抗骨髓炎片对家兔慢性骨髓炎的改善作用研究

目的 观察抗骨髓炎片（KST）对家兔慢性骨髓炎（CO）的改善作用。方法 将金黄色葡萄球菌注入家兔右胫骨骨髓腔内建立CO模型,将CO家兔分为模型组、庆大霉素（60 mg/kg）组及KST高、低剂量（480、240 mg/kg）组,另设假手术组,ig给药。术后第2、4、6周对右胫骨行X-线检查并做诊断分型,采血进行白细胞计数,取血清检测C-反应蛋白（CRP）含量,术后第6周取右胫骨检测核因子κB（NF-κB）的阳性表达。结果 KST高、低剂量组术后第2、4、6周的X-片诊断分型与模型组比较均显著改善,有统计学意义（P<0.05、0.01）;与模型组比较,KST高、低剂量组的白细胞计数、血清CRP含量、胫骨组织NF-κB表达在第2、4、6周均显著降低（P<0.05、0.01）。结论 KST对CO家兔具有保护作用,其机制可能与抑制致病菌、缓解炎症反应、下调炎性反应调控因子NF-κB等环节有关。     

骨炎方对家兔骨感染的预防

摘 要 目的：探讨骨炎方对家兔慢性骨髓炎的预防作用。方法: 家兔右胫骨骨髓腔内注射金黄色葡萄球菌建立慢性骨髓炎模型,分为正常对照组、模型组、庆大霉素组（60 mg·kg-1）、骨炎方高剂量组（3.6 g·kg-1）、骨炎方低剂量组（1.8 g·kg-1）,各组灌胃给药,术后第6周对右胫骨行X线检查并做Laurence评分;术前及术后第2,4,6周采血分别测定白细胞计数、血清溶菌酶（LZM）、血清C 反应蛋白（CRP）含量。结果: 骨炎方高、低剂量组对家兔骨髓炎症状有显著缓解,Laurence评分与模型组比较均有统计学意义（P<0.01）;与模型组比较,骨炎方高、低剂量组的白细胞计数在第2,4,6周均有明显降低（P<0.01）,而血清LZM含量则有明显升高（P<0.05或P<0.01）。与模型组比较,骨炎方高剂量组血清CRP含量在第2,4,6周均有明显降低（P<0.05或P<0.01）,低剂量组血清CRP含量在第4,6周均有明显降低（P<0.05）。与庆大霉素组比较,骨炎方高、低剂量组的白细胞计数在第4周有明显升高（P<0.05或P<0.01）;骨炎方高剂量组的血清LZM含量在第2、4、6周均有明显升高（P<0.01）,低剂量组的血清LZM含量在第2周有明显升高（P<0.05）;骨炎方高、低剂量组的血清CRP含量则在第6周有明显升高（P<0.01）。骨炎方高、低剂量组之间的Laurence评分、白细胞计数、血清LZM含量和CRP含量等差异无统计学意义。结论: 骨炎方对家兔骨感染的预防作用可能与抑制致病菌、提高机体免疫力、减轻炎症反应等途径有关。     

骨炎灵片对急性骨髓炎患者的临床疗效及血清炎性指标的影响

目的 探讨骨炎灵片对急性骨髓炎患者的临床疗效及血清炎性指标的影响。方法 选取2018年1月-2019年6月于南阳市第二人民医院106例急性骨髓炎患者作为研究对象,将所有患者随机分为对照组和观察组,每组各53例。对照组给予行骨开窗减压和持续负压引流术等外科处理,同时给予敏感抗生素静脉滴注,注意补充水和电解质等综合治疗。观察组在对照组治疗基础上口服骨炎灵片,2.4 g/次,4次/d。两组疗程均为1个月。比较两组患者的临床疗效、创面愈合时间、住院时间、疼痛缓解50%时间及外周血白细胞（WBC）、中性粒细胞（N）、超敏C反应蛋白（hs-CRP）及血沉（ESR）水平的差异。结果 治疗后,对照组和观察组总有效率分别为81.13%和94.34%,差异具有统计学意义（P<0.05）。治疗后,观察组在创面愈合时间、住院时间和VAS评分降低50%时间均明显低于对照组,两组比较差异均具有统计学意义（P<0.05）。治疗后,两组患者外周血WBC、N、hs-CRP和ESR水平均显著降低,差异均具有统计学意义（P<0.05）;与对照组相比,观察组外周血WBC、N、hs-CRP和ESR水平显著降低,差异均具有统计学意义（P<0.05）。结论 骨炎灵片治疗急性骨髓炎具有较好的临床疗效,能促进创面愈合,显著缓解机体疼痛和降低炎症指标,值得在临床中推广使用。     

小儿治哮灵片对幼年大鼠哮喘的干预作用

目的 研究小儿治哮灵片对幼年大鼠哮喘模型的干预作用及机制。方法 36只雄性Wistar幼年大鼠随机分为6组：对照组、模型组、醋酸地塞米松（阳性药,1 mg/kg）组和小儿治哮灵片低、中、高剂量（0.32、0.64、1.28 g/kg）组。除对照组外,其余各组以卵清蛋白（OVA）致敏、激发制备幼年大鼠哮喘模型。造模第8天开始ig给药,每天给药1次,给药至造模3周,对照组和模型组ig给予蒸馏水。记录各组大鼠引喘潜伏期并进行行为学评分;检测肺脏器指数;酶联免疫吸附法（ELISA）检测各组幼年大鼠血清中白细胞介素（IL）-4、IL-5、IL-6、免疫球蛋白E（IgE）、γ-干扰素（IFN-γ）、核转录因子（NF-κB）的水平以及肺泡灌洗液中IFN-γ水平。结果 与模型组比较,小儿治哮灵片高、中、低剂量组引喘潜伏期及哮喘行为评分均显著下降（P<0.05、0.01）;肺脏器指数显著下降（P<0.05）;血清IL-4、IL-5、IL-6、IgE、NF-κB水平均显著下降（P<0.01）;血清与肺泡灌洗液中IFN-γ水平显著升高（P<0.01）。结论 小儿治哮灵片抗哮喘作用可能与降低炎性细胞因子分泌有关。     

注射用丹参多酚酸对角叉菜胶诱导的慢性尾部血栓小鼠的抗炎性血栓作用研究

目的 通过ip角叉菜胶（Ca）溶液建立小鼠慢性尾部血栓模型,尾iv给予注射用丹参多酚酸（SAFI）,探究其抗炎症血栓作用。方法 将168只KM雄性小鼠随机分为6组：对照组,模型组,SAFI低、中、高剂量（8.365、16.730、33.460 mg·kg^-1）组,造模同时给药组（即造模的同时予以SAFI给药,其余组于造模后给药,16.730 mg·kg^-1）。连续4 d ip 0.06% Ca（10 mL·kg^-1）制备血栓模型,4 d后,对照组和模型组尾iv 0.9%氯化钠注射液,其余各组分别尾iv相应剂量的SAFI,每天1次,给药7 d。给药开始后每天记录各组小鼠的出栓情况;给药结束后各组小鼠摘眼球取血,试剂盒法检测血清中6-酮-前列腺素F1α（6-keto-PGF1α）、血栓素B2（TXB2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）水平,取尾部组织进行病理切片,HE染色观察组织损伤。结果 模型组小鼠出栓率随时间延长增加,在给药第5天出栓率达到100%;SAFI各剂量组小鼠出栓率均低于同一天的模型组,且低、中、高剂量组小鼠出栓率结果存在一定的剂量相关性;造模同时给药组出栓率均低于同一天的模型组,且相比于同一剂量（中剂量组）出栓率更低。与模型组比较,SAFI中、高剂量组和造模同时给药组血清中TXB2水平显著降低（P＜0.05、0.01、0.001）,6-keto-PGF1α水平显著升高（P＜0.01、0.001）; SAFI低剂量组小鼠血清IL-6水平显著降低（P＜0.05）,中、高剂量组和造模同时给药组小鼠血清TNF-α、IL-1β、IL-6水平显著降低（P＜0.05、0.01、0.001）; SAFI高剂量组、造模同时给药组血栓情况均明显改善。结论 ip 0.06% Ca制备的炎症血栓小鼠模型稳定、可靠,SAFI能改善炎症血栓小鼠血清中6-keto-PGF1α、TXB2、IL-6、IL-1β、TNF-α水平,有效缓解炎性因子导致的血栓症状。     

当归-赤芍配伍对热毒血瘀证模型大鼠的影响

目的 研究当归与赤芍配伍前后及配伍方式对热毒血瘀证模型大鼠的血液流变学及血清IL-6、TNF-α的影响。方法 140只SPF级SD雄性大鼠随机分为14组,即空白组,模型组,当归单煎液高、中、低剂量组,赤芍单煎液高、中、低剂量组,当归-赤芍合煎液高、中、低剂量组,当归-赤芍单煎合并液高、中、低剂量组。给药组连续灌胃给药14 d,第12天采用角叉菜胶（carrageenan,Ca）与脂多糖（lipopolysaccharide,LPS）联合制备大鼠热毒血瘀证模型,检测其血液流变学（全血黏度、血浆黏度、红细胞比容、红细胞变形指数、红细胞聚集指数）、凝血酶原时间、活化部分凝血活酶时间以及炎性因子（IL-6、TNF-α）。结果 与模型组相比,当归-赤芍合煎液高、中剂量组可显著降低各切变率下的全血黏度、血浆黏度、红细胞聚集指数、红细胞比容以及红细胞变形指数（P<0.05或P<0.01）,可显著增加凝血酶原时间及活化部分凝血活酶时间（P<0.01）,同时显著降低IL-6水平与TNF-α水平（P<0.01）。结论 当归-赤芍药对以合煎的方式配伍,能够明显改善Ca-LPS诱导的热毒血瘀证大鼠的血液流变学、凝血功能的异常变化,同时可调节炎性因子水平的异常升高,效果优于单味药。     

美沙拉嗪联合蒙脱石散治疗溃疡性结肠炎的临床治疗效果

目的 探讨美沙拉嗪肠溶片联合蒙脱石散治疗溃疡性结肠炎的临床治疗效果。方法 选取2017年1月-2017年12月在江苏省滨海县人民医院治疗的溃疡性结肠炎患者80例作为研究对象,将患者随机分为对照组和观察组,每组各40例。对照组患者给予柳氮磺吡啶肠溶片,8片/次,3次/d,另给予蒙脱石散,将蒙脱石散置入50 mL的温水内,摇匀后服用,1次/d。观察组患者口服美沙拉嗪肠溶片,4次/d,4片/次;联合蒙脱石散,服用方法同对照组。所有患者均接受8周连续治疗。观察两组患者的临床治疗效果及不良反应发生率,并比较两组治疗前后血清样本中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平。结果 治疗后,观察组患者的临床治疗有效率为92.50%,对照组患者的临床治疗有效率为72.50%,两组比较差异具有统计学意义（P<0.05）。治疗前,两组患者的血清TNF-α及IL-6水平相比,差异均无统计学意义;治疗后,两组血清TNF-α、IL-6水平均显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组患者的血清TNF-α及IL-6水平均显著低于对照组,差异具有统计学意义（P<0.05）。观察组患者治疗期间不良反应发生率为12.50%,对照组患者治疗期间不良反应发生率为32.50%,差异具有统计学意义（P<0.05）。结论 美沙拉嗪肠溶片联合蒙脱石散治疗溃疡性结肠炎的临床治疗效果较好,安全性较高。     

消痔丸对醋酸致肛门溃疡模型大鼠的作用机制研究

目的 探讨消痔丸对醋酸诱导大鼠肛门溃疡模型的药效作用及其可能的作用机制。方法 以醋酸诱导大鼠肛门溃疡模型,将造模成功大鼠分为模型组、消痔丸（0.81、1.62、3.24 g/kg）组、柑橘黄酮片（0.27 g/kg）组和痔炎消片（0.86 g/kg）组,另设置对照组,每组10只。对照组与模型组ig给予同等体积的0.1% CMC-Na溶液。各组连续ig给药10 d,1次/d。观察各组大鼠表观指标,并采用Image J软件计算溃疡面积;苏木素–伊红染色法观察肛门直肠组织病理学,并进行分级评分;酶联免疫吸附法（ELISA）检测大鼠肛门组织中基质金属蛋白酶-9（MMP-9）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）含量;免疫组化法检测肛门组织中诱导型一氧化氮合成酶（iNOS）、转化生长因子β1（TGFβ1）、血管内皮生长因子A（VEGFA）蛋白表达。结果 与模型组相比,消痔丸组可显著改善醋酸所致大鼠肛周溃疡、肿胀、黏液分泌等情况,加快大鼠肛周黏膜上皮修复,溃疡面积缩小,减少间质或黏膜下水肿及炎性细胞浸润和炎性渗出物;消痔丸组可抑制肛周组织中MMP-9、IL-6、TNF-α分泌和iNOS、VEGFA蛋白表达,增加TGF-β1表达（P＜0.05、0.001）。结论 消痔丸对醋酸诱导的肛门溃疡模型治疗作用显著,主要通过抑制IL-6、TNF-α、MMP-9相关细胞因子分泌和iNOS、VEGFA蛋白表达,升高TGF-β1表达,从抗炎消肿、抑制基质降解、促进组织生长因子表达等途径,起到消肿生肌作用。     

柳氮磺吡啶联合地衣芽孢杆菌对溃疡性结肠炎患者血清炎症因子水平的影响

目的 研究柳氮磺吡啶联合地衣芽孢杆菌对溃疡性结肠炎的疗效及其对血清炎症因子水平的影响。方法 选择2017年8月—2018年8月杨凌示范区医院收治的82例溃疡性结肠炎患者作为研究对象,根据入院的顺序将患者用抽签法随机分为对照组和观察组,每组各41例。对照组患者口服地衣芽孢杆菌活菌胶囊,0.5 g/次,3次/d。观察组在对照组的基础上联合口服柳氮磺吡啶肠溶片,6片/次,3次/d。两组均连续治疗12周。观察两组患者的临床疗效,同时比较两组患者的症状改善时间、临床疾病活动指数（CAI）和血清炎症因子水平。结果 治疗后,观察组的总有效率为90.24%,明显高于对照组的70.73%（P<0.05）。治疗后,两组患者的CAI评分均显著降低（P<0.05）;观察组的CAI评分、腹泻消失时间和血便消失时间明显低于对照组（P<0.05）。两组治疗后的肠黏膜Toll样受体4（TLR-4）和血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平均明显降低（P<0.05）,且观察组上述指标明显低于对照组（P<0.05）。结论 柳氮磺吡啶联合地衣芽孢杆菌能改善溃疡性结肠炎患者的炎症水平,安全有效,值得进一步研究。     

雷公藤多苷片联合曲安奈德口腔软膏治疗盘状红斑狼疮的临床研究

目的 探讨雷公藤多苷片联合曲安奈德口腔软膏治疗盘状红斑狼疮的临床疗效。方法 选取2021年1月—2023年5月唐山市人民医院收治的94例盘状红斑狼疮患者,根据随机数字表法将94例患者分为对照组和治疗组,各47例。对照组于早饭后、晚餐后涂抹曲安奈德口腔软膏,0.4 g/次,2次/d,涂抹后1 h内禁食禁饮。治疗组在对照组基础上饭后口服雷公藤多苷片,1～1.5 mg/kg,3次/d。两组持续治疗4周。比较两组临床疗效、主观疼痛程度、病灶面积和血清因子水平。结果 治疗后,对照组总有效率为78.72%,治疗组总有效率为93.62%,组间比较差异显著（P＜0.05）。治疗后,两组视觉模拟法（VAS）评分比治疗前小,病损面积显著缩小（P＜0.05）,且治疗组VAS评分比对照组更小,治疗组病损面积小于对照组（P＜0.05）。治疗后,两组的血清白细胞介素-2（IL-2）水平高于治疗前,血清骨桥蛋白（OPN）、白细胞介素-6（IL-6）水平低于治疗前（P＜0.05）;治疗组的血清IL-2水平高于对照组,血清OPN、IL-6水平低于对照组（P＜0.05）。结论 雷公藤多苷片联合曲安奈德口腔软膏可提高盘状红斑狼疮的疗效,有助于减轻疼痛程度和缩小病损面积,减轻炎症反应。     

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.     

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.