子宫动脉栓塞术在子宫瘢痕妊娠患者清宫术中的应用效果

目的 探讨子宫动脉栓塞术（UAE）在剖宫产瘢痕妊娠（CSP）患者清宫中的有效性与安全性。方法 回顾性分析2009年6月至2016年12月安徽医科大学附属巢湖医院收治的确诊瘢痕妊娠患者50例临床资料,将其中30例行"子宫动脉栓塞术+刮宫术"患者作为A组,20例行"药物治疗+刮宫术"患者作为B组,比较两组患者术中出血量、住院时间、术后阴道流血时间以及月经恢复正常时间。结果 A组患者术中中位出血量低于B组（10 mL vs 165 mL）,差异有统计学意义（Z=5.643,P=0.001）。A组患者术后阴道流血时间（5.87±1.57）d短于B组（7.55±1.54）d,差异有统计学意义（t=3.744,P=0.001）。不良反应监测,A组17例患者出现了下腹痛,其中4例低热的症状,予以对症治疗后2~4 d缓解。A组患者住院费用（10 369.50±436.30）元高于B组（5 407.30±365.20）元,差异有统计学意义（t=42.032,P=0.001）。结论 子宫动脉栓塞术在剖宫产瘢痕妊娠患者清宫中安全有效,可缩短患者的住院时间和恢复期时间,但治疗费用较高。     

PEG-PLA-α-细辛脑纳米粒经鼻腔、静脉给药后的药动学研究

目的 采用与静脉注射对比的方式,研究聚乙二醇-聚乳酸-α-细辛脑纳米粒（PEG-PLA-α-细辛脑纳米粒）鼻腔给药后在大鼠体内的药物动力学。方法 以大鼠为动物模型,采用血药动力学、脑药动力学及荧光标记法对比研究PEG-PLA-α-细辛脑纳米粒经鼻腔给药与静脉注射后药物/纳米粒在大鼠体内的分布情况。结果 PEG-PLA-α-细辛脑纳米粒静脉注射及鼻腔给药后血浆中的AUC_（0-∞）分别为（11032.4±1 827.1）ng·mL^-1·min及（5 992.9±717.5）ng·mL^-1·min,C_max分别为（421.9±100.2）ng·mL^-1及（171.7±26.3）ng·mL^-1,PEG-PLA-α-细辛脑纳米粒鼻腔给药后的绝对生物利用度F为54.3%。PEG-PLA-α-细辛脑纳米粒静脉注射后α-细辛脑在脑组织中的C_max与鼻腔给药后α-细辛脑在脑组织中的浓度C_max分别为（217.9±29.9）ng·mL^-1及（334.2±62.7）ng·mL^-1,PEG-PLA-α-细辛脑纳米粒静脉注射与鼻腔给药后的AUC_brain/AUC_plasma值分别为1.37和2.85,且两者具有统计学意义。PEG-PLA-α-细辛脑纳米粒鼻腔给药后的药物脑靶向效率及鼻-脑传递百分比分别为208.03%及52.01%。荧光标记法结果显示,PEG-PLA-α-细辛脑纳米粒鼻腔给药后脑靶向性比静脉注射后更强。结论 PEG-PLA-α-细辛脑纳米粒适合于鼻腔给药治疗脑部疾病。     

盐酸环丙沙星壳聚糖纳米粒原位凝胶的制备与评价

目的 制备盐酸环丙沙星壳聚糖纳米粒原位凝胶，并评价其抑菌及创面愈合效果。方法 采用复乳法制备盐酸环丙沙星壳聚糖纳米粒，采用2因素2水平全因子析因实验设计考察了壳聚糖相对分子质量（X₁）和壳聚糖质量浓度（X₂）对壳聚糖纳米粒的药物包封率（Y₁）、粒径分布（Y₂）、多分散系数（Y₃）和Zeta电位（Y₄）的影响；并以泊洛沙姆407作为凝胶基质制备盐酸环丙沙星壳聚糖纳米粒原位凝胶。通过抑菌圈实验比较盐酸环丙沙星乳膏和盐酸环丙沙星壳聚糖纳米粒原位凝胶对金黄色葡萄球菌和铜绿假单胞菌的抑菌活性；使用无菌活检穿刺针在大鼠背部造成直径为5 mm的皮肤全切除的圆形人工创面，并使用金黄色葡萄球菌和铜绿假单胞菌的培养基感染24 h，建立大鼠创面模型，将模型大鼠随机分为模型组、盐酸环丙沙星乳膏组和盐酸环丙沙星壳聚糖纳米粒原位凝胶组，模型组大鼠创面未接受任何处理，给药组大鼠每2天给药1次，每次给药量均约为1 mg，观察并记录每组大鼠创面脱痂时间和愈合时间。结果 选择低相对分子质量壳聚糖、壳聚糖质量浓度为2.0 mg·mL^-1制备盐酸环丙沙星壳聚糖纳米粒，其中盐酸环丙沙星质量浓度为50.0 mg·mL^-1，其包封率为（85.3±0.9）%，平均粒径为（354.7±15.7）nm，PDI为0.357±0.014，Zeta电位为（22.2±0.5）mV，呈球状分布；盐酸环丙沙星壳聚糖纳米粒原位凝胶和盐酸环丙沙星乳膏对金黄色葡萄球菌的抑菌圈直径分别为（38.4±0.2）、（29.2±0.3）mm，对铜绿假单胞菌抗菌圈直径分别为（41.3±0.6）、（32.1±0.1）mm；大鼠创面给予盐酸环丙沙星壳聚糖纳米粒原位凝胶后，其脱痂时间和愈合时间均较模型组和盐酸环丙沙星乳膏组显著缩短（P<0.05）。结论 成功制备盐酸环丙沙星壳聚糖纳米粒原位凝胶，其可以抑制创面细菌繁殖、加速伤口愈合。     

糖复康宁提取物对2型糖尿病大鼠的降糖作用研究

目的 研究中药复方糖复康宁提取物2糖尿病模型大鼠的降血糖作用。方法 分别以遗传性ZDF模型大鼠和链脲佐菌素（STZ）联合高糖高脂饲料诱导的SD大鼠为此次研究的2型糖尿病模型动物,ig给予低、高剂量（5.0、10.0 g生药/kg）的糖复康宁提取物,金芪降糖片（455 mg/kg）作为阳性药,连续给药42 d,每周测定空腹血糖、给药第38天测定葡萄糖耐量。结果 ZDF模型结果显示,模型组大鼠血糖值波动幅度保持在10%以内,显著高于对照组（P<0.01）;给药42 d后,与模型组比较,各给药组血糖均显著下降（P<0.01）,金芪降糖片及糖复康宁提取物低、高剂量组血糖下降率分别为（35.9±8.4）%、（22.1±11.1）%、（50.0±9.1）%;STZ模型结果显示,模型组大鼠血糖一直维持在较高水平（21.1~21.6 mmol/L）,变化幅度相对稳定,显著高于对照组（P<0.01）;给药42 d后,与模型组比较,各给药组血糖均下降,其中糖复康宁提取物低、高剂量组差异显著（P<0.01）;金芪降糖片及糖复康宁提取物低、高剂量组血糖下降率分别为（18.6±5.7）%、（21.6±7.2）%、（51.7±20.2）%。糖复康宁提取物低、高2个剂量组血糖曲线下面积（AUC）与模型组比较均显著下降（P<0.05、0.01）。结论 中药复方糖复康宁对2种2型糖尿病模型均发挥显著降糖效果。     

临床护理路径在小儿腹泻护理中的应用效果

目的 探讨临床护理路径在小儿腹泻护理中的应用效果。方法 选取2015年4月至2015年12月阜阳市第二人民医院住院的108例腹泻患儿,随机分为两组,观察组（54例）和对照组（54例）。观察组实施临床护理路径,对照组给予常规的护理。结果 观察组止泻时间、住院时间较对照组短[（3.32±1.03）d vs（4.12±1.06）d,（5.42±1.06）d vs（6.13±1.08）d],差异有统计学意义（t=3.9775,P < 0.001;t=3.4478,P < 0.001）;观察组住院费用低于对照组[（3 014.98±752.97）元vs（3438.12±671.33）元],差异有统计学意义（t=3.0824,P < 0.05）;观察组复发率及满意度均优于对照组,差异有统计学意义（P < 0.05）。结论 将临床护理路径应用于小儿腹泻护理过程中,能改善护理质量,具有良好的临床护理效果。     

氢溴酸樟柳碱注射液大鼠组织分布和Beagle犬药动学研究

目的 研究氢溴酸樟柳碱注射液在大鼠体内的组织分布情况和Beagle犬体内的药动学特征。方法 SD大鼠单次iv氢溴酸樟柳碱注射液5 mg/kg,于给药后5、30、60、90、180 min处死大鼠,取血浆、心、肝、脾、肺、肾、脑、胃、小肠、骨骼肌、脂肪、卵巢、子宫、睾丸。Beagle犬单次iv氢溴酸樟柳碱注射液0.1、0.3、0.9 mg/kg,给药后5、10、20、30、45 min和1.0、1.5、3.0、5.0、7.0、10.0 h静脉采血。采用高效液相色谱-质谱联用法（LC-MS）测定各时间点血浆及各组织中氢溴酸樟柳碱的浓度,统计矩法计算氢溴酸樟柳碱在犬体内的药动学参数。结果 大鼠肾、胃氢溴酸樟柳碱峰浓度最高,分别为（1 967.6±569.4）（2 316.9±952.6） ng/mL,其次为血浆、小肠、肺、肝、脾、卵巢、心、子宫、骨骼肌,而脂肪、睾丸和脑峰浓度最低,低于200 ng/mL。除胃在30 min达峰外,其余组织均在5 min达峰,之后快速下降。Beagle犬iv氢溴酸樟柳碱注射液后,0.1、0.3、0.9 mg/kg组达峰浓度（C_max）分别为（43.3±8.6）、（117.9±40.2）、（348.6±40.0） ng/mL,药时曲线下面积（AUC_0~t）分别为（35.9±6.6）、（159.6±56.6）、（443.3±50.3） ng·h/mL,半衰期（t_1/2z）分别为（0.9±0.3）、（1.5±0.9）、（1.1±0.2）h,清除率（Cl_z）分别为（20.9±5.3）、（17.9±7.6）、（19.4±2.2）×10⁵ L/（h·kg）,表观分布容积（V_z）分别为（24.6±7.0）、（37.0±18.5）、（31.3±4.3）×10⁵ L/kg。结论 氢溴酸樟柳碱在大鼠体内的分布与器官血流量、药物水溶性、生理屏障等因素具有明显相关性;在犬体内血浆清除率和组织分布程度均较高,血浆消除较快,无蓄积性。     

马来酸麦角新碱注射液对疤痕子宫孕产妇术后子宫复旧的影响

目的 探讨马来酸麦角新碱注射液在疤痕子宫孕产妇术后子宫复旧的有效性。方法 以60例具有剖宫产指征的疤痕子宫患者为研究对象。将患者随机分成观察组和对照组,产后分别给予马来酸麦角新碱和缩宫素治疗3 d。观察两组术后子宫大小变化、出血量、宫腔积液情况及恶露消失时间。结果 术后3、42 d观察组子宫大小三径之和分别为（29.9±2.0）cm、（15.8±±1.2）cm,显著低于对照组的（32.6±2.8）cm、（18.1±1.5）cm（P<0.05）;观察组术后24、48 h出血量、42 d宫腔积液发生率、产后恶露消失时间均显著少于对照组（P<0.05）。结论 马来酸麦角新碱可有效修复剖宫产后子宫,减少术后出血量、产后宫腔积液发生率及缩短恶露消失时间,提高子宫复旧效率。     

荭草苷对大鼠心室肌细胞钠通道的影响

目的 研究荭草苷（orientin,Ori）对大鼠心室肌细胞钠通道电流（I_Na）的影响,探讨Ori在离子通道层面的抗心律失常机制。方法 使用Langendorff恒温恒压灌流装置、单酶解消化法分离大鼠心室肌细胞,应用全细胞膜片钳技术记录、观察不同浓度Ori作用前后大鼠心室肌细胞钠通道电流（I_Na）的变化。结果 低于2 μmol·L^-1的Ori对I_Na无明显影响,3,10,30 μmol·L^-1的Ori使I_Na的I-V曲线显著上移,峰值钠电流（I_Na-Peak）由给药前的（-81.49±3.9）pA/pF依次变为（-74.38±4.1）pA/pF,（-63.05±2.8）pA/pF和（-55.35±3.2）pA/pF;Ori使激活曲线右移、失活曲线左移,失活后恢复曲线显著右移,最大半数激活电位（V_1/2-ac）由给药前的（-53.66±4.12）mV分别变为（-44.64±1.9）mV,（-38.95±1.7）mV和（-30.21±1.5）mV;最大半数失活电位（V_1/2-in）由给药前的（-51.68±0.76）mV分别变为（-60.17±1.5）mV,（-68.51±1.4）mV和（-75.22±1.37）mV,恢复时间（τ）由给药前的（18.38±0.84）ms分别变为（24.53±1.4）ms,（35.25±1.3）ms和（68.75±1.58）ms。结论 Ori能浓度依赖性抑制大鼠心室肌细胞的I_Na,并能显著影响其激活、失活及失活后恢复的动力学特征。     

阿加曲班不同给药方式超早期治疗急性缺血性脑卒中的疗效及安全性观察

目的 探索阿加曲班不同给药方式对超早期急性缺血性脑卒中患者的疗效及安全性。方法 回顾性选取2019年2月—2020年11月在肇庆市第一人民医院神经内科住院的急性缺血性脑卒中患者64例为研究对象,根据给药方式不同将患者分为静脉滴注组（静滴组）和微泵＋静脉滴注组（微泵＋静滴组）,静滴组患者给予阿加曲班注射液,10 mg阿加曲班注射液加入0.9%氯化钠注射液250 mL中,静脉滴注给药,每天2次,连续给药（7±1）d;微泵＋静滴组患者给予阿加曲班注射液,持续微泵（10 mL·h^-1）24 h或者48 h,其后采用10 mg阿加曲班注射液加入0.9%氯化钠注射液250 mL中,静脉滴注给药,每天2次,连续给药（5±2）d。比较两组患者临床治疗效果及不良反应。结果 静滴组总有效率（55.88%）高于微泵＋静滴组（53.55%）,但差异无统计学意义（P＞0.05）。两组患者出院时美国国立卫生研究院卒中量表（NIHSS）评分均低于本组入院时NIHSS评分（P＜0.05）,两组间出院时NIHSS评分比较,差异无统计学意义（P＞0.05）。两组患者出院时改良Rankin量表（MRS）≤1分的患者占比比较,差异有统计学意义（P＜0.05）,静滴组占比更高。两组患者出院时MRS评分≤2分的患者占比比较,差异无统计学意义（P＞0.05）。两组均未发生出血事件及新发心脑血管事件。结论 阿加曲班静脉滴注给药治疗急性缺血性脑卒中的疗效显著,安全性高。     

17-甲氧基-7-羟基-苯骈呋喃查耳酮对小鼠心室肌细胞膜钠电流的影响

目的 观察17-甲氧基-7-羟基-苯并呋喃查耳酮（YLSC）对小鼠心室肌细胞膜上钠电流的影响。方法 采用Langendorff逆行主动脉灌流法急性分离昆明小鼠心室肌细胞,全细胞膜片钳技术记录心室肌细胞膜钠电流（INa）在灌流YLSC前后的变化情况。结果 YLSC灌流可使INa的电流幅值减小,I-V曲线上移,但I-V曲线形状、最大激活电位和反转电位基本不变。INa的电流密度在膜电位-40 mV达到最大峰值,给药前的峰电流密度值为（-22.31±2.20） pA/pF,400 μmol·L^-1 YLSC灌流给药后为（-10.64±0.97） pA/pF,与给药前比较有显著差异（n=5,P<0.05）,对钠电流的抑制率为（48.9±3.6）%;400 μmol·L^-1 YLSC给药前后的半数激活电压分别为（-49.51±1.22） mV和（-48.13±2.34） mV,斜率因子分别为2.43±0.36和3.39±0.64,给药前后无显著差异（n=5）。YLSC使失活曲线左移,给药前后半数失活电压分别为（-73.29±1.09） mV和（-76.79±1.62） mV,斜率因子分别为-12.13±2.15和-11.45±1.91,给药前后有显著差异（n=5,P<0.05）。结论 YLSC能通过降低钠通道失活电压,促进钠通道失活而抑制钠通道电流。     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.