合生元长期治疗肝硬化的肠道微生态变化

目的观察肝硬化患者粪便中菌群的情况,为了解肝硬化患者肠道菌群的变化比较肝硬化患者与健康对照组之间的肠道微生态的差异进行综合分析比较。给予合生元(乳果糖和双歧三联活菌片)治疗后观察对比治疗组与肝硬化对照组肠道微生态的变化。方法收集2012年3月至2014年12月烟台市莱阳中心医院感染科所收治的肝硬化患者78例,随机分为肝硬化对照组和合生元组,合生元组在常规保肝抗病毒的基础上给予双歧三联活菌片(1.5 g,1天3次)及乳果糖(10 mL,1天3次),疗程为96周,肝硬化对照组,仅给予保肝、抗病毒、白蛋白等常规治疗。并以15例同期健康在校大学生作为健康对照组。测定治疗前后肠道菌群菌落计数,并用秩相关检测法进行分析。结果肝硬化组患者与正常对照组相比存在不同程度的肠道菌群失调,临床表现主要为:双歧杆菌减少(10.10±0.95比8.10±1.23,P<0.05)。给予合生元治疗后,合生元组双歧杆菌较对照组明显增多(9.98±0.85比8.40±1.05),差异有显著性(P值均<0.05)。结论根据研究发现肝硬化患者临床中存在肠道菌群失调的现象。益生菌制剂能有效改善临床肝硬化患者肠道菌群失调的表现症状。     

双歧三联活菌对肝硬化患者肠道菌群和血浆内毒素的影响

目的探讨双歧三联活菌对肝硬化患者肠道菌群、血浆内毒素和肝功能的影响,方法选择60例乙型病毒性肝炎肝硬化患者,随机分为对照组和治疗组．对照组予以常规保肝治疗,治疗组在对照组常规保肝治疗的基础上加服双歧三联活菌胶囊,每日2次,每次2粒,疗程为2周。观察两组患者治疗前后肠道菌群菌落计数、血浆内毒素和肝功能变化。结果治疗组患者口服双歧三联活菌制剂2周后,肠球菌、双歧杆菌和乳杆菌的菌落数均较治疗前明显增加,而酵母样真菌菌落数较治疗前显著降低,同时患者血浆内毒素水平和血浆中ALT和AST较治疗前明显下降。而对照组患者治疗前后肠道菌群、血浆内毒素水平和血浆中ALT和AST无明显变化。结论口服双歧三联活菌胶囊可迅速纠正肝硬化患者存在的肠道菌群失调,并继而降低其血浆内毒素水平和改善肝功能,对肝硬化有显著的辅助治疗作用。     

双歧杆菌三联活菌胶囊联合加味逍遥散治疗对IBS患者临床症状、胃肠功能及肠道微生态功能的影响

目的探究双歧杆菌三联活菌胶囊联合加味逍散治疗肠易激综合征(IBS)的效果及对患者临床症状、胃肠功能、肠道微生态功能的影响。方法 84例IBS患者,按照治疗方式不同分为试验组与对照组,各42例。对照组给予双歧杆菌三联活菌胶囊治疗,试验组在对照组治疗基础上联合加味逍遥散治疗。对比两组患者临床疗效、治疗前后肠道菌群变化及复发情况。结果试验组治疗总有效率为92.86%,高于对照组的76.19%,差异具有统计学意义(P<0.05)。治疗后,试验组患者乳酸杆菌(8.18±1.05)CFU/g、双歧杆菌(8.89±1.24)CFU/g、肠杆菌(7.16±0.86)CFU/g、肠球菌(5.51±0.74)CFU/g、酵母菌(4.36±0.52)CFU/g、大肠杆菌(8.11±1.11)CFU/g,均优于对照组的(6.69±0.86)、(7.87±0.94)、(8.48±1.21)、(6.91±0.86)、(4.94±0.61)、(8.59±1.22)CFU/g,差异均具有统计学意义(P<0.05)。试验组复发率为16.67%,显著低于对照组的38.10%,差异具有统计学意义(P<0.05)。结论单用双歧三联活菌胶囊长期疗效较差,可选择联用加味逍遥散提高临床效果,增强长期疗效,同时能够维持肠道微环境稳定、提高胃肠功能,以及加快促进肠道正常菌群生长。     

肝硬化患者口服四联活菌片对肠道菌群和血浆细胞因子的影响

目的探讨肝硬化患者口服四联活菌片（思连康）对肠道菌群和血浆细胞因子的影响,方法选择80例肝硬化失代偿期患者,随机分为对照组和观察组,对照组予以予常规保肝治疗,观察组在此的基础上加服思连康片,1次1.5g,每天3次口服,疗程均为4周。观察两组患者治疗前后肠道菌群菌落计数和血浆细胞因子的变化。结果观察组患者口服四联活菌片4周后,肠道菌群发生显著变化,双歧杆菌和乳杆菌的菌落数均较治疗前明显增加,而酵母样真菌菌落数均较治疗前显著降低。同时患者血浆IL-6和TNFα-水平较治疗前明显下降。而对照组患者治疗前后肠道菌群、血浆IL-6和TNFα-水平无明显变化。结论肝硬化患者口服四联活菌片能调节肠道菌群失调,降低血浆细胞因子水平,对肝硬化有显著的辅助治疗作用。     

双歧杆菌三联活菌散辅助利巴韦林颗粒对改善轮状病毒感染肠炎患儿肠道菌群与肠黏膜通透性的影响

目的:探究双歧杆菌三联活菌散辅助利巴韦林颗粒对改善轮状病毒感染肠炎(Rotavirus enteritis,RVE)患儿肠道菌群与肠黏膜通透性的影响.方法:选取医院2018年4月-2019年12月临床治疗的RVE患儿106例病历资料,按治疗方法的不同将其分为对照组和观察组,每组53例;对照组患儿给予利巴韦林颗粒和蒙脱石散治疗,而观察组患儿在对照组的基础上加用双歧杆菌三联活菌散辅助治疗,比较2组患儿治疗前后肠道菌群菌落数、免疫功能和相关肠黏膜指标测得值的变化情况.结果:治疗前2组患儿肠道菌群菌落数(大肠埃希菌、双歧杆菌、乳杆菌数)、免疫功能指标如血清免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、CD4/CD8,以及血清晚期糖基化终末产物(AGEs)、内毒素(EXT)、二胺氧化酶(DAO)水平测得值经比较其差异均无统计学意义(P＞0.05);治疗后观察组的大肠埃希菌菌落数显著少于对照组(P＜0.05),而双歧杆菌、乳杆菌菌落数均显著多于对照组(P＜0.05),血清AGEs、EXT、DAO测得值均低于对照组(P＜0.05),血清IgA、IgG、CD4/CD8测得值均显著高于对照组(P＜0.05).结论:采用双歧杆菌三联活菌散辅助利巴韦林颗粒治疗TVE患儿,有效改善了其肠道菌群、机体免疫力,降低了肠黏膜的通透性,提高了临床疗效.     

双歧三联活菌；肝硬化；肠道菌群；内毒素；肠黏膜屏障功能

摘 要 目的：观察双歧三联活菌辅助治疗对肝硬化患者肠道菌群、血浆内毒素及肠黏膜屏障功能的影响。方法：70例肝硬化患者随机分为对照组和观察组各35例。对照组患者给予对症支持治疗,观察组在对照组基础上加用双歧三联活菌胶囊治疗。疗程均为4周。比较两组患者治疗前后肠道菌群(肠杆菌、肠球菌、双歧杆菌、乳杆菌、酵母样真菌)、血浆内毒素及降钙素原(PCT)、二胺氧化酶(DAO)等肠黏膜屏障功能指标变化。结果：治疗后,观察组肠杆菌、肠球菌、双歧杆菌、乳杆菌等菌落数均明显高于治疗前及对照组治疗后(P<0.05),而酵母样真菌菌落数明显低于治疗前及对照组治疗后(P<0.05)。两组治疗后血浆内毒素及PCT、DAO等表达水平均较治疗前明显下降(P<0.05),且观察组明显低于对照组(P<0.05)。两组患者治疗期间均未出现严重的药品不良反应。结论：双歧三联活菌辅助治疗可促进肝硬化患者肠道菌群恢复,降低血浆内毒素水平,提高肠道黏膜屏障功能,值得临床推广应用。     

双歧杆菌三联活菌胶囊治疗乙型病毒性肝炎肝硬化的临床研究北大核心CSCD

目的观察双歧杆菌三联活菌胶囊治疗乙型病毒性肝炎(乙肝)肝硬化的临床疗效及安全性。方法将366例乙肝肝硬化患者随机分为对照组183例和试验组183例。对照组给予异甘草酸镁注射液和还原型谷胱甘肽等常规治疗;试验组在对照组的基础上,给予双歧杆菌三联活菌胶囊每次400 mg,每天3次,口服。2组患者均治疗4周。比较2组患者的血清指标、肠道菌群情况及药物不良反应发生情况。结果治疗后7 d,试验组双歧杆菌属和乳酸杆菌属分别为(26.06±3.55)%,(22.27±2.97)%,治疗后28 d,试验组乳酸杆菌属和乳酸杆菌属分别为(27.67±3.33)%,(23.94±3.47)%,差异均有统计学意义(均P<0.05)。治疗后28 d,试验组和对照组的二胺氧化酶分别为(19.37±3.55),(22.64±2.97)U·mL^(-1);血浆中内毒素(ET)含量分别为(0.11±0.03),(0.25±0.08)Eu·mL^(-1),白细胞介素-6(IL-6)含量分别为(2.09±0.45),(2.59±0.61)ng·L^(-1);肿瘤坏死因子-α(TNF-α)含量分别为(157.27±40.30),(186.27±40.96)ng·L^(-1),差异均有统计学意义(均P<0.05)。2组患者治疗期间均未发生药物不良反应。结论双歧杆菌三联活菌胶囊治疗乙肝肝硬化的临床疗效较好,其可显著改善患者的肠道菌群情况,降低体内炎症因子水平,且安全性较高。     

双歧杆菌三联活菌胶囊用于腹腔镜胆囊切除术后患者疗效观察

目的:探讨双歧杆菌三联活菌胶囊应用于腹腔镜胆囊切除术后患者的疗效。方法:100例行腹腔镜胆囊切除术患者随机分为观察组与对照组。两组患者均在全麻下行腹腔镜胆囊切除术,术后予常规治疗,观察组在此基础上加用双歧杆菌三联活菌胶囊630 mg,po,bid,疗程1周。观察并比较治疗后两组患者腹泻发生率、肠道菌群失调发生率、血浆D-乳酸的变化情况及药品不良反应。结果:术后1周,观察组患者腹泻及肠道菌群失调发生率均低于对照组(P<0.05);两组患者血浆D-乳酸水平均较治疗前明显降低(P<0.05或0.01),且观察组降低幅度明显大于对照组(P<0.05)。两组药品不良反应发生率比较差异无统计学意义(P>0.05)。结论:双歧杆菌三联活菌胶囊应用于腹腔镜胆囊切除术后患者可有效降低患者血浆D-乳酸水平,减少术后腹泻及肠道菌群失调的发生,安全性较好,有利于患者术后恢复。     

重组溶葡球菌酶治疗小型猪皮肤烫伤MRSA感染*

目的:评价重组溶葡球菌酶对实验性皮肤烫伤耐甲氧西林金葡菌(MRSA)感染的抗感染作用。方法:用中国实验用小型猪建立局部皮肤烫伤后MRSA感染模型,不同处理组创面治疗3 d或7 d后,进行痂下组织活菌计数及组织病理学观察,评价药物抗菌疗效。结果:重组溶葡球菌酶对烫伤皮肤的感染细菌有较好的清除作用,治疗后d 4和d 8高浓度(1 000 U.mL-1)组创面活菌计数[(5.94±0.61)和(4.03±0.75)lg CFU.g-1组织]均明显低于空白对照组[(7.48±0.33)和(6.32±0.60)lg CFU.g-1组织]和阳性药SD-Ag组创面[(7.44±0.19)和(5.29±0.40)lg CFU.g-1组织],P<0.05或P<0.01;治疗后d 8,中浓度(330 U.mL-1)组创面活细菌计数[(5.10±0.29)lg CFU.g-1组织]明显低于空白对照组创面[(6.32±0.60)lg CFU.g-1组织],P<0.05。组织病理学观察也反映了重组溶葡球菌酶的良好疗效。结论:重组溶葡球菌酶对MRSA引起的实验性皮肤烫伤感染有良好的抗感染作用。     

双岐三联活菌对肝硬化患者肠道菌群、血浆内毒素及肝功能的影响

目的本文主要探讨微生态调节剂双歧三联活菌对肝硬化患者肠道菌群、血浆内毒素以及其肝功能的影响。方法将肝硬化失代偿期82例患者随机分为对照组和观察组,每组各41例。对照组予以常规保肝、营养支持、利尿和对症等治疗,实验组在对照组综合治疗的基础上加用双歧三联活菌制剂。观察治疗前后两组患者的肠道菌群菌落计数变化,并对治疗前后各组血浆内毒素、天门冬氨酸转移酶（AST）及丙氨酸氨基转移酶（AIJT）的变化进行比较分析。结果两组患者在实验前肠道菌群、血浆内毒素、肝功能（ALT、AST）比较差异均无统计学意义（P〉0．05）。治疗4周后,对照组患者治疗前后肠道菌群无明显变化（P〉0．05）,实验组患者的肠球菌、双歧杆菌、乳杆菌以及酵母样真菌的菌落数均较治疗前明显增加（P〈0．05）;对照组患者治疗前后血浆内毒素水平无明显变化（P〉0．05）,肝功能AIJ和AST有所降低但不显著（P〉0．05）,实验组患者治疗后血浆内毒素、肝功能（ALT、AST）水平较治疗前明显下降（P〈0．05）。结论口服双歧三联活菌制剂可以促进肝硬化患者肠道正常菌群的恢复、降低血浆内毒素水平,改善其肝功能,安全有效。     

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.     

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.     

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.     

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.     

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.