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Neutrophils in Intestinal Inflammation: What We Know and What We Could Expect for the Near Future 肠道炎症中的中性粒细胞:我们所知道的以及在不久的将来我们可以期待的
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-10-04 DOI: 10.3390/gidisord4040025
L. Arosa, M. Camba-Gómez, J. Conde-Aranda
Neutrophils are short-lived cells that play a crucial role in inflammation. As in other tissues, these polymorphonuclear phagocytes are involved in the intestinal inflammatory response, on the one hand, contributing to the activation and recruitment of other immune cells, but on the other hand, facilitating intestinal mucosa repair by releasing mediators that aid in the resolution of inflammation. Even though these responses are helpful in physiological conditions, excessive recruitment of activated neutrophils in the gut correlates with increased mucosal damage and severe symptoms in patients with inflammatory bowel disease (IBD) and pre-clinical models of colitis. Thus, there is growing interest in controlling their biology to generate novel therapeutic approaches capable of reducing exacerbated intestinal inflammation. However, the beneficial and harmful effects of neutrophils on intestinal inflammation are still controversial. With this review, we summarise and discuss the most updated literature showing how neutrophils (and neutrophil extracellular traps) contribute to developing and resolving intestinal inflammation and their putative use as therapeutic targets.
中性粒细胞是在炎症中起关键作用的短命细胞。与其他组织一样,这些多形核吞噬细胞参与肠道炎症反应,一方面有助于其他免疫细胞的激活和募集,但另一方面,通过释放有助于解决炎症的介质来促进肠粘膜修复。尽管这些反应在生理条件下是有帮助的,但在炎症性肠病(IBD)和结肠炎临床前模型患者中,肠道中活化的中性粒细胞的过度募集与粘膜损伤增加和严重症状相关。因此,人们越来越感兴趣的是控制它们的生物学,以产生能够减少加重的肠道炎症的新的治疗方法。然而,中性粒细胞对肠道炎症的有益和有害影响仍然存在争议。在这篇综述中,我们总结并讨论了最新的文献,这些文献表明中性粒细胞(和中性粒细胞外陷阱)如何有助于发展和解决肠道炎症,以及它们作为治疗靶点的假定用途。
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引用次数: 4
Intestinal Ultrasound in the Assessment of Luminal Crohn’s Disease 肠道超声在评估Luminal Crohn病中的应用
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-09-28 DOI: 10.3390/gidisord4040024
A. Bohra, D. V. van Langenberg, A. Vasudevan
Crohn’s disease is a chronic inflammatory disease affecting the gastrointestinal tract. Expert guidelines now recommend regular objective assessments as part of a treat-to-target approach. Intestinal ultrasound provides a noninvasive, patient-friendly modality for assessing Crohn’s disease without the risk of radiation exposure and does not require fasting or bowel preparation. Enhancement techniques, including oral and intravenous contrast, can improve disease-activity and complication detection. Due to its acceptability, intestinal ultrasound can be performed frequently, allowing for closer disease-activity monitoring and treatment adjustments. There have been significant advances in the utility of intestinal ultrasound; particularly for assessing disease activity during pregnancy and fibrosis detection utilising elastography. This review provides a comprehensive overview of performing intestinal ultrasound, the diagnostic accuracy, role in disease-activity monitoring, and recent advances in utilising ultrasound for the assessment of luminal Crohn’s disease.
克罗恩病是一种影响胃肠道的慢性炎症性疾病。专家指南现在建议将定期客观评估作为从治疗到目标方法的一部分。肠道超声为评估克罗恩病提供了一种无创的、对患者友好的方式,没有辐射暴露的风险,也不需要禁食或肠道准备。增强技术,包括口服和静脉造影,可以改善疾病活动性和并发症的检测。由于它的可接受性,肠道超声可以经常进行,允许更密切的疾病活动监测和治疗调整。肠道超声的应用已经取得了重大进展;特别是用于评估怀孕期间的疾病活动和利用弹性成像检测纤维化。本文综述了肠道超声、诊断准确性、疾病活动监测中的作用以及利用超声评估肠道克罗恩病的最新进展。
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引用次数: 2
Impact of the Gut-Brain Hormonal Axis and Enteric Peptides in the Development of Food Neophobia in Children with Genetically Determined Hypersensitivity to the Bitter Taste 肠-脑激素轴和肠肽在遗传决定的对苦味过敏的儿童食物恐惧症发展中的影响
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-09-28 DOI: 10.3390/gidisord4040023
A. Wiernicka, K. Piwczyńska, Paulina Mika-Stępkowska, Dorota Kazimierska, P. Socha, A. Rybak
Objective: The aim of this prospective study was to determine the role of the gut-brain hormonal axis and the effect of the enteric peptides, as well as the role of genetically determined sensitivity to the bitter taste, on the development of child food neophobia (CFN). Methods: 114 children were enrolled in the study: 43 in food neophobia group (FNG), 21 In the control group (CG) and 50 in prospective group (PG). All patients were assessed with the child food neophobia scale (CFNS), underwent an oral 6-propylthiouracil (6-PROP) test, buccal swab for bitter-taste genotyping, anthropometric measurements, and were tested for serum levels of leptin, adiponectin, insulin-like growth factor-1(IGF-1), ghrelin, and neuropeptide Y (NPY), and complete blood count (CBC); measurements were taken from a blood sample after 4 h fasting. Results: Subjects from FNG were more often hypersensitive to bitter taste (6-PROP) than CG (p = 0.001). There was no correlation between the result of genetic analysis and CFNS (p = 0.197), nor the body mass index (BMI) at the age of 18–36 months (p = 0.946) found. Correlation between 6-PRO perception and genotype have not been confirmed (p = 0.064). The score of CFNS was positively related to the serum level of NPY (p = 0.03). BMI percentile was negatively related to serum level of NPY (p = 0.03), but positively related to leptin serum level (p = 0.027). Conclusions: Bitter taste sensitivity to 6-PROP plays an important role in the development of the CFN, but correlation between 6-PROP perception and genotype have not been confirmed. Children with food neophobia due to elevated serum NPY level should be constantly monitored in order to control the nutritional status at a later age.
目的:本前瞻性研究的目的是确定肠脑激素轴和肠肽的作用,以及遗传决定的对苦味的敏感性在儿童食物新恐惧症(CFN)发展中的作用。方法:114名儿童被纳入研究:43名为食物新恐惧症组(FNG),21名为对照组(CG),50名为前瞻性组(PG)。所有患者均采用儿童食物新恐惧症量表(CFNS)进行评估,接受口服6-丙基硫氧嘧啶(6-PROP)测试、口腔拭子苦味基因分型、人体测量,并检测血清瘦素、脂联素、胰岛素样生长因子-1(IGF-1)、胃饥饿素和神经肽Y(NPY)水平以及全血细胞计数(CBC);从禁食4小时后的血液样本中进行测量。结果:FNG受试者对苦味(6-PROP)比CG更敏感(p=0.001)。遗传分析结果与CFNS(p=0.017)和18-36个月大时的体重指数(BMI)之间没有相关性(p=0.0946)。6-PROP感知与基因型之间的相关性尚未得到证实(p=0.064)。CFNS评分与血清NPY水平呈正相关(p=0.03)。BMI百分位数与血清NPY水平呈负相关(p=0.003),但与血清瘦素水平呈正相关性(p=0.027)。结论:对6-PROP的苦味敏感性在CFN的发展中起着重要作用,但6-PROP感知和基因型之间的相关性尚未得到证实。应不断监测因血清NPY水平升高而患有食物新恐惧症的儿童,以控制其日后的营养状况。
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引用次数: 0
Infliximab and Plant-Based Diet as First-Line Therapy Followed by Corticosteroid Therapy for Severe Ulcerative Colitis: A Case Report 英夫利昔单抗和植物性饮食作为治疗重度溃疡性结肠炎的一线治疗,后加皮质类固醇治疗:1例报告
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-09-26 DOI: 10.3390/gidisord4040022
M. Chiba, Tsuyotoshi Tsuji, R. Masai, M. Odashima, M. Sageshima
We developed infliximab and a plant-based diet as first-line (IPF) therapies for severe ulcerative colitis (UC). It increased the remission rate and decreased the colectomy rate compared to those of current standards. We encountered a case with severe UC in which the consecutive use of IPF therapy and corticosteroid therapy was required to induce remission. A 21-year-old male worker developed diarrhea, abdominal pain, marked weight loss from 70 to 55 kg, and anorexia. He was diagnosed with severe ulcerative colitis. IPF therapy was initiated. Improvement in symptoms and biomarkers was seen soon after the first infusion of infliximab (300 mg). Further improvement in symptoms was observed after both the second and third infliximab infusions. Loose stool and abdominal pain on defecation were still present, however, and biomarkers were above the reference range. Therefore, oral prednisolone (40 mg/day) was consecutively initiated. This resulted in clinical and endoscopic remission. In conclusion, we present a severe UC case in which the response to IPF therapy was insufficient. Consecutive oral prednisolone successfully induced remission. This new stepwise modality will make IPF therapy the first-choice therapy for severe UC.
我们开发了英夫利昔单抗和植物性饮食作为严重溃疡性结肠炎(UC)的一线(IPF)疗法。与现行标准相比,它增加了缓解率,降低了结肠切除术率。我们遇到了一个严重UC的病例,其中连续使用IPF治疗和皮质类固醇治疗需要诱导缓解。一名21岁男性工人出现腹泻、腹痛,体重从70公斤明显下降至55公斤,并出现厌食症。他被诊断患有严重的溃疡性结肠炎。开始IPF治疗。首次输注英夫利昔单抗(300 mg)后,症状和生物标志物得到改善。在第二次和第三次英夫利昔单抗输注后,观察到症状进一步改善。然而,排便时稀便和腹痛仍然存在,生物标志物高于参考范围。因此,连续开始口服强的松龙(40mg /天)。这导致临床和内镜缓解。总之,我们提出了一个严重的UC病例,其中对IPF治疗的反应不足。连续口服强的松龙成功诱导缓解。这种新的渐进式方式将使IPF治疗成为严重UC的首选治疗方法。
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引用次数: 1
Onset of Ulcerative Colitis in a Patient with Type 2 Diabetes: Efficacy of a Plant-Based Diet for Both Diseases 2型糖尿病患者溃疡性结肠炎的发病:植物性饮食对两种疾病的疗效
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-09-23 DOI: 10.3390/gidisord4040021
M. Chiba, M. Komatsu, Mihoko Hosoba, K. Hatano, Masato Takeda
No case has been reported in which ulcerative colitis occurred in a patient with type 2 diabetes mellitus and the patient was treated with a plant-based diet. A 56-year-old man with a 3-year history of diabetes noticed bloody stool about 2 months after his worst glycated hemoglobin A1c test. Endoscopy revealed diffuse inflammation in the rectum. He was diagnosed with ulcerative colitis (proctitis, mild severity). He underwent educational hospitalization. A plant-based diet (1400 kcal/day) was provided. The same dosage of metformin was continued, but no medication was prescribed for ulcerative colitis. At the end of hospitalization, fecal occult blood 271 ng/mL became negative. Glycated hemoglobin A1c 6.9% had decreased to 6.6%. Two months after discharge, glycated hemoglobin A1c decreased to normal for the first time in 3.5 years. Ulcerative colitis had been in remission without medication for one and a half years after the educational hospitalization. Thereafter, however, he experienced two flareups. Deterioration in glycated hemoglobin A1c preceded the flareups. We described a scarcely reported case in which ulcerative colitis occurred in a patient with diabetes and the patient was treated with a plant-based diet. The plant-based diet was effective for both diseases. It seemed that the status of diabetes influenced the onset and relapse of ulcerative colitis.
目前尚无2型糖尿病患者发生溃疡性结肠炎的病例报告,该患者采用植物性饮食治疗。56岁男性,糖尿病病史3年,最差糖化血红蛋白A1c检查2个月后发现便血。内镜检查显示直肠弥漫性炎症。诊断为溃疡性结肠炎(直肠炎,轻度)。他接受了教育住院治疗。提供植物性饮食(1400千卡/天)。继续使用相同剂量的二甲双胍,但没有为溃疡性结肠炎开处方。住院结束时,粪便隐血271 ng/mL变为阴性。糖化血红蛋白A1c由6.9%降至6.6%。出院后2个月,糖化血红蛋白A1c为3.5年来首次降至正常。溃疡性结肠炎在教育住院治疗后一年半的时间内没有药物治疗,病情得到缓解。然而,此后,他经历了两次发作。糖化血红蛋白A1c恶化先于发作。我们描述了一个几乎没有报道的病例,其中溃疡性结肠炎发生在糖尿病患者,患者接受植物性饮食治疗。植物性饮食对这两种疾病都有效。糖尿病状况影响溃疡性结肠炎的发病和复发。
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引用次数: 1
Retrospective Analysis of the Safety of FOLFOX Compared to CAPOX for Adjuvant Treatment of Stage III Colorectal Cancer in Newfoundland Patients FOLFOX与CAPOX辅助治疗纽芬兰癌症III期结直肠癌的安全性回顾性分析
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-09-08 DOI: 10.3390/gidisord4030020
Josh N. McShane, D. Armstrong
Background: Capecitabine and oxaliplatin (CAPOX) and infusional 5-fluouracil, folinic acid, and oxaliplatin (FOLFOX) are the two chemotherapy regimens in current clinical use for the adjuvant treatment of colorectal cancer (CRC). Many centers in Newfoundland lack the resources to support the home infusion program required for FOLFOX, leaving CAPOX as the sole treatment option. This study aimed to review if Newfoundland patients receiving CAPOX experience greater treatment-induced toxicities. Methods: A multicenter retrospective cohort study of 93 Stage III CRC patients. The frequency and severity of toxicities, healthcare resource utilization, and treatment completion rates were compared between the two treatment options. Results: Grade 3 diarrhea and grade 1 or 2 nausea/vomiting were more common in CAPOX compared to FOLFOX-treated patients (26.9% versus 2.99%, p = 0.002; 61.5% versus 31.8%; p = 0.048, respectively). Grade 1 or 2 mucositis was more common with FOLFOX (35.8% versus 3.9%, p = 0.002). CAPOX was associated with higher rates of severe toxicity (53.9% versus 25.4%, p = 0.009), while rates of grade 1 and 2 toxicities were not significantly different between groups. CAPOX-treated patients were greater than twice as likely to require emergency department treatment secondary to toxicity (mean 0.692 visits per patient versus 0.313 in FOLFOX patients, p < 0.001) and the proportion of patients that were hospitalized secondary to CAPOX toxicity was greater. Significantly more FOLFOX patients were able to finish their prescribed treatment plans compared to CAPOX patients (89.5% versus 53.8%; p < 0.001). Conclusions: Compared to FOLFOX-treated patients, CAPOX patients are more likely to experience toxicities of greater severity, require emergency services secondary to treatment-related toxicity, and to discontinue therapy. This reflects a reduced standard of care that may decrease patient safety and quality of life.
背景:卡培他滨和奥沙利铂(CAPOX)以及输注5-氟尿嘧啶、亚叶酸和奥沙利拉丁(FOLFOX)是目前临床上辅助治疗癌症(CRC)的两种化疗方案。纽芬兰的许多中心缺乏资源来支持FOLFOX所需的家庭输液计划,使CAPOX成为唯一的治疗选择。本研究旨在审查接受CAPOX治疗的纽芬兰患者是否经历了更大的治疗诱导毒性。方法:对93例III期CRC患者进行多中心回顾性队列研究。比较两种治疗方案的毒性发生频率和严重程度、医疗资源利用率和治疗完成率。结果:与FOLFOX治疗的患者相比,CAPOX的3级腹泻和1或2级恶心/呕吐更常见(分别为26.9%和2.99%,p=0.002;61.5%和31.8%;p=0.048)。FOLFOX的1级或2级粘膜炎更常见(35.8%对3.9%,p=0.002)。CAPOX的严重毒性发生率较高(53.9%对25.4%,p=0.009),而1级和2级毒性发生率在各组之间没有显著差异。接受CAPOX治疗的患者因毒性而需要急诊科治疗的可能性是其他患者的两倍多(平均每位患者就诊0.692次,而FOLFOX患者就诊0.313次,p<0.001),因CAPOX毒性而住院的患者比例更高。与CAPOX患者相比,能够完成处方治疗计划的FOLFOX患者明显更多(89.5%对53.8%;p<0.001)。结论:与接受FOLFOX治疗的患者相比,CAPOX患者更有可能经历更严重的毒性,需要治疗相关毒性后的紧急服务,并停止治疗。这反映了护理标准的降低,可能会降低患者的安全和生活质量。
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引用次数: 0
Evaluation of Accuracy and Feasibility of a New-Generation Ultra-Rapid Urease Test for Detection of Helicobacter pylori Infection 新一代超快速脲酶检测幽门螺杆菌感染的准确性和可行性评价
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-08-26 DOI: 10.3390/gidisord4030019
Marco Cagnoni, C. Pagnini, M. Crovaro, A. Aucello, R. Urgesi, L. Pallotta, G. Fanello, M. D. Di Paolo, M. Graziani
Helicobacter pylori (Hp) infection can be diagnosed by invasive and noninvasive methods, and, among the former, Rapid Urease Tests (RUTs) are an important option. Accuracy and rapidity of results are fundamental for RUTs. The aim of the study is to prospectively evaluate the sensitivity, specificity and time to positivity of a new-generation ultra-rapid urease test (iNatal duo test) for Hp detection and compare the results with other available RUTs [CLO Test (Campylobacter-Like Organism Test), CP Test (Campylobacter pylori Test) and Pronto Dry]. Gastric biopsies were taken in consecutive patients undergoing upper endoscopy: two in the antrum and two in the body for histology, and one in the antrum and one in the body for each RUT. RUTs were read at 1, 5, 15, 30 and 60 min, 3 h and 24 h after biopsy insertion into the reagent. Histology was considered as “gold standard”. The performance of the tests was evaluated in patients not taking proton pump inhibitors (PPI) (n = 924) by calculation of sensitivity, specificity and positive and negative predictive value. Agreement rate (κ) for every RUT and histology was calculated and compared. The performance of the iNatal duo test was also tested in a subgroup of patients taking PPI (n = 198). Hp was positive in 225/924 patients (24.3%) not taking PPIs and in 56/198 (28.3%) who were taking PPIs. The iNatal duo test was more sensitive than the other RUTs for detecting Hp at every time point. The sensitivity at 5 min was 96.2% in patients not taking PPIs and 92.2% in patients taking PPIs. κ with histology was higher for the iNatal duo test than any other RUT (at 30 min: iNatal duo 0.99, CLO 0.60, CP 0.78, Pronto 0.85, at 15 min: iNatal duo 0.99, CLO 0.46, CP 0.63, Pronto 0.71). In a prospective study, the iNatal duo test demonstrated high accuracy and rapidity for Hp detection, both in patients with and without PPI therapy. This new generation of ultra-rapid urease test could be useful for the rapid and correct management of patients undergoing upper GI endoscopy for suspected Hp infection.
幽门螺杆菌(Hp)感染可通过侵入性和非侵入性方法诊断,其中快速脲酶试验(RUTs)是一种重要的选择。结果的准确性和快速性是RUTs的基础。本研究的目的是前瞻性评估新一代超快速脲酶试验(iNatal duo试验)检测Hp的敏感性、特异性和阳性时间,并将结果与其他可用的RUTs [CLO试验(弯曲杆菌样生物试验)、CP试验(幽门螺旋弯曲杆菌试验)和Pronto Dry试验]进行比较。连续接受上胃镜检查的患者进行胃活检:胃窦2个,体内2个用于组织学检查,胃窦各1个,体内1个。在活检组织插入试剂后1、5、15、30和60分钟、3小时和24小时读取RUTs。组织学被认为是“金标准”。在未服用质子泵抑制剂(PPI)的患者(n = 924)中,通过计算敏感性、特异性和阳性和阴性预测值来评估这些试验的性能。计算各RUT和组织学的一致性率(κ)并进行比较。在服用PPI的患者亚组(n = 198)中也测试了atal duo测试的表现。未服用PPIs的924例患者中有225例(24.3%)Hp阳性,服用PPIs的198例患者中有56例(28.3%)Hp阳性。在每个时间点,新生儿二联试验对Hp的检测均较其他rut灵敏。未服用PPIs的患者5分钟的敏感性为96.2%,服用PPIs的患者为92.2%。在iNatal duo试验中,κ与组织学的关系高于其他RUT (30 min时:iNatal duo 0.99, CLO 0.60, CP 0.78, Pronto 0.85, 15 min时:iNatal duo 0.99, CLO 0.46, CP 0.63, Pronto 0.71)。在一项前瞻性研究中,在接受和未接受PPI治疗的患者中,iNatal duo试验都显示出Hp检测的准确性和快速性。这种新一代的超快速脲酶试验可用于快速、正确地处理疑似Hp感染的上消化道内镜患者。
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引用次数: 1
Identification of a Five-MiRNA Expression Assay to Aid Colorectal Cancer Diagnosis 五-三核糖核酸表达检测法辅助大肠癌癌症诊断的鉴定
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-08-19 DOI: 10.3390/gidisord4030018
M. Davey, G. Feeney, H. Annuk, Maxwell Paganga, E. Holian, A. Lowery, M. Kerin, N. Miller
Introduction: One-third of colorectal cancer (CRC) patients present with advanced disease, and establishing control remains a challenge. Identifying novel biomarkers to facilitate earlier diagnosis is imperative in enhancing oncological outcomes. We aimed to create miRNA oncogenic signature to aid CRC diagnosis. Methods: Tumour and tumour-associated normal (TAN) were extracted from 74 patients during surgery for CRC. RNA was isolated and target miRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Regression analyses were performed in order to identify miRNA targets capable of differentiating CRC from TAN and compared with two endogenous controls (miR-16 and miR-345) in each sample. Areas under the curve (AUCs) in Receiver Operating Characteristic (ROC) analyses were determined. Results: MiR-21 (β-coefficient:3.661, SE:1.720, p = 0.033), miR-31 (β-coefficient:2.783, SE:0.918, p = 0.002), and miR-150 (β-coefficient:−4.404, SE:0.526, p = 0.004) expression profiles differentiated CRC from TAN. In multivariable analyses, increased miR-31 (β-coefficient:2.431, SE:0.715, p < 0.001) and reduced miR-150 (β-coefficient:−4.620, SE:1.319, p < 0.001) independently differentiated CRC from TAN. The highest AUC generated for miR-21, miR-31, and miR-150 in an oncogenic expression assay was 83.0% (95%CI: 61.7–100.0, p < 0.001). In the circulation of 34 independent CRC patients and 5 controls, the mean expression of miR-21 (p = 0.001), miR-31 (p = 0.001), and miR-150 (p < 0.001) differentiated CRC from controls; however, the median expression of miR-21 (p = 0.476), miR-31 (p = 0.933), and miR-150 (p = 0.148) failed to differentiate these groups. Conclusion: This study identified a five-miRNA signature capable of distinguishing CRC from normal tissues with a high diagnostic test accuracy. Further experimentation with this signature is required to elucidate its diagnostic relevance in the circulation of CRC patients.
简介:1/3的癌症(CRC)患者患有晚期疾病,建立控制仍然是一个挑战。识别新的生物标志物以促进早期诊断对于提高肿瘤学结果至关重要。我们的目的是创建miRNA致癌特征,以帮助CRC诊断。方法:从74例CRC患者中提取肿瘤和肿瘤相关正常(TAN)。分离RNA,并使用实时逆转录聚合酶链反应对靶miRNA进行定量。进行回归分析以鉴定能够区分CRC和TAN的miRNA靶标,并与每个样品中的两种内源性对照(miR-16和miR-345)进行比较。测定受试者操作特征(ROC)分析中的曲线下面积(AUCs)。结果:MiR-21(β-系数:3.661,SE:1.720,p=0.033)、MiR-31(β-系数值:2.783,SE:0.918,p=0.002)和MiR-150(β系数:−4.404,SE:0.526,p=0.004)的表达谱将CRC与TAN区分开来。在多变量分析中,miR-31增加(β-系数:2.431,SE:0.715,p<0.001)和miR-150减少(β系数:−4.620,SE:1.319,p<001)独立区分CRC和TAN。在致癌表达测定中,miR-21、miR-31和miR-150产生的最高AUC为83.0%(95%CI:61.7–100.0,p<0.001)。在34名独立CRC患者和5名对照组的循环中,miR21(p=0.001)、miR-31(p=001)和miR-150(p<001)的平均表达将CRC与对照组区分开来;然而,miR-21(p=0.476)、miR-31(p=0.933)和miR-150(p=0.148)的中值表达未能区分这些组。结论:本研究鉴定了一种能够以高诊断准确性区分CRC和正常组织的五种miRNA特征。需要对该特征进行进一步的实验,以阐明其在CRC患者循环中的诊断相关性。
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引用次数: 1
Fecal Calprotectin, Chitinase 3-Like-1, S100A12 and Osteoprotegerin as Markers of Disease Activity in Children with Crohn’s Disease 粪钙卫蛋白、几丁质酶3-Like-1、S100A12和骨保护蛋白作为克罗恩病儿童疾病活动的标志物
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-08-04 DOI: 10.3390/gidisord4030017
A. Volkers, Laura Appleton, R. Gearry, C. Frampton, F. D. de Voogd, A. M. Peters van Ton, S. Leach, D. Lemberg, A. Day
Fecal calprotectin (FC), chitinase 3-like-1 protein (CHI3L1), S100A12 and osteoprotegerin (OPG) are biomarkers of intestinal inflammation. This cross-sectional study aimed to evaluate these biomarkers in a cohort of children with Crohn’s disease (CD) and compare them with other measures of disease activity. Stool samples from children with CD were used to measure FC, CHI3L1, S100A12 and OPG by enzyme-linked immunosorbent assay. Serum inflammatory markers were measured and pediatric CD disease activity index (PCDAI) scores calculated. The simple endoscopic score for CD (SES-CD) was reported for a subgroup who underwent ileocolonoscopy corresponding with the stool samples. Sixty-five children were recruited. Children in clinical remission had lower FC and CHI3L1 levels than those with active disease (FC: 277 vs. 1648 µg/g, p = 0.012; CHI3L1: 23 vs. 227 ng/g, p = 0.013). FC levels differed between patients with clinically active or inactive isolated ileal CD. Although FC and CHI3L1 levels correlated strongly (r = 0.83), none of the fecal markers correlated well with serum markers. Only FC and OPG correlated with SES-CD scores (r = 0.57 and r = 0.48, respectively). In conclusion, FC correlated with both endoscopic and clinical disease activity and was the only biomarker that differentiated between active and inactive ileal CD. CHI3L1 also predicted clinical disease activity and correlated highly with FC. Further investigation of the role of CHI3L1 is required.
粪便钙卫蛋白(FC)、几丁质酶3样-1蛋白(CHI3L1)、S100A12和骨保护蛋白(OPG)是肠道炎症的生物标志物。这项横断面研究旨在评估克罗恩病(CD)儿童队列中的这些生物标志物,并将其与其他疾病活动指标进行比较。采用酶联免疫吸附法测定CD患儿粪便中FC、CHI3L1、S100A12和OPG。测量血清炎症标志物并计算儿童CD疾病活动指数(PCDAI)评分。报告了一个亚组的CD简易内镜评分(SES-CD),该亚组接受了与粪便样本相对应的回结肠镜检查。招募了65名儿童。临床缓解期儿童的FC和CHI3L1水平低于活动性疾病儿童(FC:277 vs.1648µg/g,p=0.012;CHI3L1:23 vs.227 ng/g,p=0.013)。临床活动性或非活动性孤立性回肠CD患者的FC水平不同。尽管FC和CHI3R1水平强相关(r=0.83),但粪便标志物与血清标志物均无良好相关性。只有FC和OPG与SES-CD评分相关(r分别为0.57和0.48)。总之,FC与内镜和临床疾病活动相关,是区分活动性和非活动性回肠CD的唯一生物标志物。CHI3L1也预测了临床疾病活动,并与FC高度相关。需要进一步研究CHI3L1的作用。
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引用次数: 1
Prognostic Impact of TP53 Mutations and Tumor Mutational Load in Colorectal Cancer 结直肠癌中TP53突变和肿瘤突变负荷对预后的影响
Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-08-02 DOI: 10.3390/gidisord4030016
V. Ho, L. Chung, Stephanie H. Lim, Yafeng Ma, Bin Wang, V. Lea, Askar Abubakar, Weng Ng, Mark Lee, T. Roberts, W. Chua, C. S. Lee
The DNA damage response (DDR) is critical for maintaining genome stability, and abnormal DDR—resulting from mutations in DNA damage-sensing and repair proteins—is a hallmark of cancer. Here, we aimed to investigate the predictive power of DDR gene mutations and the tumor mutational load (TML) for survival outcomes in a cohort of 22 rectal cancer patients who received pre-operative neoadjuvant therapy. Univariate analysis revealed that TML-high and TP53 mutations were significantly associated with worse overall survival (OS) with TML-high retaining significance in multivariate analyses. Kaplan–Meier survival analyses further showed TML-high was associated with worse disease-free (p = 0.036) and OS (p = 0.024) results in our patient cohort. A total of 53 somatic mutations were identified in 22 samples with eight (36%) containing mutations in DDR genes, including ATM, ATR, CHEK2, MRE11A, RAD50, NBN, ERCC2 and TP53. TP53 was the most frequently mutated gene, and TP53 mutations were significantly associated with worse OS (p = 0.023) in Kaplan–Meier survival analyses. Thus, our data indicate that TML and TP53 mutations have prognostic value for rectal cancer patients and may be important independent biomarkers for patient management. This suggests that prognostic determination for rectal cancer patients receiving pre-operative neoadjuvant therapy should include consideration of the initial TML and tumor genetic status.
DNA损伤反应(DDR)对于维持基因组稳定性至关重要,由DNA损伤敏感和修复蛋白突变引起的异常DDR是癌症的标志。在此,我们旨在研究DDR基因突变和肿瘤突变负荷(TML)对22名接受术前新辅助治疗的癌症患者生存结果的预测能力。单变量分析显示,TML高和TP53突变与较差的总生存率(OS)显著相关,TML在多变量分析中具有高保留意义。Kaplan-Meier生存率分析进一步表明,在我们的患者队列中,TML高与更差的无病(p=0.036)和OS(p=0.024)结果相关。在22个样本中共鉴定出53个体细胞突变,其中8个(36%)含有DDR基因突变,包括ATM、ATR、CHEK2、MRE11A、RAD50、NBN、ERCC2和TP53。TP53是最常见的突变基因,在Kaplan–Meier生存分析中,TP53突变与OS恶化显著相关(p=0.023)。因此,我们的数据表明,TML和TP53突变对癌症患者具有预后价值,可能是患者管理的重要独立生物标志物。这表明接受术前新辅助治疗的癌症患者的预后判断应包括考虑初始TML和肿瘤遗传状况。
{"title":"Prognostic Impact of TP53 Mutations and Tumor Mutational Load in Colorectal Cancer","authors":"V. Ho, L. Chung, Stephanie H. Lim, Yafeng Ma, Bin Wang, V. Lea, Askar Abubakar, Weng Ng, Mark Lee, T. Roberts, W. Chua, C. S. Lee","doi":"10.3390/gidisord4030016","DOIUrl":"https://doi.org/10.3390/gidisord4030016","url":null,"abstract":"The DNA damage response (DDR) is critical for maintaining genome stability, and abnormal DDR—resulting from mutations in DNA damage-sensing and repair proteins—is a hallmark of cancer. Here, we aimed to investigate the predictive power of DDR gene mutations and the tumor mutational load (TML) for survival outcomes in a cohort of 22 rectal cancer patients who received pre-operative neoadjuvant therapy. Univariate analysis revealed that TML-high and TP53 mutations were significantly associated with worse overall survival (OS) with TML-high retaining significance in multivariate analyses. Kaplan–Meier survival analyses further showed TML-high was associated with worse disease-free (p = 0.036) and OS (p = 0.024) results in our patient cohort. A total of 53 somatic mutations were identified in 22 samples with eight (36%) containing mutations in DDR genes, including ATM, ATR, CHEK2, MRE11A, RAD50, NBN, ERCC2 and TP53. TP53 was the most frequently mutated gene, and TP53 mutations were significantly associated with worse OS (p = 0.023) in Kaplan–Meier survival analyses. Thus, our data indicate that TML and TP53 mutations have prognostic value for rectal cancer patients and may be important independent biomarkers for patient management. This suggests that prognostic determination for rectal cancer patients receiving pre-operative neoadjuvant therapy should include consideration of the initial TML and tumor genetic status.","PeriodicalId":73131,"journal":{"name":"Gastrointestinal disorders (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45375231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
期刊
Gastrointestinal disorders (Basel, Switzerland)
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