小肠神经内分泌肿瘤24例临床分析

目的 探讨小肠神经内分泌肿瘤（NETs）的临床特点、治疗方法及预后.方法 对24例小肠神经内分泌肿瘤患者的临床资料进行回顾性分析.结果 分期情况：T1期7例、T2期4例、T3期4例、T4期6例,另3例无法确定.分级情况：G1级10例,G2级7例,NEC 5例,MANEC 2例.免疫组织化学：Syn、CgA、NSE阳性表达率分别为95%、79%、75%.临床表现：上腹疼痛17例,溃疡出血2例,胆系扩张、梗阻性黄疸、瘙痒5例,恶心呕吐、贫血等3例,类癌综合征1例,无症状1例.治疗：18例十二指肠NETs患者中内镜下切除6例,全身姑息化疗1例,胰十二指肠切除11例,其中术后辅助化疗6例;6例空回肠NETs患者中手术切除3例,肝转移灶介入后再行小肠病灶手术切除1例,对症治疗2例.随访：6例十二指肠NETs内镜下切除者均无病生存,11例十二指肠NETs患者术后1例死于心脏疾病,1例死于肺部感染,2例MANEC患者和未行手术治疗的1例NEC患者存活期较短,分别为13个月、10个月、5个月;6例空回肠NETs患者有2例仍然存活,其余4例出现腹腔、肝内广泛播散,均在2年后死亡.结论 小肠神经内分泌肿瘤缺乏特征性临床症状,内镜有助于该病的早期诊断.尽早手术切除肿瘤可提高患者生存率,病理分期和分级与患者的生存预后密切相关.     

基于16S rDNA测序研究白酒对大鼠肠道菌群的影响

为探究浓香型白酒对SD大鼠肠道微生态的影响,通过连续8周灌胃适当剂量乙醇,建立SD大鼠慢性酒精性肝损伤模型,同时,灌胃相同剂量的白酒,考察白酒和乙醇对SD大鼠血脂、肝脏指标的影响及造成的肠道菌群变化。结果显示,连续8周灌胃乙醇造成SD大鼠一定程度的酒精性肝损伤,而白酒组的肝损伤程度显著低于乙醇组。多样性分析表明乙醇组SD大鼠肠道菌群丰富度和多样性降低,而白酒的摄入可以回调这种现象。菌群结构分析表明乙醇干预和白酒干预之间存在显著差异,其中白酒干预组物种组成与对照组更加接近。差异性分析筛选出白酒组和乙醇组的3个潜在差异微生物标志物,分别为g＿Eubacterium＿rumminantium＿group、g＿U29-B03和g＿unclassified＿f＿Oscillospiraceae。该研究结果表明白酒可能通过调节肠道微生态来减轻乙醇诱导的轻度肝损伤。     

富硒菌C5对小鼠肠道菌群结构的影响

研究了富硒菌C5和双歧杆菌三联活菌胶囊、地衣芽孢杆菌活菌胶囊的益生菌制剂对小鼠肠道菌群的影响。将小鼠分为益生菌制剂组A组（三联活菌组）和B组（地衣芽孢杆菌+三联活菌组）、实验组C组（富硒菌C5组）和空白组D组,饲养4周后取小鼠粪便,PCR扩增细菌16S rRNA基因的V3-V4区,用Ⅰllummina HiSeq 2500进行高通量测序,利用QIIME2软件生成不同分类水平上的物种丰度表,对样品Alpha多样性指数进行评估和Beta多样性分析。富硒菌C5和地衣芽孢杆菌活菌胶囊、双歧杆菌三联活菌胶囊一样能调节小鼠肠道菌群丰度和多样性,Alpha多样性的ACE、Chao1和Shannon均有所升高（P<0.05）;富硒菌C5能提高小鼠肠道菌群中Firmicutes（厚壁菌门）和Lactobacillus（乳杆菌属）的相对丰度;降低Staphylococcus（葡萄球菌属）;提高Lachnospiraceae（毛螺菌科）中的Agathobacter（无杆菌属）的相对丰度（P<0.05）。富硒菌C5能够改善机体的肠道微生态,在微生物制剂改善肠道菌群健康方面具有一定的应用价值。     

基于高通量测序分析毛菊苣醇提物对db/db小鼠肠道菌群的影响

该文探究毛菊苣醇提物对糖尿病小鼠（db/db小鼠）肠道菌群的影响。该研究以m/m小鼠为正常对照组（CON组）,db/db小鼠随机分为模型组（MOD组）、二甲双胍组（MET组）、毛菊苣醇提物低剂量组（CGL组）、毛菊苣醇提物高剂量组（CGH组）。灌胃给药8周,对小鼠体质量、空腹血糖、肝脏总胆固醇（TC）、甘油三酯（TG）进行分析,对小鼠粪便进行16S rRNA测序分析,探究毛菊苣醇提物对小鼠肠道菌群的影响。毛菊苣醇提物高剂量组可调节db/db小鼠体质量及血糖,显著降低db/db小鼠TC、TG水平（P<0.05）;测序结果显示CON组、MOD组、CGH组三组小鼠肠道菌群情况存在差异,毛菊苣醇提物给药可改善db/db 小鼠的肠道菌群失调,上调db/db小鼠肠道菌群中有益菌双歧杆菌属（Bifidobacterium）、Romboutsia、普雷沃氏菌属（Prevotella）菌群相对丰度。研究证明了毛菊苣醇提物给药能调节db/db小鼠肠道菌群,通过提高有益菌相对丰度调节糖脂代谢,可为新疆地产毛菊苣药材资源的开发利用提供全新的研究思路。     

The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy

Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.     

植物多酚和多糖经肠道微生态途径互作调节糖脂代谢的研究进展

基于“多酚-多糖-肠道菌群”相互作用发挥机体健康效应已成为精准膳食干预策略和生物医学理论基础研究的热点和发展方向。植物多酚和多糖均具有调节机体健康的生物活性,单一组分因自身结构、理化性质等因素导致其生物利用度较低,不能较好的发挥功效。多酚多糖相互作用形成的复合结构能提高其功能特性,从而更有效地发挥机体健康效应和预防疾病。本文主要从多酚多糖调节糖脂代谢的作用、多酚多糖经肠道微生物途径改善糖脂代谢、多酚多糖相互作用调节糖脂代谢机制等方面进行综述。大量前期研究均证实植物多酚和多糖具有糖脂代谢调节功效,然而涉及两种成分相互作用共同发挥功效及其机制研究还非常有限,本综述为后续研究二者相互作用及其功能特性变化等方面提供参考。     

The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.     

Toward Xeno-Free Differentiation of Human Induced Pluripotent Stem Cell-Derived Small Intestinal Epithelial Cells

The small intestinal epithelium has an important role in nutrition, but also in drug absorption and metabolism. There are a few two-dimensional (2D) patient-derived induced pluripotent stem cell (iPSC)-based intestinal models enabling easy evaluation of transcellular transport. It is known that animal-derived components induce variation in the experimental outcomes. Therefore, we aimed to refine the differentiation protocol by using animal-free components. More specifically, we compared maturation of 2D-cultured iPCSs toward small intestinal epithelial cells when cultured either with or without serum, and either on Geltrex or on animal-free, recombinant laminin-based substrata. Differentiation status was characterized by qPCR, immunofluorescence imaging, and functionality assays. Our data suggest that differentiation toward definitive endoderm is more efficient without serum. Both collagen- and recombinant laminin-based coating supported differentiation of definitive endoderm, posterior definitive endoderm, and small intestinal epithelial cells from iPS-cells equally well. Small intestinal epithelial cells differentiated on recombinant laminin exhibited slightly more enterocyte specific cellular functionality than cells differentiated on Geltrex. Our data suggest that functional small intestinal epithelial cells can be generated from iPSCs in serum-free method on xeno-free substrata. This method is easily converted to an entirely xeno-free method.