavenging netted whelks Nassarius reticulatus attached egg capsules to the stipes of red algae Chondrus crispus and occasionally on Furcellaria lumbricalis and Plumaria plumose. In the laboratory egg capsules were laid on aquaria sides and lids by individuals ≥ 21 mm shell length. Larger size classes produced more egg capsules and spawned over a longer period and in doing so partitioned less energy into shell growth. Large netted whelks (25-28.9 mm) produced larger capsules which contained significantly more and larger eggs than those produced by smaller individuals (21-24.9 mm). Egg capsule production continued throughout the year by regularly fed N. reticulatus held at ambient seawater temperatures. Egg production increased in the spring and summer with peak production during June (15 °C), decreased between August and October and resumed again during the winter (November to February at ∼ 7 °C). During the summer (15-16 °C) egg capsules were smaller and contained smaller eggs than those deposited during the winter (7-10 °C), although the number of eggs · capsule⁻¹ was similar. Enforced food limitation reduced the number and size of the egg capsules, the number and size of eggs produced · female⁻¹ and the duration of the breeding period. Hatching success of N. reticulatus egg capsules was high (95%) even at winter seawater temperatures (11-8.5 °C) and the duration of embryonic development was fastest between 15 and 17.5 °C.     

Complement mediated Klebsiella pneumoniae capsule changes

The Gram-negative bacterium Klebsiella pneumoniae is an opportunistic pathogen, which can cause life-threatening infections such as sepsis. Worldwide, emerging multidrug resistant K. pneumoniae infections are challenging to treat, hence leading to increased mortality. Therefore, understanding the interactions between K. pneumoniae and the immune system is important to develop new treatment options.We characterized ten clinical K. pneumoniae isolates obtained from blood of bacteremia patients. The interaction of the isolates with human serum was investigated to elucidate how K. pneumoniae escapes the host immune system, and how complement activation by K. pneumoniae changed the capsule structure. All K. pneumoniae isolates activated the alternative complement pathway despite serum resistance of seven isolates. One serum sensitive isolate activated two or all three pathways, and this isolate was lysed and had numerous membrane attack complexes in the outer membrane. However, we also found deposition of complement components in the capsule of serum resistant isolates resulting in morphological capsule changes and capsule shedding. These bacteria did not lyse, and no membrane attack complex was observed despite deposition of C5b-9 within the capsule, indicating that the capsule of serum resistant K. pneumoniae isolates is a defense mechanism against complement-mediated lysis.     

Acute toxicity of tributyltin to encapsulated embryos of a marine gastropod

The marine gastropod Buccinanops globulosus is known to have high imposex incidence in areas moderately polluted by tributyltin (TBT). Acute toxicity was previously studied in adults but no information is known about embryonic intracapsular development. To estimate the potential effects of organotin pollution on the progeny of B. globulosus, acute toxicity tests were conducted on encapsulated and excapsulated pre-hatching embryos. The lethal median concentration estimated for 96?h (LC₅₀ 96?h) in B. globulosus excapsulated embryos was 196.70?µg?TBTCl?L^?1, while in encapsulated embryos it was 2951.28?µg?TBTCl?L^?1. The LC₅₀ 96?h was 15-fold higher for encapsulated embryos compared to excapsulated embryos, denoting egg capsule protection against pollutants from the external environment. Our results show that TBT pollution can have significant effects in molluscs other than the chronic effect of imposex.     

Sexual performance of male mosquito Aedes albopictus

Issues of male fertility must be addressed to support the development of a sterile insect technique (SIT) programme for the control of Aedes albopictus Skuse (Diptera: Culicidae) populations on Reunion Island in the Indian Ocean. The mating ability of a local strain of Ae. albopictus was tested using several batches of females and different cage sizes under laboratory conditions. Individual males were able to inseminate up to 14 females at an average of 9.5 females per male when exposed to 20 females over 7 days. Males filled between three and 27 spermathecal capsules at an average of 15.5 capsules per male. The average number of females inseminated per male was 5.3 when two virgin females were introduced to one male and replaced every day for 12 days, and 8.6 when 10 virgin females were introduced to one male and replaced every day for 14 days. A continuous decrease in the number of both inseminated females and filled spermathecal capsules was observed over time, until no mating occurred after 14 days. The high number of females inseminated by one male and the duration of male activity may have strong implications for SIT control of mosquitoes.     

酪酸梭菌活菌胶囊辅助治疗对非酒精性脂肪肝病患者氧化应激损伤的保护作用

目的探讨酪酸梭菌活菌胶囊辅助治疗对非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)患者氧化应激损伤的保护作用。方法选取2017年1月至2019年3月我院内科门诊就诊的NAFLD患者76例,随机分为观察组和对照组,各38例。两组患者均给予饮食调整、纠正不良生活习惯和适当运动锻炼。对照组患者给予多烯磷脂酰胆碱胶囊456 mg/次,3次/d,口服。观察组患者在对照组基础上加用酪酸梭菌活菌胶囊0.6 g/次,2次/d,温水口服。两组患者连用8周。检测两组患者治疗前后肝功能指标[丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(γ-GT)]及氧化应激指标[氧化低密度脂蛋白(ox-LDL)、过氧化脂质(LPO)、丙二醛(MDA)]水平的变化。结果治疗8周后,两组患者血清ALT、ALP和γ-GT水平较治疗前明显下降,且观察组下降幅度大于比对照组(均P0.05);同时两组患者血清ox-LDL、LPO和MDA水平明显下降,且观察组患者下降幅度大于对照组(均P0.05)。结论酪酸梭菌活菌胶囊辅助治疗NAFLD患者能降低血清ox-LDL、LPO和MDA水平,抑制氧化应激反应亢进,保护肝功能。     

塞来昔布联合氟尿嘧啶对胰腺癌细胞株SW1990生长抑制作用及其机制研究

目的:研究选择性环氧化酶-2(COX-2)抑制剂塞来昔布联合氟尿嘧啶对胰腺癌细胞株SW1990生长的抑制作用,并对其机制进行初步探讨.方法:实验分为对照组、氟尿嘧啶组、塞来昔布组及两药联合组,将不同浓度的药物分剐作用于胰腺癌细胞株SW1990,MTT法检测各组细胞的生长抑制率,并探索产生最佳细胞生长抑制作用的药物浓度.流式细胞仪检测不同药物作用对肿瘤细胞周期的影响.RT-PCR检测各组细胞Survivin的表达情况.结果:MTT法显示氟尿嘧啶、塞来昔布均能抑制SW1990的生长,且细胞的存活率都随药物浓度的增加而降低.两药联合组对细胞生长的抑制作用更明显.流式细胞仪检测结果显示塞来昔布组、氟尿嘧啶组及两药联合组细胞较对照组G0/G1期细胞比例明显增加,S期和G2/M期细胞比例明显减少.RT-PCR结果显示氟尿嘧啶组、塞来昔布组、联合组都可下调Survivin的表达,以联合组最为明显.结论:塞来昔布联合氟尿嘧啶对胰腺癌SW1990细胞的生长具有抑制作用,其机制可能与下调Survivin的表达从而诱导细胞的凋亡和细胞周期的停滞有关.