雌三醇及拮抗剂三苯氧胺对兔耳瘢痕增生的影响

目的 建立兔耳增生性瘢痕模型,探讨雌三醇乳膏对兔耳瘢痕的影响及三苯氧胺的拮抗作用.方法 采用新西兰大耳兔24只,在建立模型之前随机分成3组,每组8只:雌三醇组、三苯氧胺组、对照组.造模后,对照组不作处理,雌三醇组给予雌三醇软膏;三苯氧胺组同时给予雌三醇软膏和三苯氧胺.每周观察一次兔耳瘢痕,包括瘢痕硬度、色泽、厚度皮钉大小、数目情况,在术后2周(用药前)及术后5周分别切取3组瘢痕作HE染色及免疫组化,观察瘢痕中成纤维细胞情况及TGF-β1的表达情况.结果 术后5周,雌三醇组瘢痕增生明显,表面凹凸不平、质地硬、色泽偏暗红、厚度增加并有大量皮钉形成;三苯氧胺组瘢痕明显扁平,表面光滑、质地软、色泽接近正常、厚度变薄,较少皮钉形成;对照组在外观上与三苯氧胺相比,仅皮钉数目多于三苯氧胺组.用免疫组织化学方法检测见雌三醇组瘢痕中TGF-β1表达明显高于三苯氧胺组,差异有统计学意义(P＜0.05).对照组TGF-β1表达高于三苯氧胺组,差异有统计学意义(P＜0.05).结论 雌三醇乳膏对兔耳瘢痕有促进增生的作用,并与TGF-β1表达同步.三苯氧胺可以抑制雌三醇导致的兔耳瘢痕增生.     

三苯氧胺、平消胶囊、维生素E联合治疗乳腺增生疗效观察

目的 观察三苯氧胺、平消胶囊、维生素E联合治疗乳腺增生的临床疗效.方法 156例乳腺增生患者随机分成观察组和对照组各78例,对照组给予三苯氧胺和维生素E,观察组在对照组的基础上加用平消胶囊,治疗2个月后观察疗效.结果 观察组总有效率96.2%,高于对照组的79.5%,差异有统计学意义（Х^2=10.238,P＜0.05）;不良反应发生率11.5%,低于对照组的42.3%,差异有统计学意义（Х^2=18.767,P＜0.01）;复发率两组分别为9.0%和23.1%,差异有统计学意义（Х^2=5.764,P＜0.05）.结论 三苯氧胺、平消胶囊、维生素E联合治疗乳腺增生有效率高,不良反应少,复发率低.     

三苯氧胺治疗乳腺增生的疗效及安全性分析

目的：探讨三苯氧胺治疗乳腺增生的疗效及安全性。方法选取2010年12月—2013年12月泸州医学院附属中医医院收治的乳腺增生患者156例,采用随机数字表法将患者分为治疗组与对照组,各78例。治疗组患者予以三苯氧胺治疗,对照组患者予以乳癖消治疗。观察两组患者临床疗效、血清雌二醇（E2）水平及不良反应发生情况。结果治疗组患者总有效率高于对照组,差异有统计学意义（P ＜0.05）;治疗组患者血清 E2水平低于对照组（P ＜0.05）;治疗组患者不良反应发生率低于对照组（P ＜0.05）。结论三苯氧胺治疗乳腺增生的疗效显著,不良反应少,安全性高。     

标本兼治周期辨证用药治疗乳腺增生病

目的 探讨中医标本兼治周期辨证用药治疗乳腺增生病的疗效.方法 将180例乳腺增生病患者随机分为两组,治疗组120例患者采用标本兼治周期辨证服用中药,根据月经周期,经前方疏肝活血、消滞散结以治标,经后方温肾助阳、调摄冲任以治本.对照组60例口服西药三苯氧胺(TAM).2组均以3个月经周期为一疗程,治疗1～3疗程.结果 中医标本兼治周期辨证用药治疗乳腺增生病疗效优于对照组三苯氧胺治疗组(P＜0.05).结论 结合乳腺的生理、病理,运用标本兼治周期辨证用药的中医治则治疗乳腺增生病疗效显著.     

抑制活化素受体样激酶5对增生性瘢痕成纤维细胞中胶原蛋白沉积的影响

目的研究抑制活化素受体样激酶(ALK)5对增生性瘢痕成纤维细胞Ⅰ型胶原蛋白(COL1A2)和α-平滑肌肌动蛋白(α-SMA)表达的影响。方法手术取增生性瘢痕组织进行成纤维细胞体外原代培养,采用不同浓度(1、5、10μM)的ALK5抑制剂CP-639180对增生性瘢痕成纤维细胞干预3 h后,分别采用定量逆转录PCR和Western blot方法检测Ⅰ型胶原蛋白和α平滑肌肌动蛋白的表达。结果与对照组比较,ALK5抑制剂处理后,成纤维细胞中COL1A2的mRNA和蛋白含量均明显降低,且COL1A2的mRNA和蛋白水平与抑制剂的浓度呈反比(P<0.05,P<0.01)。同样,ALK5抑制剂在转录水平和蛋白翻译水平降低了瘢痕成纤维细胞中α-SMA的表达(P均<0.05)。结论应用小分子ALK5抑制剂CP-639180可以抑制增生性瘢痕成纤维细胞分泌Ⅰ型胶原蛋白和α-SMA,进一步抑制胶原纤维的合成,为增生性瘢痕治疗研究提供新的思路。     

结缔组织生长因子在病理性瘢痕成纤维细胞中的表达

要目的探讨结缔组织生长因子(CTGF)人类增生性瘢痕成纤维细胞中的表达与瘢痕纤维化之摘在间的关系。方法应用半定量逆转录聚合酶链反应(RT-PCR)术,测了瘢痕组织原代培养的成纤维细技检胞中CTGFmRNA表达。结果CTGFmRNA在人类增生性瘢痕成纤维细胞中高度表达,与正常皮肤组织的成纤维细胞比较,有显著性差异(P<0.01)。结论CTGF在人类增生性瘢痕成纤维细胞中高度表达,提示其在增生性瘢痕的纤维化进程中起着重要的作用,这为临床上寻找安全、有效的治疗增生性瘢痕提供了新的思路。     

0.05%卤米松软膏联合甲氧沙林片治疗白癜风疗效观察

目的:观察0.05%卤米松软膏联合甲氧沙林片治疗白癜风疗效.方法:根据随机数字表法将符合入选标准的120例患者分成两组,各60例,对照组口服甲氧沙林片0.3～0.6 mg/(kg.d),每3天1次,服药2小时局部照射黑光(窄谱中波紫外线)30秒,强度以发生轻度红斑反应为宜,实验组在对照组治疗的基础上加用0.05%卤米松软膏,两组均连续治疗3个月.结果:实验组和对照组有效率分别为73.33%和45.0%,差异有显著性(P＜0.01).结论:0.05%卤米松软膏联合甲氧沙林片治疗白癜风疗效较好.     

消癖散结汤联合三苯氧胺治疗乳腺增生症76例

目的观察消癖散结汤联合三苯氧胺治疗乳腺增生病的疗效。方法治疗组76例,用消癖散结汤加三苯氧胺治疗,对照组75例,单用三苯氧胺治疗,进行临床比较。结果治疗组与对照组总有效率和不良反应比较,两组比较差异有统计学意义(P<0.05)。结论消癖散结汤联合三苯氧胺治疗乳腺增生症治疗乳腺增生病疗效显著,且不良反应少。     

微小 RNA-4463对人瘢痕疙瘩成纤维细胞增殖和侵袭的影响

目的 研究微小RNA-4463(miR-4463)对人瘢痕疙瘩成纤维细胞增殖、迁移、侵袭的影响以及机制.方法 收集延安大学附属医院2017年12月至2019年6月整形手术病人40例,每例切除瘢痕疙瘩组织1个以及邻近正常皮肤组织1个,利用定量聚合酶链反应(qPCR)检测人正常成纤维细胞和瘢痕疙瘩成纤维细胞中miR-4463的表达量;将miR-4463模拟物对照质粒和miR-4463模拟物分别在Lipofectamine 2000介导下转染入瘢痕疙瘩成纤维细胞,分为miR-NC组和miR-4463组;常规培养的瘢痕疙瘩成纤维细胞作为对照;qPCR检测转染后miR-4463的表达量;qPCR检测上调miR-4463对瘢痕疙瘩纤维化相关基因Col 1 A1、Col 3 A1表达的影响;细胞计数试剂盒(CCK-8)检测上调miR-4463对瘢痕疙瘩成纤维细胞增殖的影响,Transwell实验检测细胞的迁移、侵袭;采用TargetScan软件预测miR-4463与B细胞淋巴瘤-2(Bcl-2)相关的致病基因BAG4的靶向关系,双荧光素酶报告基因进一步进行验证.结果 miR-4463在瘢痕疙瘩成纤维细胞中的表达量较人正常成纤维细胞显著降低[(0.218±0.036)比(1.000±0.071),P<0.05];与对照组相比,转染miR-4463模拟物明显增加瘢痕疙瘩成纤维细胞中miR-4463的表达量[(1.000±0.073)比(3.313±0.242),P<0.05];上调miR-4463显著抑制瘢痕疙瘩纤维化相关基因Col 1 A1[(1.000±0.065)比(0.334±0.010)]、Col 3 A1[(1.000±0.070)比(0.301±0.008)]的表达量(P<0.05);上调miR-4463抑制瘢痕疙瘩成纤维细胞增殖[(0.836±0.081)比(0.656±0.072),P<0.05],降低其迁移[(153.269±12.471)个比(82.363±7.254)个]、侵袭细胞数[(73.623±6.451)个比(36.459±3.235)个](P<0.05);BAG4是miR-4463下游靶基因.结论 miR-4463可能通过调控BAG4抑制细胞外基质中纤维化相关胶原基因的表达,抑制瘢痕疙瘩成纤维细胞增殖、迁移、侵袭.     

乙氧苯柳胺软膏联合卤米松乳膏治疗神经性皮炎疗效观察

目的 观察乙氧苯柳胺软膏联合卤米松乳膏治疗神经性皮炎的临床疗效.方法 106例患者随机分为治疗组和对照组各53例,治疗组每日晨起和晚上临睡前外用乙氧苯柳胺软膏各1次,中午外用卤米松乳膏;对照组单纯外用卤米松乳膏,每天2次,均3周为1个疗程,观察2组临床疗效及不良反应.结果 治疗1周后治疗组总有效率为28.3%高于对照组的15.1%,差异有统计学意义(P<0.05).治疗3周后治疗组总有效率为88.7%高于对照组的62.3%,差异有统计学意义(P<0.05).治疗组发生不良反应2例,对照组发生11例均无需停药或特殊处理,不影响继续治疗.结论 乙氧苯柳胺软膏联合卤米松乳膏外用治疗神经性皮炎,临床疗效显著,安全性高,不良反应小,值得临床推广应用.     

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.