肠道微生物群-TLR4-肝轴参与肝细胞癌的发生发展

肝癌是大多数慢性肝病终末期的表现(如:肝炎、肝硬化等),其发生是基因突变、环境改变、病毒影响等多因素共同作用的结果,经历多阶段发展的结果.肝癌最常见的类型是肝细胞癌(hepatocellular carcinoma,HCC),且HCC的死亡率高、术后复发率居高不下成为了全球第三大死因.大量的研究表明,肠道微生物群-TL...     

肠道菌群失调与肠易激综合征的研究进展

肠易激综合征（IBS）的发病机制复杂,可能与内脏感觉过敏、胃肠道动力异常、肠道菌群失调、小肠细菌过度生长、肠道感染、食物不耐受、免疫异常、社会心理因素以及脑一肠轴异常等有关。研究显示,肠道菌群失调可能与IBS症状的产生和持续有关。本文就肠道菌群失调与IBS的研究进展作一综述。     

Toll样受体4在肝细胞癌发展中的作用

正肝细胞癌(hepatocellular carcinoma,HCC)是常见的消化系统恶性肿瘤,其发病率及死亡率均较高。肝硬化、病毒感染、非酒精性脂肪性肝病、酒精性肝病、黄曲霉毒素等是HCC常见的病因。据推测,病毒因子的入侵和宿主免疫系统的紊乱是诱导HCC的主要危险因素~([1])。HCC的治疗十分棘手,预后也较差,无法手术切除的病变,对化疗药物具有     

NAFLD与肝细胞癌的相关性研究进展*

非酒精性脂肪性肝病（NAFLD）已成为世界范围内最常见的慢性肝脏疾病,被认为是代谢综合征在肝脏的表现,其疾病谱从轻微肝细胞脂肪变性到非酒精性脂肪性肝炎（NASH）,进一步可发展为肝硬化或肝细胞癌（HCC）。随着肥胖及胰岛素抵抗问题的日益严重,NAFLD、NASH及其相关肝硬化、肝癌患者也日益增多。近年来研究表明,NASH可不经肝硬化阶段直接发展为HCC,具体机制尚不明确。     

肝细胞癌患者PBMCs TLR 2/4表达和小肠细菌过度生长对TACE术后生存期的影响

目的 探讨肝细胞癌(HCC)患者外周血单个核细胞(PBMCs)表面Toll样受体2(TLR2)和TLR4表达及小肠细菌过度生长(SIBO)对经肝动脉化疗栓塞(TACE)术后生存期的影响.方法 2013年1月 ～2016年6月我院诊治的47例HCC患者和同期在本院体检的100例健康人,所有患者接受TACE治疗.使用Cyt...     

肠道菌群与肝细胞癌关系的研究进展

肠道和肝脏在解剖学和生理学上是相互连接的,并且这种"肠-肝轴"对肝脏病理学产生各种影响.随着对该轴研究的进一步深入,通过改善肠道菌群已成为预防性治疗肝细胞癌(hepatocellular carcinoma,HCC)的一个新前沿.肠道渗漏和营养不良通过多种机制促进肝病的进展和HCC的发展,探讨肠道菌群与HCC之间的关系...     

小肠细菌过度生长与胰腺疾病

小肠细菌过度生长(SIBO)指小肠内细菌数量和种类发生改变并引起消化吸收障碍等病理生理异常的综合征。SIBO在胰腺疾病中发病率较高, 可影响胰腺疾病病理生理过程。本文就SIBO与AP、CP、胰腺癌关系进行综述。     

肝硬化发生发展中肠道微环境的变化

肠道微环境主要是指肠道菌群及其代谢产物与机体相互作用后所形成的一个相对稳定的共生环境.肝硬化是肝脏慢性进行性损害的终末期表现,在肝硬化发生发展过程中会伴随肠道微环境改变.肠道内的双歧杆菌与拟杆菌等优势菌群数量减少,革兰氏阴性肠杆菌、肠球菌等增加,随之发生的小肠菌群过度生长与肠道菌群移位在肝硬化进展期非常普遍.与此同时,肠道菌群失衡也会对肝脏产生影响,使肝功能受损,促发肝硬化并发症.我们对近年来肝硬化中肠道微环境变化的研究进展作一综述.     

肝细胞癌患者癌组织miRNA-30c水平变化及其临床意义探讨*

目的 探讨肝细胞癌（HCC）患者癌组织微小RNA（miRNA）-30c（miRNA-30c）水平变化及其与预后的关系。方法 2010年2月~2012年11月我院收治的HCC患者35例,经外科手术切除肿瘤获得癌组织标本。采用RT-PCR法检测癌组织miRNA-30c相对水平。不同临床和病理因素患者癌组织miRNA-30c水平高低的风险比（OR）和95%可信区间（CI）采用Logistic二项回归分析。采用Kaplan-Meier最小乘积法评价患者的生存率,不同miRNA-30c水平患者生存率的差异比较采用Log-Rank检验。结果 35例HCC患者癌组织miRNA-30c相对水平为0.6,95%CI为0.3~0.6,其中癌组织miRNA-30c相对水平低于0.6者13例,大于0.6者22例;不同性别、年龄、肿瘤大小、分化程度、TNM分期、有无肝炎病史和血清甲胎蛋白（AFP）水平高低患者癌组织miRNA-30c水平差异无统计学意义（P>0.05）,但17例存在淋巴结转移患者癌组织miRNA-30c水平为（0.2±0.0）,显著低于18例无淋巴结转移患者【（0.8±0.1）,P<0.05】;调整后的风险比（OR）=5.4,95%CI：1.2~20.1;癌组织miRNA-30c高水平患者总生存期为（14.5±6.7）个月,95%CI为11.0~28.4个月,显著长于低水平患者【（7.9±1.5）个月,95%CI为3.2~10.7个月,P<0.05】。结论 本研究结果表明,HCC患者癌组织miRNA-30c相对水平与患者预后有关,其是否可作为潜在的PLC诊断和预后判断的生物学标志物还需进一步研究。     

Intestinal permeability and bacterial growth of the small bowel in patients with primary sclerosing cholangitis

Objective. Animal studies show that small intestinal bacterial overgrowth and infusion of bacterial antigens into portal blood cause hepatic histological changes similar to those seen in primary sclerosing cholangitis in man. It has been suggested that a similar mechanism involving bacterial overgrowth with increased small-bowel permeability may play a pathogenic role in patients with primary sclerosing cholangitis.Material and methods. Twenty-two patients with primary sclerosing cholangitis (13 M, 9 F, median age 37 years, range 21–74 years), 19 of whom (83%) had quiescent inflammatory bowel disease, were included in the study along with 18 healthy volunteers (9 F, 9 M, median age 36 years, range 23–80 years). Small-bowel bacterial overgrowth was defined as the presence of colonic flora >10⁵ colony-forming units (cfu)/ml from duodenal aspirations. Small-bowel intestinal permeability was assessed as the differential urinary excretion of lactulose/L-rhamnose.Results. Bacterial overgrowth was evident in one patient with primary sclerosing cholangitis (4.5%) (Enterobacter) and in none of the controls. Intestinal permeability in patients with primary sclerosing cholangitis (0.034 (0.026–0.041) (median, interquartile range (IQR)) did not differ significantly from that of the controls (0.033 (0.025–0.041).Conclusions. Small intestinal bacterial overgrowth and increased intestinal permeability does not seem to play an important pathogenic role in patients with primary sclerosing cholangitis.     

A Case of Nonalcoholic Steatohepatitis and Small Intestinal Bacterial Overgrowth with Peripheral Edema Caused by Intestinal Bypass Surgery and Relieved by Repair

Intestinal bypass surgery, particularly jejuno-ileal bypass surgery, performed for the purpose of weight reduction may cause an unexpected exacerbation of nonalcoholic steatohepatitis (NASH). Here, we report a case of NASH caused by small intestinal bacterial overgrowth, which developed after jejuno-colic bypass surgery and resolved dramatically after surgical correction.     

肝硬化患者小肠细菌过度生长及其外周血单个核细胞TLR4表达的变化

目的探讨肝硬化患者小肠细菌过度生长（SIBO）和外周血单个核细胞表面TLR4表达的变化。方法采用乳果糖-氢呼气试验（LHBT）检测40例肝硬化患者和16例正常人小肠细菌生长情况,使用流式细胞仪检测外周血单个核细胞表面TLR4表达。结果肝硬化患者SIBO检出率为42.5%（17/40）,显著高于正常人的6.3%（1/16,P<0.01）;肝硬化患者外周血单个核细胞表面TLR4相对表达量为（23.4±11.4）,显著高于正常人的【（14.4±5.2）,P<0.05】;17例肝硬化SIBO阳性患者外周血单个核细胞表面TLR4表达为（30.2±12.3）,显著高于23例肝硬化SIBO阴性患者【（19±8.6）,P<0.05】。结论肝硬化患者存在较高的SIBO发生率,外周血单个核细胞表面TLR4表达上调,SIBO可能通过与TLR4的作用在肝硬化病情进展中发挥作用。     

小肠细菌过度生长与肝硬化并发自发性腹膜炎

目的探讨小肠细菌过度生长(SIBO)与肝硬化并发自发性腹膜炎(SBP)之间的关系,方法对80例肝硬化患者的SIDO和并发SBP情况进行分析,并与健康对照组进行比较。结果 80例肝硬化患者中27例SIBO阳性,阳性率33.75%(27/80),按Child-Pugh分级分组,分为A级、B级、C级三组,其SIBO阳性率分别为14.8%(4/27)、29.6%(8/27)、57.7%(15/26),各组间比较差异有显著性(P<0.01)。健康对照组25例SIBO全为阴性,与肝硬化组比较差异有显著性(P<0.01)。58例肝硬化并发SBP患者中有25例SIBO阳性,阳性率为43.1%;22例未并发SBP患者2例存在SIBO阳性,阳性率为9.1%,两组比较有统计学差异(P<0.01)。肝硬化并发SBP且SIBO阳性的25例患者,经2周治疗后有20例SIBO转阴,其中并发SBP的有2例,而在治疗后SIBO仍然阳性的5例患者中,并发SBP者有4例。结论肝硬化患者SIBO发生率高,并且随着肝功能损害程度的加重,SIBO发生率也随之增加,肝硬化伴SBP者SIBO发生率增加尤为显著。治疗SIBO能显著减少SBP的发生率。     

肝硬化患者小肠细菌过度生长在肠道气体产生中的作用

肝硬化是我国常见疾病和主要死亡原因之一,肝硬化患者由于门静脉高压致胃肠道瘀血、胆汁酸和胃酸的相对缺乏、肠道运动障碍等因素,可导致肠腔需氧菌增多,结肠的细菌移行至空肠和十二指肠,引起小肠细菌过度生长(small intestinal bacterial overgrowth,SIBO),继而增加内源性感染的机会[1].在临床中发现,肝硬化患者常伴有肠道气体增多,并导致肠胀气、腹胀、腹痛等症状,影响患者生活质量及增加临床治疗难度,目前肝硬化小肠细菌过度生长与肝性脑病、内毒素血症的关系研究较多[2-3],但有关肝硬化小肠细菌过度生长与肠道气体形成的研究较少.本研究通过观察肝硬化伴小肠细菌过度生长患者经过微生态制剂治疗后肠道气体的变化,旨在探讨小肠细菌过度生长在肝硬化患者肠道气体产生中的作用,希望为肝硬化患者肠道气体的治疗提供新的方向.     

A Systematic Review of Diagnostic Tests for Small Intestinal Bacterial Overgrowth

Background A growing number of studies seem to suggest that small intestinal bacterial overgrowth (SIBO) is a common clinical problem. Although various techniques are available to make this diagnosis, tradition has accepted small bowel aspirate (>10⁵ cfu/ml) as a gold standard. In this systematic review, the validity of culture and other diagnostic testing for SIBO is evaluated. Methods We performed a systematic review of the literature from 1966 to present using electronic databases (PubMed and OVID). Full paper review of those abstracts that fulfilled preset criteria was carried out to evaluate the validity of various tests in diagnosing SIBO. Finally, all papers were evaluated against published standards for studies on diagnostic testing. Results Seventy-one papers met the criteria for detailed review. Studies were very heterogeneous with regards to patient populations, test definitions, sample size, and methods in general. Small bowel colony counts appeared elevated in most gastrointestinal diseases compared to controls. The traditional definition of >10⁵ cfu/ml was usually indicative of stagnant loop conditions. Although, numerous diagnostic tests were studied, not even culture papers met the quality standards described by Reid et al. Breath testing and other diagnostic testing suffered therefore from the lack of a gold standard against which to validate in addition to the poor quality. Conclusions There is no validated diagnostic test or gold standard for SIBO. In this context, the most practical method to evaluate SIBO in studies at this time would be a test, treat, and outcome technique.     

肝硬化患者小肠细菌过度生长与轻微肝性脑病的相关性研究

目的探讨肝硬化患者小肠细菌过度生长与轻微肝性脑病(MHE)的相关性。方法60例肝硬化患者(肝硬化组)及20名健康志愿者(对照组)全部接受葡萄糖氢呼气试验检测小肠细菌过度生长情况,进行数字连接试验(NCT-A及NCT-BC)和数字符号试验诊断MHE。抗生素抑制小肠细菌过度生长后再进行以上试验,对比治疗前后观察指标的变化。结果对照组检出1例患者(5%)伴小肠细菌过度生长,未检出MHE。肝硬化组共检出20例(33.3%)患者伴小肠细菌过度生长,MHE 26例(43.3%),其中伴小肠细菌过度生长肝硬化患者MHE检出17例,不伴小肠细菌过度生长患者MHE检出9例。应用抗生素抑制小肠细菌过度生长1周后20例小肠细菌过度生长患者有18例葡萄糖氢呼气试验阴性,17例伴小肠细菌过度生长的MHE患者13例数字连接试验和数字符号试验正常。肝硬化患者小肠细菌过度生长与MHE存在相关性,相关系数为0.511(P<0.005)。结论部分肝硬化患者存在小肠细菌过度生长,伴小肠细菌过度生长肝硬化患者的MHE检出率高于不伴小肠细菌过度生长肝硬化患者,应用抗生素抑制小肠细菌过度生长后MHE检出率明显下降,肝硬化患者小肠细菌过度生长与MHE有相关性。     

Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites

Background/Aims: Translocation of indigenous bacterial from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats.Methods: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria.Results: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice.Conclusions: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.