肠道菌群在恶性肿瘤治疗中的研究进展

近年来,关于肠道菌群与恶性肿瘤的治疗关系一直都是研究热点。有利的肠道菌群结构可以促进上皮肿瘤或者黑色素瘤患者抗PD-1免疫治疗疗效,并且这种疗效可以通过粪菌移植来实现。对于接受盆腔放疗的患者,肠道菌群结构发生明显变化,而服用益生菌可改善放疗引起的腹泻等不适反应。相关研究表明,化疗后患者的肠道菌群发生明显变化,提升相关菌群的数量可提高化疗耐受性和疗效。调整肠道菌群有望成为恶性肿瘤新的辅助治疗手段。     

粪菌移植在难治性腹泻中的应用进展

难治性腹泻在发病时严重影响患者的日常生活及工作,且目前尚无统一的治疗方法。难治性腹泻患者存在不同程度的肠道菌群失调,因此重建肠道微生态系统可能成为治疗该疾病的有效途径。粪菌移植(FMT)作为一种可重建正常肠道菌群的治疗方法,有潜力成为治疗难治性腹泻的有效方法。近年来,FMT已被应用于部分与肠道菌群失调有关的难治性腹泻的治疗,如复发性艰难梭菌感染、炎症性肠病、肠易激综合征等,均取得了较好的疗效,但至今仍有部分问题尚未得到妥善解决。本文就FMT治疗难治性腹泻的作用机制、在各类难治性腹泻中的临床应用进展及目前所面临的问题进行综述。     

异基因造血干细胞移植对肠道菌群的影响

正常情况下,肠道微生物群多样性对维持免疫稳态至关重要,但其组成及其多样性受多种因素干扰。肠道微生物群组成和多样性的改变与许多疾病如肠道移植物抗宿主病（graft-versus-host disease,GVHD）紧密相关。肠道GVHD是异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo HSCT)后并发症之一,明显增加移植相关死亡率。随着高通量测序技术的不断进步,肠道GVHD与菌群多样性的关系得到了验证。然而国内关于如何改善患者预后方面的研究甚少,作者对allo HSCT后患者的肠道菌群与GVHD之间的关系作一综述,进一步总结通过平衡肠道菌群的多种治疗方法,为临床上改善手术预后,降低患者死亡率提供治疗策略。     

肠道菌群与放射性肠炎的关系及研究进展

肠道菌群是人体的重要组成部分。目前已经证实肠道菌群在高血压、糖尿病、肿瘤和炎症性肠病等疾病的发生发展中发挥重要作用。放射性肠炎（RE）多见于行放疗的肿瘤患者。近年来,肠道菌群与RE的关系成为研究热点。RE与肠道菌群密切相关,其机制可能与肠道菌群失调引起的炎症细胞的浸润及相关细胞因子的表达密切相关。益生菌补充治疗能够缓解部分RE患者的临床症状。最近一些研究聚焦于粪便菌群移植及小分子新药在RE中的治疗作用。笔者总结了近期基于肠道菌群的RE的发生机制及临床应用研究,期望为靶向肠道菌群的治疗提供理论依据。     

肠道菌群与肠道辐射损伤的关系及其机制研究进展

近些年,越来越多的研究人员开始重视肠道菌群与人体健康的关系,并试图探讨其在辐射损伤中的作用。越来越多的证据表明,正常的肠道菌群通过Toll样受体、免疫途径和炎症反应等维持人体的健康。改善肠道菌群、调节菌群的平衡已作为治疗某些疾病的手段之一。本文综述肠道菌群与肠道辐射损伤的关系和机制,以期为放射性肠炎及其他疾病的治疗提供理论依据和指导。     

肠道菌群——运动干预防治代谢性疾病的新靶点

<正>近年来,肠道菌群作为参与机体稳态调节的新靶点已引起医学界的广泛关注。肠道菌群寄居于人体肠道,通过对肠道的保护、营养以及参与调节机体代谢而对宿主健康产生影响。机体肠道菌群失调可诱发包括肥胖、非酒精性脂肪肝、糖尿病和癌症等多种代谢相关疾病。因此,肠道菌群的改变是评估机体生理健康状况的一项重要指标。运动作为一种环境刺激性因素可有效调节肠道菌群的成分和结构、提高肠道菌群的丰     

肠道菌群失调与结直肠癌的相关研究进展

人体肠道微生物组与许多健康因素有关,但研究之间的差异限制了它们之间效应的探索。本文综述了肠道菌群失调与结直肠癌的发病机制之间的关系,讨论了调节肠道菌群用以防治结直肠癌的可行性,为结直肠癌的预防诊断及治疗打开新思路。     

肠道微生物在放射性肠损伤及其治疗中的研究进展

放射性肠损伤（RIII）是腹盆腔肿瘤放疗中常见的不良反应,严重影响着癌症患者的后续治疗计划和幸存者的生活质量,其患病人数已远超炎症性肠病,亟需有效的防治措施。已有大量研究结果证明,RIII与肠道微生物群失调相关,而粪菌移植（FMT）可以帮助患者恢复肠道微生物群的丰度和多样性,可以作为RIII治疗中的潜在方法。笔者着重综述了肠道微生物在RIII发生和发展过程中的作用及其机制,以及FMT在RIII治疗中的应用。     

运动与肠道菌群相关研究的热点主题和趋势——基于文献计量学分析

目的：梳理运动与肠道菌群的相关研究,明晰其发展脉络及动态,为后续相关研究提供参考。方法：基于CiteSpace可视化软件,对Web of Science Core Collection(WoS核心合集)数据库收录的522篇文献进行分析,梳理出运动与肠道菌群相关研究领域的热点主题、研究趋势。主要结果：研究热点紧密围绕运动、肠道菌群、疾病、营养与饮食、益生菌展开,具体热点主题包括：运动与疾病人群肠道菌群关系的研究;剧烈运动与运动员胃肠道症状关系的研究;运动、饮食、营养及益生菌关系的研究。研究趋势主要有：干预方案和健康获益之间的剂量效应特征的挖掘;运动对肠道菌群作用机制的探索;疾病类型以及疗效指标的转变。     

运动对肠道屏障功能的影响研究进展

组织器官之间的协调互作是机体维持能量代谢稳态的重要前提,而肠道菌群作为机体重要的"内分泌器官",菌群紊乱引起的肠-肝轴、肠-脂肪轴失衡是导致机体肥胖、2型糖尿病、脂肪肝等代谢性疾病的重要病理基础,其机制可能与肠道屏障功能受损相关.运动可促进机体能量代谢,已成为临床预防和治疗多种慢性疾病的重要手段.现已证实,运动也是影响...     

Gliomatosis cerebri evaluated by <Superscript>18</Superscript>Fα-methyl tyrosine positron-emission tomography

Gliomatosis cerebri is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. CT and MRI show diffuse abnormal density or signal, without mass effect, and because these findings are nonspecific, it is difficult to make a definitive diagnosis. Our purpose was to assess the usefulness of a new tumour-detecting amino acid tracer for positron-emission tomography (PET), L-[3-¹⁸F] -methyl tyrosine (FMT), in patients with gliomatosis cerebri. We performed FMT PET, fluorodeoxyglucose FDG PET and MRI eight patients with gliomatosis cerebri and six with non-neoplastic disease, whose MRI also showed diffuse high signal on T2-weighted images. Standardised uptake (SUV) of FMT and FDG in the area of gliomatosis was obtained and the tumour-to-normal cortex (T/N) ratio of this was compared. The tumours were shown on FMT PET as areas of increased uptake, except in one patient with severe intracranial hypertension. There were significant differences between the SUV of FMT and the T/N ratio of FMT in patients and in controls (both P<0.01), and between the T/N ratio of FMT and FDG in patients (P <0.01). Increased uptake of FMT PET strongly suggests neoplasia. FMT PET is valuable for differentiating gliomatosis cerebri from non-neoplastic diseases showing similar diffuse high signal on T2-weighted images and little contrast enhancement.     

18F alpha-methyl tyrosine PET studies in patients with brain tumors.

We have developed 18F-labeled alpha-methyl tyrosine (FMT) for PET imaging. The aim of this study was to evaluate the clinical application potential of FMT for patients with brain tumors. METHODS: Eleven healthy volunteers and 20 patients with brain tumors were injected with 185 MBq (5 mCi) FMT. In 3 healthy volunteers, whole-body imaging and urinary and plasma analysis were conducted for the assessment of the biodistribution of FMT. The normal range of cortical standardized uptake value (SUV) as a reference for comparing tumor SUV of FMT was estimated by using PET data obtained at 30 min postinjection in 8 healthy volunteers. Dynamic PET scans were conducted for 100 min in 4 healthy volunteers and for 30 min in 15 patients with brain tumors. The 10-min static images in another 4 volunteers and all patients were obtained at 30 min postinjection. In 13 patients, FMT uptake in the brain tumor was compared with 18F-fluorodeoxyglucose (FDG). Tumor-to-normal cortex count (T/N) ratio and tumor-to-white matter count (T/W) ratio and SUVs of brain tumors were determined on FMT and FDG PET images. RESULTS: Approximately 1480 MBq (40 mCi) FMT were produced in one radiosynthesis. Percentage injected dose (%ID) of FMT in the brain ranged from 2.8% to 4.9%, and approximately 50%ID of FMT was excreted in urine during 60 min postinjection, of which 86.6% was unmetabolized FMT. A faint physiological brain uptake with SUV of 1.61 +/- 0.32 (mean +/- SD, n = 8) was observed in healthy volunteers. Tumor SUV of FMT ranged from 1.2 to 8.2, with mean value of 2.83 +/- 1.57 (n = 23), which was significantly higher than that of the cortical area in healthy volunteers (P < 0.01). T/N and T/W ratios of FMT were significantly higher than those of FDG (2.53 +/- 1.31 versus 1.32 +/- 1.46, P < 0.001; 3.99 +/- 2.10 versus 1.39 +/- 0.65, P < 0.0001, respectively). CONCLUSION: FMT, like other radiolabeled amino acids, can provide high-contrast PET images of brain tumors.     

Evaluation of O-[18F]fluoromethyl-d-tyrosine as a radiotracer for tumor imaging with positron emission tomography

O-[¹⁸F]Fluoromethyl-d-tyrosine (d-[¹⁸F]FMT) has been reported as a potential tumor-detecting agent for positron emission tomography (PET). However, the reason why d-[¹⁸F]FMT is better than l-[¹⁸F]FMT is unclear. To clarify this point, we examined the mechanism of their transport and their suitability for tumor detection. The stereo-selective uptake and release of enantiomerically pure d- and l-[¹⁸F]FMT by rat C6 glioma cells and human cervix adenocarcinoma HeLa cells were examined. The results of a competitive inhibition study using various amino acids and a selective inhibitor for transport system L suggested that d-[¹⁸F]FMT, as well as l-[¹⁸F]FMT, was transported via system L, the large neutral amino acid transporter, possibly via LAT1. The in vivo distribution of both [¹⁸F]FMT and [¹⁸F]FDG in tumor-bearing mice and rats was imaged with a high-resolution small-animal PET system. In vivo PET imaging of d-[¹⁸F]FMT in mouse xenograft and rat allograft tumor models showed high contrast with a low background, especially in the abdominal and brain region. The results of our in vitro and in vivo studies indicate that l-[¹⁸F]FMT and d-[¹⁸F]FMT are specifically taken up by tumor cells via system L. d-[¹⁸F]FMT, however, provides a better tumor-to-background contrast with a tumor/background (contralateral region) ratio of 2.741 vs. 1.878 with the l-isomer, whose difference appears to be caused by a difference in the influence of extracellular amino acids on the uptake and excretion of these two isomers in various organs. Therefore, d-[¹⁸F]FMT would be a more powerful tool as a tumor-detecting agent for PET, especially for the imaging of a brain cancer and an abdominal cancer.     

拉米夫定预防肝移植术后乙型肝炎病毒再感染的研究

为探讨拉米夫定对预防原位肝移植术后乙型肝炎病毒再感染的作用。对7例乙型肝炎病毒感染相关终末期肝病患者行同种肝移植,5例于肝移植前后予拉米夫定预防乙型肝炎病毒再感染,2例予普通抗病毒药物阿昔洛韦治疗。结果显示：应用拉米夫定组术后均无乙型肝炎病毒再感染,其中3例随访超过6个月,亦未发现有YMDD变异发生;2例未予拉米夫定治疗术后均发生乙型肝炎病毒再感染,提示拉米夫定能有效地预防肝移植术后乙型肝炎病毒再感染。     

PET imaging of musculoskeletal tumours with fluorine-18 alpha-methyltyrosine: comparison with fluorine-18 fluorodeoxyglucose PET

Fluorine-18 labelled alpha-methyltyrosine (FMT) was developed for positron emission tomography (PET) imaging, and its potential for clinical application in patients with brain tumours has been demonstrated. This is the first trial to compare FMT with 18F-fluoro-2-deoxy-D-glucose (FDG) for the evaluation of musculoskeletal tumours. Seventy-five patients were examined with both FMT- and FDG-PET within a 2-week period. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) for both FMT and FDG in lesions were also generated and compared with histological findings. A significant correlation between FMT and FDG SUVs was found for all lesions (r=0.769, P<0.0001), and mean values for malignant tumours were significantly higher than those for benign lesions in both FMT- and FDG-PET. The diagnostic sensitivities and specificities for malignancy were 72.7% and 84.9%, respectively, using FMT with a cut-off SUV of 1.2, and 72.7% and 66.0%, respectively, using FDG with a cut-off SUV of 1.9. The resultant accuracy with FMT was 81.3%, higher than that for FDG (68.0%), and the difference with respect to specificity was significant (chi2cal=5.0625, P<0.05). On the other hand, while a significant correlation was found between malignant tumour grade and SUV with both FMT- (rho=0.656) and FDG-PET (rho=0.815), only the latter demonstrated significant differences among grades I, II and III. FMT and FDG for PET appear equally effective at detecting musculoskeletal tumours. In evaluating musculoskeletal tumours, FMT may be superior to FDG in the differentiation between benign and malignant tumours, while FDG may be the better choice for non-invasive malignancy grading.     

肝肾联合移植及相关问题处理

目的探讨肝肾联合移植及其相关问题。方法对1例巨大的多囊肝、多囊肾患者和1例肝炎后肝硬化、肝癌合并肾功能衰竭患者实施一期肝肾联合移植。供体器官采用UW液原位灌注,快速切取。肝移植分别采用经典式或背驮式原位肝移植,肾移植采用常规方法。术后免疫抑制剂采用三联免疫方案。结果两例患者术后移植器官立即发挥功能。例1术后第2天发生急性肺损伤,第11天发生ARDS,经积极治疗后控制;例2肝、肾功能正常,未出现急性排斥反应和原发病复发等问题。结论肝肾联合移植是治疗肝肾终末期疾病的方法之一,完善的手术、严密的围手术期监测是肝肾联合移植成功的重要条件,肝肾联合移植手术可以取得良好的临床治疗效果,但在技术上较单纯的肝移植或肾移植要求更高、更复杂。