基于网络药理学的中药组方“芩部丹”治疗肺结核作用机制研究

目的: 运用网络药理学方法探索中药组方“芩部丹”治疗肺结核的作用机制。方法: 运用中药系统药理学数据库与分析平台(TCMSP)检索黄芩、百部及丹参的药物活性成分及潜在靶点。结合GeneCards、OMIM、TTD及DrugBank数据库搜索肺结核的相关基因靶点。基于Uniprot数据平台对靶点的基因名称进行整理与规范,在STRING 11.0数据平台上生成“芩部丹”治疗肺结核的靶点蛋白互作网络,利用DAVID 6.8平台对靶点进行功能富集与通路分析,利用Cytoscape 3.7.1软件对“芩部丹”治疗肺结核的成分、作用靶点、信号通路进行分析与网络构建。结果: 最终筛选到的“芩部丹”有效化学成分共计116个,作用靶点含有199个。“芩部丹”治疗肺结核的核心活性成分有木犀草素、汉黄芩素、黄芩素、刺槐素、刺芒柄花素、β-谷甾醇、7-甲氧基-3-甲基-2,5-二羟基-9,10-二氢菲,涉及到潜在靶点82个,关键的作用靶点有TP53、IL6、AKT1、VEGFA、EGFR、PTGS2、JUN、CASP3、STAT3、TNF。GO功能富集分析得到生物学过程373条,分子功能66条,细胞组分39条;KEGG通路富集分析获得108条信号通路,关系最密切的为TNF信号通路和细胞凋亡(P值均<0.001),其余包括T细胞受体信号通路、PI3K-Akt信号通路及结核病(P值均<0.001)。结论: 基于网络药理学解释了中药组方“芩部丹”多成分、多靶点、多通路的肺结核治疗机制,为后期的临床与基础研究提供了一定的理论支持。     

肠道菌群失调与肝细胞癌*

大量研究表明,肝病,特别是肝硬化和肝癌患者,发生肠道菌群紊乱或细菌过度生长的机率增高,并且肠道菌群失调与肝细胞癌的发生、发展有着密切的联系;肠道菌群所产生的脂多糖（LPS）可与其识别受体Toll样受体4（TLR4）结合,通过细胞内信号转导通路介导一系列免疫炎症反应,进一步加重肝损伤,促进炎症相关的肝细胞癌发生;抗生素可通过调节肠道菌群,减少内毒素的产生等作用有可能减缓肝细胞癌的发生和发展。     

“动物法则”在烈性传染病防治药物和生物制品开发中的应用

介绍了“动物法则”的产生背景和内容,以及美国FDA根据“动物法则”进行炭疽等不能在人体进行临床试验的疾病防治药物和生物制品审批时的相关要求。从产品特性、动物有效性实验结果及使用时的注意事项等方面对近年来美国食品药品监督管理局根据“动物法则”批准上市的一些产品进行简述。综述表明,“动物法则”对产品开发者提出严格要求的同时,建议开发者在开发前后的一系列过程中都要时刻保持与FDA的密切交流,设计研发出解决实际问题的产品。     

新疆包虫病“医防结合”模式的建立及初步应用实践

目的 建立包虫病“医防结合”创新诊疗新模式,并将此模式应用推广。方法 选取新疆5个县级包虫病定点医院作为试点县,初步实施“医防结合”创新诊疗新模式。以伊犁州察布查尔县为例,探讨此模式初步实施效果。评估指标包括包虫病病人登记管理率、免费包虫病药品使用率、病人规范治疗率、随访督促服药率,治疗后的患者疗效得到科学评估。结果 梳理伊犁州察布查尔县人民医院2016年6月至2019年12月的包虫病患者救治情况,手术后服药患者137人,其中治愈患者109人,治愈率达79.6%;无手术指征药物治疗患者59人,治愈率16.9%,有效率59.3%。失访患者10人,病人规范治疗率94.9%;随访督促服药率94.9%。结论 实践证明,包虫病“医防结合”诊疗新模式的建立,在一定程度上规范了包虫病患者服药诊疗流程,可将此模式推广至其他县级包虫病定点医院。     

基于16S rDNA高通量测序研究肠道菌群与抗结核药物性肝损伤的相关性

目的 探讨初治肺结核患者抗结核治疗前后肠道菌群的差异及出现药物性肝损伤时肠道菌群的变化，分析肠道菌群与抗结核药物性肝损伤(ATLI)的相关性。方法 收集2020年1月至2021年1月在苏州市第五人民医院确诊的初治肺结核患者抗结核治疗前后的粪便标本，并根据患者接受抗结核药物治疗4周内是否发生肝功能异常分为肝损组(ATLI组)与对照组(Non-ATLI组),采集发生肝损伤时的粪便标本。利用实验室生化分析仪检测肝功能相关指标；通过细菌16S rDNA高通量测序法比较抗结核前后肠道菌群的多样性、物种组成及组件丰度的变化情况，采用Spearman相关系数分析差异的肠道菌属与血清肝功能指标的关系。结果 两组患者抗结核治疗前后肠道菌群的丰富度，菌群组成及相对丰度差异均具有统计学意义(P<0.05);两组患者抗结核治疗前后，肠道菌群的结构均发生了改变(P<0.05);通过LEfSe分析，两组患者之间共找到17个具有显著差异的分类群(P<0.05);进一步分析肠道差异菌与肝功能指标的关系，发现乳杆菌(Lactobacillus)、Herbinix、Anaerosporobacter、[...     

2009—2020年合肥市肺结核空间特征分析

目的: 分析2009—2020年合肥市肺结核疫情特征及空间聚集性。方法: 通过收集“中国疾病预防控制信息系统”的子系统“结核病管理信息系统”中合肥市2009—2020年肺结核数据,筛选出肺结核患者42681例,利用GeoDa和Arcgis 10.8空间分析软件进行分析,在街道/乡镇水平上绘制空间分布地图,探索空间分布规律及肺结核发病冷热点地区。结果: 2009—2020年合肥市肺结核共报告42681例,报告发病率从2009年57.96/10万(4195/7237966)下降到2020年31.04/10万(2908/9369881),整体呈现波动下降趋势($\chi _{趋势}^{2}$=12.531,P<0.001);全局空间自相关结果显示2009—2014年合肥市肺结核发病呈现空间自相关性(Moran’s I值均>0,P值均<0.05);2015—2020年空间分布偏向随机性。局部自相关分析显示高-高聚集发病街道/乡镇主要集中在长丰县、肥东县;低-低聚集区主要集中在老城区(庐阳区、包河区)。冷热点分析发现,热点区域有2个,分布在长丰县义井乡和肥西县严店乡。结论: 合肥市肺结核疫情存在一定的聚集性,后续应针对不同的县(区)街道/乡镇特点采取不同的防控措施,加大高-高聚集区的街道和热点区域的防控力度。     

肠道菌群失调与肝细胞癌

大量研究表明,肝病,特别是肝硬化和肝癌患者,发生肠道菌群紊乱或细菌过度生长的机率增高,并且肠道菌群失调与肝细胞癌的发生、发展有着密切的联系;肠道菌群所产生的脂多糖(LPS)可与其识别受体Toll样受体4(TLR4)结合,通过细胞内信号转导通路介导一系列免疫炎症反应,进一步加重肝损伤,促进炎症相关的肝细胞癌发生;抗生素可通过调节肠道菌群,减少内毒素的产生等作用有可能减缓肝细胞癌的发生和发展。     

miRNA调节炎症性肠病肠道稳态的研究进展

肠道菌群是调控肠道微小RNA(miRNA)生成的关键因素之一,且miRNA可正向或负向调节肠道免疫和肠道屏障功能,因此肠道菌群可通过miRNA与宿主的相互作用来维持肠道稳态。炎症性肠病患者存在肠道菌群紊乱和异常的miRNA表达,使miRNA成为治疗炎症性肠病的新靶点。     

肝叶切除加“T”管引流术与胆总管空肠Roux-en-Y吻合术治疗肝内胆管结石临床对比研究*

目的探讨肝叶切除加“T”管引流术与胆总管空肠Roux-en-Y吻合术治疗肝内胆管结石的临床效果,评价手术的优越性。方法选择我院2011年1月至2015年1月收治的80例肝内胆管结石患者,采用随机数字表法分为肝叶切除加“T”管引流术组和胆总管空肠Roux-en-Y吻合术组,比较两组患者近期并发症、远期并发症和肝功能指标。结果39例肝叶切除患者术后早期出现残留结石7例（18.0%）、切口感染4例（10.3%）、腹腔感染6例（15.4%）、胆漏4例（10.3%）,而41例空肠Roux-en-Y吻合患者则分别为8例（19.5%,P>0.05）、5例（12.2%,P>0.05）、6例（14.6%,P>0.05）、4例（9.8%,P>0.05）;肝叶切除患者术后出现残胆管炎（8.3%）、结石复发（4.2%）、结石合并胆管炎（4.2%）、吻合口狭窄（4.2%）的比较明显低于空肠Roux-en-Y吻合患者（分别为24.4%、19.5%、7.3%、22.0%,P<0.05）;治疗后,肝叶切除患者血清TBIL为（10.87±2.36）μmol/L、ALT为（38.96±10.28） U/L、AST为（34.76±5.47） U/L、ALP为（108.04±23.40） U/L,而空肠Roux-en-Y吻合患者则分别为（18.96±2.01）μmol/L、（76.83±15.67） U/L、（45.54±4.58） U/L、（176.42±34.58） U/L（P<0.05）。结论肝叶切除加“T”管引流术治疗肝内胆管结石患者疗效显著,远期并发症发生率较低。     

肺结核与肠道菌群相关性的研究进展

随着微生物检测技术的发展,研究发现肠道菌群与人类疾病存在着密切的关系。目前已经有多项研究表明肺结核患者肠道菌群失调,而且机体肠道菌群失调可能会明显地增加肺结核的患病率,两者之间通过菌群代谢和机体的免疫反应等直接或间接地相互影响。作者对肺结核与肠道菌群的关联、两者之间作用的可能机制,以及是否可以通过调节肠道菌群预防和辅助治疗肺结核进行综述。     

支链氨基酸与心血管疾病的关系及干预措施研究进展

大量研究证实支链氨基酸（branched-chain amino acids,BCAAs）在心血管疾病如冠心病、动脉粥样硬化、高血压等的发生和发展中起着重要作用,且宿主BCAAs水平的升高与饮食、肠道菌群、疾病和遗传等因素均密切相关。从因果关系上看,肠道菌群紊乱促进了心血管疾病的发生发展,且部分肠道微生物参与BCAAs的生物合成,直接影响宿主外周BCAAs水平。近年来,从宿主和肠道菌群的角度干预BCAA代谢已成为国内外防治心血管疾病的研究热点。现就BCAAs与心血管疾病关系和肠道菌群-BCAAs代谢途径干预方法的研究进展进行综述。     

Gut microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain–gut–microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.     

益生菌对大肠癌的防治作用及机制研究进展

大肠癌(colorectal cancer,CRC)是目前最常见的恶性肿瘤之一,CRC的发生及发展与肠道微生态有密切的关系。肠道菌群对于肠道功能的维持及内环境的平衡具有重要作用。肠道菌群失调可通过多种途径促进CRC的发生。益生菌是调节肠道微生态的主要方法,并可通过多种机制发挥抗肿瘤作用。本文综合目前研究进展,从调节肠道代谢产物、保护肠道黏膜屏障完整性、抑制肠道炎症、调节宿主免疫反应、促进凋亡和细胞分化、抑制细胞增殖等方面总结益生菌对癌前病变及CRC的防治作用及机制,为临床肠道微生态的调节及CRC的防治提供指导。     

结核病患者白细胞减少原因分析及治疗观察

目的分析结核病患者周围血液白细胞减少原因,探讨防治措施。方法观察肺结核患者抗结核治疗前后血液白细胞总数变化,对其中156例出现血液白细胞减低患者抗结核治疗以前用药情况、造血功能、免疫功能及抗结核药物治疗因素等进行分析,根据不同病因给予相应治疗。结果156例白细胞减低结核病患者中结核感染所致17例,占10.8%,抗结核治疗前及治疗过程中应用非抗结核性药物38例,占24.3%,其中头孢类抗生素为主;抗结核药物(包括喹诺酮类)67例,占42.9%;免疫功能异常19例,占12.2%;其他如放射检查治疗15例,占9.6%,分别给予积极抗结核治疗;停用相应导致白细胞减少药物;尽量减少放射检查等。结论结核病患者白细胞减少原因不同,给予相应措施预防及治疗可取得满意结果。     

Gut microbiota in non‐alcoholic fatty liver disease and alcohol‐related liver disease: Current concepts and perspectives

The term, gut–liver axis, is used to highlight the close anatomical and functional relationship between the intestine and the liver. It has been increasingly recognized that the gut–liver axis plays an essential role in the development and progression of liver disease. In particular, in non‐alcoholic fatty liver disease and alcohol‐related liver disease, the two most common causes of chronic liver disease, a dysbiotic gut microbiota can influence intestinal permeability, allowing some pathogens or bacteria‐derived factors from the gut reaching the liver through the enterohepatic circulation contributing to liver injury, steatohepatitis, and fibrosis progression. Pathways involved are multiple, including changes in bile acid metabolism, intestinal ethanol production, generation of short‐chain fatty acids, and other by‐products. Bile acids act through dedicated bile acid receptors, farnesoid X receptor and TGR5, in both the ileum and the liver, influencing lipid metabolism, inflammation, and fibrogenesis. Currently, both non‐alcoholic fatty liver disease and alcohol‐related liver disease lack effective therapies, and therapeutic targeting of gut microbiota and bile acids enterohepatic circulation holds promise. In this review, we summarize current knowledge about the role of gut microbiota in the pathogenesis of non‐alcoholic fatty liver disease and alcohol‐related liver disease, as well as the relevance of microbiota or bile acid‐based approaches in the management of those liver diseases.     

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem—based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic‐associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.     

165例耐多药肺结核病人治疗前后耐药谱的变化分析

目的了解耐多药肺结核病人在抗结核治疗过程中的耐药状况及其变化趋势。方法对确诊的165例耐多药肺结核病人的耐药菌株,进行治疗前、后药敏结果的比较和分析,并统计治疗前后耐药菌谱变化情况。结果165例耐多药肺结核病人的耐药菌株在治疗前、后对抗结核药物的耐单药例数是有变化的,以乙胺丁醇（ethambutol,EMB）、力克肺疾（pasiniazid,PSNZ）、左氧氟沙星（1evofloxacin,LVFX）三种药物的耐药例数改变明显,获得耐药性增加;对丁胺卡那霉素（amikacin,AMK）、卷曲霉素（capreomycin,CPM）、对氨基水杨酸（sodium aminosalicylate,PAS）三种药物的初始耐药率和获得耐药率较低、复敏率较高。结论对耐多药肺结核病人的耐药菌株,适时监测其耐药谱,获取更新更全面的药敏资料,是有较大意义的;建议治疗耐多药方案中可推广使用AMK、CPM、PAS;同时对目前以LVFX、EMB、PSNZ为主要组成的耐多药方案提出了警示和挑战,尽快开发新一代的低毒高效的抗结核药物是解决目前抗结核治疗困境的当务之急。     

A new strategy of enteral nutrition intervention for ICU patients targeting intestinal flora

Background:Enteral nutrition (EN) therapy is a routine supportive method for patients in the intensive care unit (ICU). However, the incidence of EN intolerance is prevalent, because most ICU patients suffer intestinal mucosal barrier damage and gastrointestinal motility disorder. There is no definite index to predict EN intolerance, and the current treatment methods are not effective in alleviating EN intolerance. Gut microbiota is an important component of the intestinal micro-ecological environment, and alterations in its structure and composition can reflect changes in intestinal function and microenvironment. The purpose of this study is to investigate the effect of EN on the gut microbiota of ICU patients by monitoring the dynamic alterations of gut microbiota and to screen out the microbial markers that can be used to predict the incidence of EN intolerance.Methods:One hundred ICU patients with trauma or in a period of acute stress after surgery will be enrolled, and their fecal samples will be collected at different timepoints for microbial sequencing and analysis. General clinical data (demographic information, surgical data, laboratory parameters, illness severity scores, and therapeutic drugs), nutritional status data (nutritional status assessment and nutrition therapy monitoring data), as well as clinical outcomes, will be recorded. The microbial and clinical data will be combined to analyze the baseline characteristics and dynamic alterations of gut microbiota along with the incidence of EN intolerance. Data related to the gut microbiota will be statistically analyzed by R software, and other data performed by SPSS23.0 software.Conclusions:The effect of EN on gut microbiota and microbial markers predicting the intolerance of EN will lead us to develop a new nutrition intervention strategy for ICU patients. Furthermore, the results of this study will provide a basis for the discovery of potential probiotics used for the prevention and treatment of EN intolerance.     

Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring

From birth to adulthood, the gut microbiota matures from a simple community dominated by a few major bacterial groups into a highly diverse ecosystem that provides both benefits and challenges to the host. Currently there is great interest in identifying environmental and host factors that shape the development of our gut microbiota. Breast milk is a rich source of maternal antibodies, which provide the first source of adaptive immunity in the newborn's intestinal tract. In this addendum, we summarize our recent data demonstrating that maternal antibodies in breast milk promote long-term intestinal homeostasis in suckling mice by regulating the gut microbiota and host gene expression. We also discuss important unanswered questions, future directions for research in this field, and implications for human health and disease.     

Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring

From birth to adulthood, the gut microbiota matures from a simple community dominated by a few major bacterial groups into a highly diverse ecosystem that provides both benefits and challenges to the host. Currently there is great interest in identifying environmental and host factors that shape the development of our gut microbiota. Breast milk is a rich source of maternal antibodies, which provide the first source of adaptive immunity in the newborn''s intestinal tract. In this addendum, we summarize our recent data demonstrating that maternal antibodies in breast milk promote long-term intestinal homeostasis in suckling mice by regulating the gut microbiota and host gene expression. We also discuss important unanswered questions, future directions for research in this field, and implications for human health and disease.