gastrointestinal system

胃肠系统
  • 文章类型: Journal Article
    已经建立了人类胃肠道系统的微流体类器官芯片模型,以重建足够的微环境来研究生理学和病理生理学。为了寻找更多的模拟系统和成本更低的药物筛选或基础研究模型,胃肠道系统类器官芯片(GOoC)已成为有希望的临床前体外模型。这一进展是建立在生物打印等几种技术的最新发展基础上的,微流体,和类器官研究。在这篇综述中,我们将重点关注以下健康和疾病模型:人类芯片上的微生物组及其与胃病理生理学的相关性上升;胃芯片;肝脏芯片;胰腺芯片;小肠,结肠和结肠直肠癌类器官芯片和多器官芯片。与设计相关的当前发展,持有一个或多个“器官”的能力及其挑战,微流控功能,本文概述了细胞来源以及它们是否用于测试药物。重要的是,他们在精准医学领域的药物开发和卓越的临床翻译方面的贡献,FDA批准的型号,作者还讨论了类器官芯片技术在药物研发成本方面的影响。
    Microfluidic organs and organoids-on-a-chip models of human gastrointestinal systems have been established to recreate adequate microenvironments to study physiology and pathophysiology. In the effort to find more emulating systems and less costly models for drugs screening or fundamental studies, gastrointestinal system organoids-on-a-chip have arisen as promising pre-clinicalin vitromodel. This progress has been built on the latest developments of several technologies such as bioprinting, microfluidics, and organoid research. In this review, we will focus on healthy and disease models of: human microbiome-on-a-chip and its rising correlation with gastro pathophysiology; stomach-on-a-chip; liver-on-a-chip; pancreas-on-a-chip; inflammation models, small intestine, colon and colorectal cancer organoids-on-a-chip and multi-organoids-on-a-chip. The current developments related to the design, ability to hold one or more \'organs\' and its challenges, microfluidic features, cell sources and whether they are used to test drugs are overviewed herein. Importantly, their contribution in terms of drug development and eminent clinical translation in precision medicine field, Food and Drug Administration approved models, and the impact of organoid-on-chip technology in terms of pharmaceutical research and development costs are also discussed by the authors.
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  • 文章类型: Journal Article
    植物多酚是天然抗氧化剂和益生元的丰富来源。摄入后,大多数多酚在肠道中被吸收,并与肠道微生物群和细菌发酵产生的调节代谢物相互作用,例如短链脂肪酸(SCFA)。膳食多酚通过调节肠道微生物的免疫调节作用,抑制包括结肠癌在内的各种疾病的病因和发病机制,结直肠癌,炎症性肠病(IBD)和结肠炎。Foodomics是一种新型的高通量分析方法,广泛应用于食品和营养研究。结合基因组学,转录组学,蛋白质组学,代谢组学,并整合了多组学技术。在这次审查中,我们概述了从天然食品中识别活性多酚成分的foodomics技术,以及基于foodomics方法的多酚的胃肠道保护作用的总结。此外,我们严格评估了应用foodomics技术研究多酚对胃肠道(GI)系统的保护作用的局限性.最后,我们概述了foodomics技术的未来方向,以研究多酚的胃肠道保护作用。Foodomics基于多个分析平台和用于基因组学的数据处理的组合,转录组学,蛋白质组学和代谢组学研究,提供了丰富的数据,并在分子水平上更全面地了解了多酚与胃肠道之间的相互作用。这一贡献为进一步探索多酚对GI系统的保护机制提供了基础。
    Plant polyphenols are rich sources of natural anti-oxidants and prebiotics. After ingestion, most polyphenols are absorbed in the intestine and interact with the gut microbiota and modulated metabolites produced by bacterial fermentation, such as short-chain fatty acids (SCFAs). Dietary polyphenols immunomodulatory role by regulating intestinal microorganisms, inhibiting the etiology and pathogenesis of various diseases including colon cancer, colorectal cancer, inflammatory bowel disease (IBD) and colitis. Foodomics is a novel high-throughput analysis approach widely applied in food and nutrition studies, incorporating genomics, transcriptomics, proteomics, metabolomics, and integrating multi-omics technologies. In this review, we present an overview of foodomics technologies for identifying active polyphenol components from natural foods, as well as a summary of the gastrointestinal protective effects of polyphenols based on foodomics approaches. Furthermore, we critically assess the limitations in applying foodomics technologies to investigate the protective effect of polyphenols on the gastrointestinal (GI) system. Finally, we outline future directions of foodomics techniques to investigate GI protective effects of polyphenols. Foodomics based on the combination of several analytical platforms and data processing for genomics, transcriptomics, proteomics and metabolomics studies, provides abundant data and a more comprehensive understanding of the interactions between polyphenols and the GI tract at the molecular level. This contribution provides a basis for further exploring the protective mechanisms of polyphenols on the GI system.
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  • 文章类型: Journal Article
    2019年冠状病毒病(COVID-19),由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起,是历史上最具破坏性的流行病之一。SARS-CoV-2已经感染了全球超过1亿人,导致超过350万人死亡。最初,SARS-CoV-2感染的临床症状被认为仅限于呼吸系统。然而,进一步的研究表明,SARS-CoV-2还可以影响多个其他器官,包括胃肠道和中枢神经系统。SARS-CoV-2感染后胃肠道和神经系统表现的数量迅速增加。最重要的是,感染SARS-CoV-2的患者通常在胃肠道和神经系统中表现出共病症状。本文旨在探讨SARS-CoV-2神经侵袭的病理生理机制。SARS-CoV-2可能通过侵入胃肠道系统而影响神经系统。希望本综述能为临床治疗SARS-CoV-2感染的神经系统症状提供新的思路,为制定防治策略提供参考。
    Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most devastating pandemics in history. SARS-CoV-2 has infected more than 100 million people worldwide, leading to more than 3.5 million deaths. Initially, the clinical symptoms of SARS-CoV-2 infection were thought to be restricted to the respiratory system. However, further studies have revealed that SARS-CoV-2 can also afflict multiple other organs, including the gastrointestinal tract and central nervous system. The number of gastrointestinal and neurological manifestations after SARS-CoV-2 infection has been rapidly increasing. Most importantly, patients infected with SARS-CoV-2 often exhibit comorbid symptoms in the gastrointestinal and neurological systems. This review aims to explore the pathophysiological mechanisms of neuroinvasion by SARS-CoV-2. SARS-CoV-2 may affect the nervous system by invading the gastrointestinal system. We hope that this review can provide novel ideas for the clinical treatment of the neurological symptoms of SARS-CoV-2 infection and references for developing prevention and treatment strategies.
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  • 文章类型: Journal Article
    尽管替莫唑胺已被广泛用于治疗各种肿瘤,缺乏关于替莫唑胺毒性特征的大队列研究。分析了使用替莫唑胺治疗的患者的毒性特征和相关因素。
    2008年1月至2019年12月华中科技大学附属协和医院接受替莫唑胺治疗的患者。回顾性分析含替莫唑胺方案治疗患者的临床资料。采用单因素卡方检验和多因素logistic回归分析确定与毒性发生相关的因素。
    在1057名接受替莫唑胺治疗的患者中,我们的分析包括922例患者。在922名患者中,484例患者(52.5%)出现毒性反应。单因素分析显示放疗,化疗周期,化疗方案,临床分期与替莫唑胺治疗期间的毒副反应显著相关(P<0.05)。化疗方案,化疗周期,临床分期与总的毒副反应发生显著相关(P<0.05)。化疗方案,化疗周期,临床分期与血液系统的毒性有关,而性别,年龄,临床诊断,临床分期与胃肠道毒性有关(P<0.05)。临床诊断,化疗方案,年龄与肝毒性相关(P<0.05)。
    在接受含有替莫唑胺的方案的患者中,毒性是常见的。临床医生应该意识到与毒性相关的因素,以尽量减少毒性的影响。
    OBJECTIVE: Although temozolomide has been extensively used to treat various tumors, there is a lack of large-cohort studies on temozolomide\'s toxicity profile. The toxicity profiles and associated factors in patients treated with temozolomide-containing regimens were analyzed.
    METHODS: Patients treated with temozolomide-containing regimens in the Affiliated Union Hospital of Huazhong University of Science and Technology from January 2008 to December 2019 were included. A retrospective analysis of the clinical data of patients treated with temozolomide-containing regimens was performed. Univariate chi-square test and multivariate logistic regression analysis were employed to identify factors associated with the occurrence of toxicities.
    RESULTS: Among the 1057 patients received temozolomide-containing regimens, 922 patients were included in our analyses. Of the 922 patients, 484 patients (52.5%) experienced toxicities. Univariate analysis revealed that radiotherapy, chemotherapy cycle, chemotherapy regimen, and clinical stage were significantly associated with the toxicity during temozolomide treatment (P < 0.05). The chemotherapy regimen, chemotherapy cycle, and clinical stage were significantly associated with the overall occurrence of toxicities (P < 0.05). A chemotherapy regimen, chemotherapy cycle, and clinical stage were associated with the hematological system\'s toxicities, whereas gender, age, clinical diagnosis, and clinical stage were related to gastrointestinal toxicities (P < 0.05). Clinical diagnosis, chemotherapy regimen, and age were associated with liver toxicity (P < 0.05).
    CONCLUSIONS: Toxicities are common among patients receiving temozolomide-containing regimens. Clinicians should be aware of factors associated with toxicities to minimize the impact of the toxicity.
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  • 文章类型: Journal Article
    简介:第一代生物可吸收支架(BRS)具有大的支柱轮廓,以弥补生物可吸收聚合物材料的径向强度不足,导致支架血栓形成率高于常规药物洗脱支架。提高临床安全性和有效性,新一代BRS通过优化结构设计进行了改进,生物可吸收聚合物材料的后处理,或改变生物可吸收的金属合金。涵盖的领域:这篇综述总结了从第一代BRS中吸取的教训,更新了在长期和生物可吸收金属合金基设备上评估ABSORB生物可吸收血管支架的试验的临床结果,并检查STEMI患者BRS治疗的近期结果。这篇综述还概述了七个亚洲制造的BRS的当前临床数据,以及BRS在其他临床领域的扩展应用。专家意见:第一代BRS的缺点需要通过使用新材料和技术的下一代支架来解决。临床研究,包括随机对照试验,需要进一步评估BRS在冠状动脉疾病中的应用。BRS创新应用于外周动脉和胃肠道的令人鼓舞的结果支持了BRS技术的其他潜在临床应用。
    Introduction: The first-generation bioresorbable scaffolds (BRSs) had a large strut profile to compensate for the insufficient radial strength of bioresorbable polymer materials, resulting in higher scaffold thrombosis rates than conventional drug-eluting stents. To improve the clinical safety and efficacy, the new generation BRSs have been improved by optimal structure design, post-processing of bioresorbable polymer materials, or altering bioresorbable metallic alloys.Areas covered: This review summarizes the lessons learned from the first-generation BRS, updates the clinical outcomes of trials evaluating ABSORB bioresorbable vascular scaffold at long-term and bioresorbable metallic alloy-based devices, and examines recent outcomes of BRS treated in STEMI patients. This review also provides an overview of the current clinical data of seven BRSs manufactured in Asia, and of the BRSs extended application in other clinical arenas.Expert opinion: Drawbacks of the first-generation BRSs need to be addressed by the next generation of these stents with novel materials and technologies. Clinical research, including randomized controlled trials, are required to further evaluate BRSs application in coronary artery disease. The encouraging results of BRSs innovation applied in the peripheral arteries and gastrointestinal tracts support other potential clinical applications of BRS technology.
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  • 文章类型: Journal Article
    The human pathogenic yeast genus Malassezia may be an etiological agent of skin disorders and has received considerable attention from dermatologists in recent years. To investigate the different susceptibilities of Malassezia species to four antifungal drugs, we isolated a total of 244 Malassezia strains and identified six species of Malassezia from patients with clinical skin diseases. The minimum inhibitory concentration (MIC) of the four antifungal drugs was obtained by comparing the susceptibility of the isolated Malassezia strains to four antifungal drugs (ketoconazole (KTZ), itraconazole (ITZ), fluconazole (FLC) and amphotericin B (Am B)). We demonstrated that M. furfur, M. sympodialis, M. pachydermatis and M. globosa are the most common Malassezia species in the three skin diseases. The MICs of KTZ, ITZ, FLC and Am B against M. furfur, M. sympodialis, M. pachydermatis and M. globosa ranged from 0.03 - 16 mg/L, 0.03 - 2.0 mg/L, 0.03 - 8 mg/L, and 13 - 64 mg/L, respectively. The sensitivities of Malassezia to the four antifungal drugs from high to low were ITZ ≥ KTZ > Am B > FLC. The susceptibilities of the various Malassezia species to the four antifungal drugs were different, and the susceptibility of M. furfur to KTZ was significantly different from those of the three skin diseases (pityriasis versicolor, Malassezia folliculitis and seborrheic dermatitis). Our results suggested that the MIC analysis of the four antifungal drugs would be helpful in preventing drug resistance in the clinical screening of Malassezia and choosing better antifungal drugs to treat Malassezia-associated skin diseases.
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  • 文章类型: Journal Article
    Objective: To investigate the etiology, treatment method and prevention of gastrointestinal complications(GCs) after endovascular and open repair of abdominal aortic aneurysm (AAA). Methods: The clinical data of 716 cases who were diagnosed as AAA and underwent endovascular(EVAR) or open repair (OR) from Department of Vascular Surgery, Beijing Anzhen Hospital, Capital Medical University April 2009 to March 2017 were collected and analyzed retrospectively. There were 608 males (84.9%)and 108 females(15.1%), aging of 69.4 years (range: 52-86 years). There were 539 cases(75.3%) underwent EVAR and 177 cases(24.7%) underwent OR. The morbidity of GCs and mortality of GCs, such as acute pancreatitis, cholecystitis, ischemic colitis, intestinal obstruction and peptic ulcer, between EVAR and OR group were compared. The treatment of the GCs and the prognosis of the patients were reported. Results: The morbidity of GCs in EVAR and OR group were 4.6%(25/539)and 35.0%(62/177), respectively. There were 10 cases and 28 cases suffering from acute pancreatitis in EVAR and OR group, respectively; 4 cases and 6 cases suffering from cholecystitis in the two groups; 6 cases and 13 cases suffering from ischemic colitis in the two groups; 5 cases suffering from intestinal obstruction in OR group; 5 cases and 10 cases suffering from peptic ulcer in the two groups. Two patients died in EVAR group, and the peri-operative mortality was 0.37%, one died of ischemic colitis with acute myocardial infarction, the other died of ischemic colitis with septic shock. Six patients died in OR group, and the peri-operative mortality was 3.39%, two patients died of acute pancreatitis with intestinal necrosis, one patient died of cholangitis with peritonitis and septic shock, three patients died of ischemic colitis with acute renal failure or septicemia. Conclusions: The etiology of peri-operative GCs after AAA repair may include inferior mesenteric artery occlusion or ligation, pancreas injury, organ hypoperfusion and so on.
    目的: 探讨腹主动脉瘤(AAA)腔内修复(EVAR)及开放修复(OR)术后消化系统并发症的发生原因、处理方法和预防措施。 方法: 对首都医科大学附属北京安贞医院血管外科2009年4月至2017年3月诊治的716例AAA患者的临床资料进行回顾性分析。716例AAA患者中,男性608例(84.9%),女性108例(15.1%),年龄69.4岁(范围:52~86岁);行EVAR术539例(75.3%),行OR术177例(24.7%)。统计分析EVAR组和OR组患者消化系统并发症(急性胰腺炎、胆囊炎、缺血性结肠炎、肠梗阻、消化道溃疡)的发生及治疗转归情况。 结果: EVAR组和OR组患者术后消化系统并发症总体发生率分别为4.6%(25/539)和35.0%(62/177),其中急性胰腺炎分别为10例和28例,胆囊炎分别为4例和6例,缺血性结肠炎分别为6例和13例,肠梗阻分别为0例和5例,消化道溃疡分别为5例和10例。围手术期有8例患者死亡,其中EVAR组死亡2例(0.37%),死因分别为术后缺血性结肠炎合并急性心肌梗死1例、缺血性结肠炎合并感染中毒性休克1例;OR组死亡6例(3.39%),死因分别为术后急性胰腺炎合并肠坏死2例、胆管炎继发腹膜炎并发感染中毒性休克1例、缺血性结肠炎合并急性肾功能衰竭或败血症3例。 结论: AAA术后消化系统并发症的发生多与术中封盖或结扎肠系膜下动脉、胰腺损伤、器官低灌注等因素有关。.
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  • 文章类型: Journal Article
    药物的口服给药是方便的并且显示出良好的依从性,但是它可以受到胃肠(GI)系统中的许多因素的影响。食物的消耗是影响GI系统并因此影响药物吸收的主要因素之一。这项研究的目的是建立一个机械的胃肠道吸收模型,以解释食物对非诺贝特药代动力学(PK)的影响。专注于食物类型和卡路里含量。
    非诺贝特PK研究的临床数据涉及三种不同的条件(禁食,使用标准膳食和高脂肪膳食)。采用非线性混合效应建模方法建立模型。评估线性和非线性效应以解释食物摄入对药物吸收的影响。同样,为了解释由于食物影响而导致的药物胃排空时间的变化。
    在进食后的前6.94h,胃排空率增加了61.7%。十二指肠中卡路里的增加增加了在进食条件下药物的吸收速率常数(标准餐=16.5%,高脂肪餐=21.8%)与禁食条件相比。最终模型显示出良好的预测能力和精度。
    成功开发了用于定量评估食物对非诺贝特吸收的影响的机械GI吸收模型,并获得了可接受的参数。基于机制的非诺贝特PK模型可以通过食物类型和卡路里含量来量化食物对药物吸收的影响。
    Oral administration of drugs is convenient and shows good compliance but it can be affected by many factors in the gastrointestinal (GI) system. Consumption of food is one of the major factors affecting the GI system and consequently the absorption of drugs. The aim of this study was to develop a mechanistic GI absorption model for explaining the effect of food on fenofibrate pharmacokinetics (PK), focusing on the food type and calorie content.
    Clinical data from a fenofibrate PK study involving three different conditions (fasting, standard meals and high-fat meals) were used. The model was developed by nonlinear mixed effect modeling method. Both linear and nonlinear effects were evaluated to explain the impact of food intake on drug absorption. Similarly, to explain changes in gastric emptying time for the drug due to food effects was evaluated.
    The gastric emptying rate increased by 61.7% during the first 6.94 h after food consumption. Increased calories in the duodenum increased the absorption rate constant of the drug in fed conditions (standard meal = 16.5%, high-fat meal = 21.8%) compared with fasted condition. The final model displayed good prediction power and precision.
    A mechanistic GI absorption model for quantitatively evaluating the effects of food on fenofibrate absorption was successfully developed, and acceptable parameters were obtained. The mechanism-based PK model of fenofibrate can quantify the effects of food on drug absorption by food type and calorie content.
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  • 文章类型: Journal Article
    Objective: To observe the therapeutic efficacy of alanyl glutamine injection on patients with gastrointestinal function obstacle caused by severe phorate poisoning. Methods: A total of 80 eligible patients with gastrointestinal function obstacle caused by severe phorate poisoning were randomly divided into the control group (n=40) and treatment group (n=40) . The control group was treated with the conventional therapy, which included forbidden diet, atropine, pralidoxime iodide, anti-inflammatory, albumin infusion, ω-3 fish oil fat emulsion, protection of organs function, blood perfusion, and Fat Emulsion, Amino Acids (17) and Glucose Injection. The treatment group was treated with alanyl glutamine injection plus the conventional therapy. To observe the time of recovering to normal of gastrointestinal function between the two groups, compared the AChE activity and changes of prealbumin, albumin and total protein of the two groups respectively. Furthermore, the total atropine dosage, the total pralidoxime iodide dosage and ICU stay time between the two groups were also compared. Results: The gastrointestinal function recovery time of patients in the treatment group was less than the control group, the difference was statistically significant (P<0.05) . From the third day of treatment, the serum cholinesterase activity of the treatment group was higher than the control group, the difference was statistically significant (P<0.05) . On the 5th day and 10th day of the treatment, the prealbumin, albumin and total protein of the treatment group were significantly higher than these indexes of the control group in the same period, the difference were statistically significant (P<0.05) . The total atropine dosage, the total pralidoxime iodide dosage and ICU stay time in the treatment group were lower than the control group, the difference were statistically significant (P<0.05) . Conclusion: Alanyl glutamine injection has a great therapeutic effect for gastrointestinal function obstacle patients caused by severe phorate poisoning.
    目的: 观察丙氨酰谷氨酰胺注射液治疗重度甲拌磷农药中毒致胃肠功能障碍患者的疗效。 方法: 将80例符合研究条件的重度甲拌磷农药中毒致胃肠功能障碍患者随机分为对照组(40例)和治疗组(40例)。对照组给予禁饮食、阿托品、碘解磷定、抗炎、白蛋白、脂肪乳氨基酸葡萄糖注射液、ω-3鱼油脂肪乳注射液、血液灌流等综合治疗。治疗组在对照组治疗的基础上加用丙氨酰谷氨酰胺注射液。比较两组患者胃肠道功能恢复正常的时间,两组患者胆碱酯酶活力、前白蛋白、白蛋白及总蛋白的变化,解毒药物阿托品及碘解磷定的总用量,以及两组患者入住重症监护室的时间。 结果: 治疗组患者胃肠功能障碍恢复至正常的时间少于对照组,差异有统计学意义(P<0.05)。给予丙氨酰谷氨酰胺注射液治疗的第3、5、7、10天,治疗组患者的胆碱酯酶活力均明显高于对照组,差异有统计学意义(P<0.05)。给予丙氨酰谷氨酰胺注射液治疗的第5和10天,治疗组患者的前白蛋白、白蛋白及总蛋白均高于同期对照组指标,差异均有统计学意义(P<0.05)。治疗组患者的解毒药物总用量(阿托品、碘解磷定)以及在重症监护室的住院时间均低于对照组,差异有统计学意义(P<0.05)。 结论: 丙氨酰谷氨酰胺注射液对重度甲拌磷农药中毒致胃肠功能障碍患者有良好的治疗效果。.
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