小鼠菌群失调腹泻模型的建立及超微七味白术散的疗效

【目的】建立菌群失调腹泻的造模方法,研究超微七味白术散对其疗效。【方法】采用抗生素联用、中药复方等不同方法进行腹泻造模,通过超微七味白术散进行治疗。【结果】中药大承气汤能快速致泻,腹泻程度最严重,久灌能出现脾虚症候,但对肠道微生物影响不大(P>0.05)。抗生素联用组中,硫酸庆大霉素和头孢拉定联用组造模效果最好,两者联用,抗菌谱达到最大互补,且混用不使药物失效。经超微七味白术散灌胃治疗后,中药组迅速治愈,脾虚症候消失。抗生素联用组小鼠肠道乳酸菌、真菌数显著高于正常组(P<0.01)。【结论】建立了一种菌群失调腹泻的造模方法,七味白术散中存在促使乳酸菌、真菌生长的益生元。     

中药复方对艰难梭菌毒素基因tcd A/tcd B体外表达的影响

目的探讨中药复方治疗抗生素相关性腹泻(antibiotic associated diarrhea,AAD)的药理机制。方法应用荧光定量PCR技术检测2种中药复方(参苓白术散和理中汤)对2株艰难梭菌临床分离株(A+B+和A-B+)体外培养下毒素基因表达的影响。结果在A+B+艰难梭菌中,参苓白术散组对tcd A和tcd B基因的表达均有显著或是完全抑制,理中汤也有显著的抑制;而对于A-B+艰难梭菌,2种中药复方则完全抑制tcd B基因的表达。结论通过影响毒素基因的表达可能是中药复方治疗AAD的药理学机制之一。     

益气健脾中药颗粒剂对早期断奶仔猪肠道菌群的影响

目的研究中药复方颗粒剂对断奶仔猪肠道微生态的影响。方法实验选用人工感染大肠埃希菌引起腹泻的28日龄断奶仔猪54头,随机平均分为3组,每组3个重复,Ⅰ组抗生素治疗组、Ⅱ组中药复方颗粒剂治疗组、Ⅲ组不用任何药物治疗的空白对照组。分别于用药后第14天时,每组随机抽取1头屠宰,无菌采集空肠,回肠和盲肠内容物,利用平板计数法测定各肠段大肠埃希菌、双歧杆菌和乳酸杆菌数量。结果 Ⅰ组双歧杆菌、乳酸杆菌及大肠埃希菌的数量均显著小于Ⅲ组（P〈0.05）;Ⅱ组双歧杆菌和乳酸杆菌的数量显著大于Ⅲ组（P〈0.05）,大肠埃希菌数量显著小于Ⅲ组（P〈0.05）; n组双歧杆菌和乳酸杆菌的数量极显著大于Ⅰ组（P〈0.01）,Ⅱ组与Ⅰ组大肠埃希菌数量差异无统计学意义（P〉0.05）。结论该中药复方颗粒剂具有显著增加断奶仔猪肠道中双歧杆菌和乳酸杆菌的数量,降低大肠埃希菌数量,减少腹泻频率的作用。     

黄芩汤药效物质基础及其治疗胃肠道疾病研究进展

黄芩汤是《伤寒论》中治疗下痢的经典方剂,由黄芩、芍药、甘草(炙)和大枣四味中药煎煮而成,用于治疗痢疾、腹泻等胃肠道疾病已有近1800年,中药治疗胃肠道疾病相较于西药更安全。本文结合国内外相关文献,对近几年来黄芩汤药效物质基础研究进行概括总结,并对其治疗溃疡性结肠炎和减轻化疗药物胃肠道毒性机制的最新研究进行了综述,结合胃肠道疾病的发病机制以及黄芩汤减毒机制的研究方法对现有研究过程中存在的不足进行了评述,并对中药疗效研究展开设想,提出以组学作为研究手段,配合中药复方整体作用模式的组分-疗效研究思路,以期为黄芩汤治疗胃肠道疾病的研究提供参考。     

微生态制剂在控制艰难梭菌相关腹泻中的应用现状与前景

目的 以艰难梭菌感染为主的抗生素相关腹泻发病率和严重程度在全球范围内呈上升趋势,是一个备受关注的健康问题.本文主要介绍了微生态制剂的性质,以及其在艰难梭菌相关腹泻人群中应用的进展情况和作用机制,同时总结了微生态制剂在治疗和预防艰难梭菌相关腹泻中的生物安全性及其优点,对深入研发、推广使用针对抗生素相关腹泻的微生态制剂具有一定的参考价值.     

婴幼儿抗生素相关性腹泻的影响因素及其防治

目的分析婴幼儿抗生素相关性腹泻的影响因素,观察地衣芽孢杆菌活菌制剂在预防抗生素相关性腹泻中的疗效。方法选择大连医科大学附属二院2016年11月至2017年2月因支气管肺炎应用广谱抗生素治疗的265例婴幼儿患者,随机分成实验组(140例)和对照组(125例)。实验组患儿从应用抗生素治疗第1天开始预防性口服地衣芽孢杆菌(0.25g/次,3次/d)直至停用抗生素;对照组患儿出现腹泻后加用地衣芽孢杆菌治疗,用药至腹泻缓解,剂量和用法与实验组一致。观察两组患儿抗生素相关性腹泻出现的例数,腹泻出现时间,持续时间,大便次数及性状。分析年龄、抗生素应用时间、是否联合应用抗生素与抗生素相关性腹泻之间的关系。结果 (1)年龄小于1岁、应用抗生素时间大于7d和联合应用抗生素均是婴幼儿发生抗生素相关性腹泻的高危因素。(2)预防性使用地衣芽孢杆菌后,实验组患儿腹泻发生率明显低于对照组,腹泻出现时间晚于对照组,腹泻持续时间短于对照组,平均大便次数少于对照组,差异均有统计学意义(P0.05)。结论 (1)婴幼儿长时间应用抗生素和联合应用抗生素易导致抗生素相关性腹泻的发生。(2)预防性应用地衣芽孢杆菌活菌制剂可以有效减轻抗生素相关性腹泻的发生及其严重程度。     

中药复方防治脑缺血的研究进展

脑缺血是危害人类健康的主要疾病之一,其在老年人中发病率较高,且具高死亡率、高致残率和高复发率的特点,给社会和家 庭带来了巨大负担。目前,基于脑缺血损伤的不同机制,针对性开发出多种抗脑缺血药物,但往往疗效不甚理想。而中药复方因其多途径、 多靶点的作用方式,在预防和治疗脑缺血及脑缺血再灌注损伤中有其独特优势,临床应用前景看好。分类综述传统中药复方、现代复方 制剂及临床经验方对脑缺血的治疗作用研究进展。     

呼吸科住院患者抗生素药物相关腹泻发生现状及影响因素分析

目的了解呼吸科住院患者抗生素药物相关腹泻发生现状并探讨相关影响因素。方法选取2019年1月-2019年9月我院呼吸科病房收治使用抗生素治疗的患者为研究对象,采用前瞻性队列研究,收集患者基本资料、抗生素使用情况及相关因素,以探讨抗生素药物相关腹泻的影响因素。结果本研究共纳入291例患者,抗生素药物相关腹泻发生率为11.3%。COX回归显示,入院时便潜血(OR=4.730,P0.001)、BMI(OR=0.918,P=0.027)、入院时血红蛋白水平(OR=0.974,P=0.007)、院前抗生素使用(OR=3.246,P=0.011)、单日使用抗生素最大种类数(OR=2.665,P=0.001)为抗生素药物相关腹泻的影响因素,便潜血阳性患者较阴性患者抗生素药物相关腹泻发生率高,入院时BMI、血红蛋白水平低,住院前已开始使用抗生素,单日抗生素使用种类多的患者抗生素药物相关腹泻发生率高。结论抗生素药物相关腹泻为呼吸科住院患者中常见的并发症,临床上对于便潜血阳性患者、BMI和/或血红蛋白水平较低的患者、住院前已开始使用抗生素的患者、感染较重需联合使用抗生素的患者,应在行抗生素治疗方案前做好抗生素药物相关腹泻的预防工作。     

中药91—4对抗生素相关性腹泻小鼠肠道膜菌群及腔菌群的影响

本实验以肠道菌检测与电镜观察法,初步研究了中药９１－４对抗生素相关性腹泻小鼠肠道菌群的影响。结果表明,盐酸林可霉素对小鼠肠道膜菌群、腔菌群干扰显著、乳酸杆菌、双歧杆菌及肠杆菌等比正常对照组明显减少,致小鼠腹泻或肠炎;中药９１－４能够促进肠道乳酸杆菌、双歧杆菌等生长繁殖,对肠道膜菌群、腔菌群均具有调整作用,加速肠粘膜病变的愈合及修复,可有效地控制ＡＡＤ模型小鼠的腹泻症状。     

七味白术散对抗生素所致腹泻小鼠 肠道乳糖酶活性的影响

目的探讨七味白术散对抗生素所致腹泻小鼠肠道乳糖酶活性的影响,从肠道功能酶角度阐释七味白术散治疗抗生素所致腹泻的作用机制。方法将SPF级昆明小鼠分为正常组、自愈组和治疗组。采用硫酸庆大霉素和头孢拉定混合抗生素制备腹泻小鼠模型,造模成功后,自愈组和正常组给予无菌生理盐水,治疗组灌胃七味白术散,治疗4d。无菌条件下采集治疗前后各组小鼠肠道前、中、后段黏膜,使用ONPG法测定样品中乳糖酶活性。结果抗生素所致腹泻模型小鼠肠道黏膜乳糖酶活性降低,七味白术散治疗4d后,治疗组小鼠腹泻症状消失,肠道黏膜乳糖酶活性恢复且提高。结论抗生素可引起小鼠腹泻及肠道乳糖酶活性下降,七味白术散可促进腹泻小鼠肠道黏膜乳糖酶活性恢复而治疗腹泻。     

基于分子对接技术筛选中草药中潜在的H1N1病毒神经氨酸酶抑制剂

甲型H1N1流感病毒是一种高度接触性急性呼吸道传染病,给人类健康造成了极大威胁。作为一个已经被证明的抗流感药物靶点,神经氨酸酶在流感病毒复制和传播中发挥重要作用,并且其活性中心的氨基酸组成高度保守。本研究中,我们使用分子对接技术筛选从中草药小分子数据库中筛选神经氨酸酶潜在的抑制剂,结果得到4个亲和力高于奥司他韦(Osel-tamivir)的化合物,并确定了他们的中草药来源。为从草药中提取,设计以及实验合成新的神经氨酸酶抑制剂提供了一定的依据和指导。     

中药91－4对抗生素相关性腹泻小鼠肠道膜菌群及腔菌群的影响

本实验以肠道菌群检测与电镜观察法,初步研究了中药９１－４对抗生素相关性腹泻（ＡＡＤ）小鼠肠道菌群的影响。结果表明,盐酸林可霉素对小鼠肠道膜菌群、腔菌群干扰显著,乳酸杆菌、双歧杆菌及肠杆菌等比正常对照组明显减少,致小鼠腹泻或肠炎;中药９１－４能够促进肠道乳酸杆菌、双歧杆菌等生长繁殖,对肠道膜菌群、腔菌群均具有调整作用,加速肠粘膜病变的愈合及修复,可有效地控制ＡＡＤ模型小鼠的腹泻症状。     

中药91—4对抗生素相关性腹泻小鼠肠道膜菌群影响的电镜研究

实验用菌群检查和光、电镜相结合的方法,观察了中药９１—４对抗生素相关性腹泻（ＡＡＤ）小鼠肠道膜菌为及其病理学变化的影响。由林可霉素灌胃致小鼠腹泻模型并证实菌群紊乱后,给各治疗组分别灌喂中药,并设自然恢复组,一个疗程后,时各组小鼠进行肠道膜菌群检测分析,同时取回盲部组织标本,分别用光镜及电镜观察肠粘膜结构。结果表明,ＡＡＤ模型组大多数小鼠肠粘膜出现不同程度的损害,治疗一个疗程后,病理组织学及超微结构改变基本恢复正常。９１－４不仅对肠道膜菌群有调整作用,对肠粘膜也有一定的修复作用。     

A method for the production and characterization of fractionated libraries from Chinese herbal formulas

High-throughput screening (HTS) for pharmaceutical leads requires sufficient number of samples with vast chemical diversity. In this paper, we proposed Chinese herbal formulas as an attractive source for HTS and introduced a strategy for the production of high-quality fractionated libraries. An offline two-dimension liquid chromatography protocol was developed to separate medium- and low-polar extract (MLPE) of Chinese herbal formulas, which implemented the production of semi-purified mixture libraries. HPLC coupled with diode-array detector (DAD) and mass spectrum (MS) analysis was performed to obtain MS and UV spectrum of library components. The detected components were characterized by retention, molecular weight and UV absorbance assisted by WiseProcessor, a customer-developed software to automatically process analytical data. Based on the current understanding in pathophysiology and pharmacology, multiple cell-based bioassays were performed to screening the library samples. Through validation and dereplication process, bioactive compounds could be identified rapidly. The combination of off-line two-dimension liquid chromatography separation, HPLC-DAD-MS analysis and computer-aided data processing is reliable and efficient for the utilization of Chinese herbal formulas as valuable sources for HTS. As a demonstration, a library sample set was generated from Qi-Xue-Bing-Zhi Formula, an efficient Chinese herbal formula to treat atherosclerosis. Several bioactive compounds were quickly identified from this library through the screening and dereplication process.     

The role of D-dimers in the diagnosis of acute aortic dissection

Acute aortic dissection (AAD) is a life threatening cardiovascular medical emergency with a poor prognosis. To explore the utility of D-dimers (DD) in the diagnosis of AAD, we performed a prospective study and conducted a meta-analysis of previous studies. 368 suspected patients were enrolled, including AAD n = 89, PE n = 12, AMI n = 167, normal controls n = 100. All patients had a DD test immediately after admission. We then performed a comprehensive computer search to identify studies investigating using DD as a screening tool for AAD. Finally, we pooled these data to estimate sensitivity, specificity, positive and negative likelihood ratios (LRs) by using DerSimonian–Laird random-effects models. The DD concentrations in the AAD group were significantly higher than those in the AMI and normal control groups. However, the DD level of 500 ng/ml had a poor sensitivity of 51.7 % and specificity of 89.2 % in the diagnosis of AAD. Subgroup analyses found that DD only showed a well discriminative ability of distinguishing AAD patients from normal controls (specificity and positive LR was 97 % and 17.2, respectively). The pooled sensitivity, specificity, positive and negative LR in our meta-analysis was 89, 68 %, 2.71, 0.07, respectively. In conclusion, our results suggest that plasma DD levels cannot add to the certainty of AAD diagnosis and it is not a good biomarker for AAD. In the future, prospective research on patients from many parts of the world is warranted to validate our findings. In addition, different controls, methods of plasma DD assays and other factors should be considered.     

中草药干预糖尿病肾病炎症的作用

随着糖尿病发病率逐年升高,糖尿病肾病成为导致慢性肾脏疾病和终末期肾脏疾病的主要原因。而目前控制血糖及抑制肾素-血管紧张素系统的药物治疗,并不能有效防止糖尿病肾病进展。近年来发现,慢性低水平炎症和免疫系统激活在糖尿病性肾病的发生及发展中起着至关重要的作用。明确糖尿病肾病进展中的炎症机制将有助于确定新的潜在靶点及研发抗炎治疗策略。越来越多的证据表明,中药治疗可以有效改善糖尿病性肾病的高血糖和蛋白尿,并能延缓其进展成为终末期肾病。糖尿病肾病动物实验和体外研究证实中药复方、中草药提取物和中药单体具有调节炎症介质的作用。本文旨在归纳总结文献中与糖尿病肾病肾损伤相关的炎症分子和途径,并探讨中草药靶向抗炎治疗糖尿病肾病的作用。     

Pathway as a Pharmacological Target for Herbal Medicines: An Investigation from Reduning Injection

As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.     

Second-generation antimalarial endoperoxides

Artemisinin, derived from a Chinese herbal remedy, is a potent peroxide-containing antimalarial. New types of peroxides, derived from this structure, as well as other naturally occurring antimalarial peroxides, have been synthesized and found to have potent antimalarial activities. Studies on the activities, modes of action, and toxicities of these compounds are discussed here by Steven Meshnick and colleagues.     

Study on Antibiotic Constituents of Nanclea officinalis Pierre ex Pitard

Nauclea officinalis pierre ex Pitard is a Chinese traditional and herbal drug for antibiotics and anti-inflammation. Four compounds have been isolated from it and identified as naucleidinal, quinovaic acid, β-sitosterol and alkaloid C20H14N202. Two alkaloids have inhibiting effect on bacteria. The structure of C20H14N202 will be identified later.