不同类型胃食管反流病24h食管pH监测的临床研究

目的：研究不同类型胃食管反流病24h食管pH监测指标之间的相关性。方法对符合胃食管反流病（GERD）诊断标准的43例患者,经内镜检查分为反流性食管炎（RE）组、非糜烂性反流病（NERD）组、Barrettt食管组,随后进行高分辨多通道毛细灌注测压检查及食管pH动态监测,比较各组24h食管pH监测指标。结果三组患者食管pH〈4反流次数（次）,反流持续时间≥5 min反流次数（次）、pH〈4总时间, pH〈4百分时间（%）, DeMeester积分差异无统计学意义（P〉0.05）。结论不同类型胃食管反流病食管粘膜损伤与食管酸反流无相关性,食管组织化生与食管酸反流无相关性。     

小剂量红霉素干预早产儿胃食管返流临床研究

目的：探讨小剂量红霉素对早产儿胃食管反流及喂养不耐受的影响.方法：200例胎龄≤34周的早产儿随机分为干预组和对照组各100例,干预组给予红霉素剂量（2.5 mg·kg-1）,用0.9%氯化钠溶液配成浓度为5 mg·ml-1溶液鼻饲q6h,对照组给予等量0.9%氯化钠溶液鼻饲.通过24 h食管pH测定及喂养耐受情况评估,了解两组患儿胃食管反流情况.结果：200例患儿胃食管反流发生率为92.5%（185/200） 鼻饲红霉素治疗后,干预组胃食管反流发生率从94%（94/100）降至32%（32/100）,对照组从91%（91/00）降至77%（77/100）,DeMeester评分干预组从36.9±10.8降至16.8±56.4,对照组从34.3±11.1降至29.0±10.8,两组比较差异均有统计学意义（P〈0.01） 干预组达到出生体重及喂奶量120 ml·kg-1·d-1的天数都比对照组平均提前4 d（P〈0.01）,静脉营养天数及胃储留次数均低于对照组（P〈0.01）.结论：鼻饲小剂量红霉素可以降低胃食管反流的发生率,建议尽早建立胃肠道喂养.     

补肾降浊颗粒对大鼠糖尿病肾病模型肾脏保护作用

目的观察补肾降浊颗粒对大鼠糖尿病肾病模型肾脏的保护作用。方法采用腹腔注射链脲佐菌素法诱发糖尿病肾病大鼠模型，将人选大鼠随机分为5组，每组30只：阳性药对照组（开搏通14mg·kg^-1·d^-1）、补肾降浊颗粒大剂量组（10．4g·kg^-1·d^-1）、补肾降浊颗粒中剂量组（5．2g·kg^-1·d^-1）、补肾降浊颗粒小剂量组（2．6g·kg^-1·d^-1）和模型对照组，同时设正常对照组24只。给药组分别灌胃给药，每日一次，连续12周。模型对照组和正常对照组在同等情况下给予蒸馏水。每隔4周测定体重、血糖、血肌酐和尿肌酐、24小时尿蛋白排泄量、计算内生肌酐清除率。实验8周末、12周末每组随机处死10只大鼠称双肾重量，计算肾指数，并通过电镜观察肾组织病理结构改变。结果实验12周末补肾降浊颗粒能够改善糖尿病肾病大鼠的一般状态，增加体重；减少24h尿蛋白排泄量，与模型对照组比较有显著性差异（P〈0．01）；降低血肌酐及肌酐清除率，与模型对照组比较有显著性差异（P〈0．05）；抑制肾脏肥大，改善肾脏病理改变；结论补肾降浊颗粒能够抑制糖尿病肾病大鼠肾脏肥大及高滤过，降低24h尿蛋白排泄量，改善肾脏病理结构，对肾脏具有保护作用。     

奥美拉唑联合用药治疗以咳嗽为主要表现的胃食管反流病的效果观察

目的探讨奥美拉唑联合用药治疗以咳嗽为主要表现的胃食管反流病的临床疗效。方法选取2012年3月至2013年3月北京市丰台区铁营医院诊治的以咳嗽为主要表现的胃食管反流病患者50例,用随机数字表法分为观察组和对照组,每组25例。对照组服用奥美拉唑胶囊,观察组在对照组的基础上加服雷尼替丁、多潘立酮、硫糖铝悬液。比较2组总有效率以及食管pH值〈4次数、反流超过5min次数、最长反流持续时间、pH值〈4时间占总监测时间的百分率。结果观察组总有效率为96．0％,明显高于对照组68．0％,差异有统计学意义（P〈0．05）。2组治疗后pH〈4次数、反流超过5min次数、最长反流时间、pH值〈4的时间占总监测时间的百分比[观察组：（36±13）次、（2．0±1．1）次、（14±12）rain、（6±3）％;对照组：（45±16）次、（2．7±1．2）次,（17±11）min、（7±5）％]与治疗前[观察组：（79±12）次、（5．7±2．2）次、（38±16）rain、（18±7）％;对照组：（78±16）次、（5．9±2．9）次、（36±12）rain、（20±7）％]比较,差异均有统计学意义（均P〈0．05）。观察组治疗后pH〈4次数、反流超过5min次数、最长反流时间、pH值〈4的时间占总监测时间的百分比均明显低于对照组（P〈0．05）。结论奥美拉唑联合用药治疗以咳嗽为主要表现的胃食管反流病疗效确切。     

Barrett食管的动力学研究

目的对比研究Barrett食管（BE）与正常对照组的动力学差异，揭示BE的动力学改变。方法对比分析22例BE患者与18例正常对照的动力学数据。结果食管动力学检查提示，食管下括约肌压力及屏障压明显降低，酸反流总时间、酸反流总次数以及食管下段pH〈4时间百分比均明显增加（P〈0．05或P〈0．01）。结论屏障压的降低及食管廓清能力的下降导致酸反流的产生，进而促进BE的发生。     

非糜烂性反流病患者食管24h pH值及压力测定的临床意义

目的研究非糜烂性反流病（NERD）患者食管酸暴露与动力学改变特征的临床意义。方法选取有反酸、烧心、胸痛等典型胃食管反流症状而内镜检查阴性的52例（NERD）患者作为研究组,选择无上消化道症状的20例体检者作为对照组,分别行食管24hpH监测检查和食管测压。结果 52例患者中,24hpH监测阳性为40例（76.92%）,且有反流症状患者pH值〈4立位百分比、pH值〈4卧位百分比、反流次数、长反流次数、最长酸反流时间、DeMeester积分均显著高于正常对照组,各指标比较差异有统计学意义（P均〈0.05）。NERD组下食管括约肌（LES）压力显著低于正常组（P〈0.05）,且NERD组食管体部蠕动振幅及频率均低于正常组（P〈0.05）。结论食管长时间的酸暴露,LES压力低下,LES的松弛,食管体部动力障碍可能在NERD的发病中起重要的作用。     

胃食管反流病临床分型诊断的研究

目的：应用24h食管内胆红素与pH监测（食管内双监测）以及食管内镜检查对胃食管反流病（GERD）进行临床分型研究指导临床治疗。方法：按食管胆红素与pH双监测和食管内镜检查的情况结合病人症状对GERD进行临床分型，观察病人在各型的分布。结果：食管内24h胆红素与ph监测结果显示I、Ⅱ型病人的胆红素吸收值≥0.14及pH＜4总时间百分比、酸反流次数和胆汁反流次数较对照组和Ⅲ型明显增加（P＜0．05），而型和Ⅱ型间差异无显著性（P＞0．05），Ⅲ型病人分别为23．3％、65．9％、10．8％。结论：病理性酸反和胆汁反流的破坏作用是导致GERD的重要原因。临床分型对GERD治疗中药物选用具有指导作用。     

不同手术方式对食管癌术后反流的影响研究

目的：分析不同手术方式对食管癌术后反流的影响研究。方法将126例食管癌患者按照随机、自愿的原则分为颈部吻合组、食管床吻合组和腔内吻合组，每组各42例。术后监测每位患者的24 h内的反流次数、〉5 min的反流次数、pH值〈4.0的总时间和最长反流时间。结果颈部吻合组24 h内反流次数、〉5 min的反流次数、pH〈4.0的总时间和最长反流时间均明显高于其他两组，三组间差异有统计学意义（均P〈0.05）。结论食管癌患者术后均存在不同程度的反流现象，建议在重建时适当提高吻合口的位置可以有效减少反流，改善生活质量。     

复发性难治性急性白血病21例临床分析

目的观察氟达拉滨（Flu）、阿糖胞苷（Ara-C）及粒细胞集落刺激因子（G-CSF）（FLAG）方案对复发性难治性急性白血病的疗效与不良反应。方法Flu 30mg·m^-2·d^-1，1～5d；Ara-C1．5g·m^-2·d^-1，5d；在WBC〈1×10^9／L时用G-CSF5μg·kg^-1·d^-1直至WBC〉1．5×10^9／L。治疗21例复发难治急性白血病。结果总有效率81％（17／21），CR57％（12／21），PR24％（5／21），NR14％（3／21）。发生中性粒细胞缺乏16例，持续时间6～18d，血小板〈20×10^9／L 13例，持续时间7～20d。不良反应包括丙氨酸氨基转移酶（ALT）升高、发热、腹泻。结论FLAG方案治疗复发性难治性急性白血病疗效较好，不良反应较少。     

四磨汤口服液对早产儿消化道动力功能影响的临床观察

目的：探讨四磨汤口服液对早产儿消化道动力功能的影响。方法：将42例早产儿随机分成四磨汤及对照组，采用B型实时超声显像法测定其生后第5，10天胃排空变化，并监测胃渚潴留、胆汁反流、腹围异常增加等胃不耐受情况。结果：两组早产儿随日龄增长，50％胃排空时间逐渐缩短。四磨汤组第5天50％胃排空时间短于对照组（P＜0．01），胃潴留的发生率低于对照组（P＜0．05），达到全肠道喂养的时间早于对照组（P＜0．01）。结论：四磨汤口服液能促进早产儿胃排空，减少胃肠不耐受情况的发生。     

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.