Spatial Distribution of Endogenous Tissue Protease Activity in Gastric Carcinoma Mapped by MALDI Mass Spectrometry Imaging

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Highlights

• •New MALDI MS imaging sample preparation workflow reveals tissue protease activity.
• •Differential time- and inhibitor concentration-dependence confirm active proteases.
• •Mouse gastric tumor displays high protease activity compared to surrounding tissue.
• •Proteomic data and biochemical protease activity assay support MALDI MSI results.

     

Tracking gastrointestinal nematode risk on cattle farms through pasture contamination mapping

Gastrointestinal nematode (GIN) parasites in grazing cattle are a major cause of production loss and their control is increasingly difficult due to anthelmintic resistance and climate change. Rotational grazing can support control and decrease reliance on chemical intervention, but is often complex due to the need to track grazing periods and infection levels, and the effect of weather on larval availability. In this paper, a simulation model was developed to predict the availability of infective larvae of the bovine GIN, Ostertagia ostertagi, at the level of individual pastures. The model was applied within a complex rotational grazing system and successfully reproduced observed variation in larval density between fields and over time. Four groups of cattle in their second grazing season (n = 44) were followed throughout the temperate grazing season with regular assessment of GIN faecal egg counts, which were dominated by O. ostertagi, animal weight and recording of field rotations. Each group of cattle was rotationally grazed on six group-specific fields throughout the 2019 grazing season. Maps and calendars were produced to illustrate the change in pasture infectivity (density of L3 on herbage) across the 24 separate grazing fields. Simulations predicted differences in pasture contamination levels in relation to the timing of grazing and the return period. A proportion of L3 was predicted to persist on herbage over winter, declining to similar intensities across fields before the start of the following grazing season, irrespective of contamination levels in the previous year. Model predictions showed good agreement with pasture larval counts. The model also simulated differences in seasonal pasture infectivity under rotational grazing in systems that differed in temperature and rainfall profiles. Further application could support individual farm decisions on evasive grazing and refugia management, and improved regional evaluation of optimal grazing strategies for parasite control. The integration of weather and livestock movement is inherent to the model, and facilitates consideration of climate change adaptation through improved disease control.     

Genomic signatures of selection associated with benzimidazole drug treatments in Haemonchus contortus field populations

Genome-wide methods offer a powerful approach to detect signatures of drug selection. However, limited availability of suitable reference genomes and the difficulty of obtaining field populations with well-defined, distinct drug treatment histories mean there is little information on the signatures of selection in parasitic nematodes and on how best to detect them. This study addresses these knowledge gaps by using field populations of Haemonchus contortus with well-defined benzimidazole treatment histories, leveraging a recently completed chromosomal-scale reference genome assembly. We generated a panel of 49,393 genomic markers to genotype 20 individual adult worms from each of four H. contortus populations: two from closed sheep flocks with an approximate 20 year history of frequent benzimidazole treatment, and two populations with a history of little or no treatment. Sampling occurred in the same geographical region to limit genetic differentiation and maximise the detection sensitivity. A clear signature of selection was detected on chromosome I, centred on the isotype-1 β-tubulin gene. Two additional, but weaker, signatures of selection were detected; one near the middle of chromosome I spanning 3.75 Mbp and 259 annotated genes, and one on chromosome II spanning a region of 3.3 Mbp and 206 annotated genes, including the isotype-2 β-tubulin locus. We also assessed how sensitivity was impacted by sequencing depth, worm number, and pooled versus individual worm sequence data. This study provides the first known direct genome-wide evidence for any parasitic nematode, that the isotype-1 β-tubulin gene is quantitatively the single most important benzimidazole resistance locus. It also identified two additional genomic regions that likely contain benzimidazole resistance loci of secondary importance. This study provides an experimental framework to maximise the power of genome-wide approaches to detect signatures of selection driven by anthelmintic drug treatments in field populations of parasitic nematodes.     

两种内镜手术对消化道神经内分泌肿瘤的切除效果及安全性评价

目的:探讨内镜下两种手术方法对消化道神经内分泌肿瘤的切除效果和安全性。方法:选取64例消化道神经内分泌肿瘤患者,随机分为A组和B组,每组各32例。A组接受内镜下黏膜切除术,B组接受内镜下黏膜剥离术。分析和比较两组所切除组织的病理学检查结果、手术时间、切除肿瘤的直径和厚度、治疗费用、住院时间、肿瘤完全切除率、垂直切缘阴性率以及并发症的发生率。结果:A组的手术时间为(8.95±1.63) min,治疗费用为(2127.70±468.31)元,均显著少于B组(P0.05);两组患者切除肿瘤直径和厚度、住院时间、垂直切缘阴性率对比差异均没有统计学意义(P0.05);B组的肿瘤完全切除率为93.75%,显著高于A组(P0.05);A组并发症发生率为3.13%,显著低于B组(P0.05)。结论:两种内镜下手术方式均可有效清除消化道神经内分泌肿瘤病灶。内镜下黏膜切除术的手术时间、费用及并发症的发生率更少低,而内镜下黏膜剥离术能够更彻底地清除肿瘤组织。     

全身麻醉下不同脑电双频指数对老年胃肠道恶性肿瘤患者应激反应、炎性因子和术后认知功能的影响

摘要 目的：观察全身麻醉下不同脑电双频指数（BIS）对老年胃肠道恶性肿瘤患者应激反应、炎性因子和术后认知功能的影响。方法：选择2020年10月-2021年4月在新疆医科大学附属肿瘤医院初诊的住院老年胃肠道恶性肿瘤患者,共98例。据随机数字表法分为浅麻醉组（n=49,BIS值45~55）和深麻醉组（n=49,BIS值30~40）。对比两组苏醒质量、应激反应、炎性因子、术后认知功能、血流动力学及不良反应。结果：浅麻醉组的苏醒时间、定向力恢复时间、气管拔管时间短于深麻醉组（P<0.05）。插管后即刻（T1）~术毕（T5）时间点,两组心率（HR）、平均动脉压（MAP）均下降后升高（P<0.05）。深麻醉组T1~T5时间点HR、MAP高于浅麻醉组（P<0.05）。手术开始2 h（T4）、拔管后60 min（T6）时间点,两组皮质醇（Cor）、促肾上腺皮质激素（ACTH）水平呈升高趋势,且浅麻醉组高于深麻醉组（P<0.05）。T4、T6时间点,两组白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平持续升高,但浅麻醉组低于深麻醉组（P<0.05）。深麻醉组的术后3 d、术后7 d 简明精神状态量表（MMSE）评分低于浅麻醉组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：全身麻醉下老年胃肠道恶性肿瘤患者BIS值范围30~40可维持更平稳的血流动力学,应激反应低,但是其对认知功能影响相对较大;BIS值在45~55之间时,患者苏醒快,炎性因子水平更低;临床应结合实际情况合理调控BIS值。     

胃康胶囊联合兰索拉唑肠溶胶囊对胃溃疡患者胃肠激素、炎症反应和T淋巴细胞亚群的影响

摘要 目的：观察胃康胶囊联合兰索拉唑肠溶胶囊治疗胃溃疡的疗效及对胃肠激素、炎症反应和T淋巴细胞亚群的影响。方法：选择2018年9月~2021年5月在中国人民解放军31694部队医院消化内科接受治疗的80例胃溃疡患者作为观察对象,根据信封抽签法分为对照组和观察组,各为40例。对照组患者接受兰索拉唑肠溶胶囊治疗,观察组患者接受胃康胶囊联合兰索拉唑肠溶胶囊治疗,连续治疗6周。对比两组临床疗效、幽门螺杆菌（Hp）根除率和溃疡愈合率,观察治疗期间不良反应发生情况,对比两组治疗前、治疗6周后的胃肠激素、血清炎症因子和T淋巴细胞亚群指标水平的变化。结果：观察组的临床总有效率较对照组高（P<0.05）。观察组的Hp根除率和溃疡愈合率均高于对照组（P<0.05）。治疗6周后,两组CD3⁺、CD4⁺、CD4⁺/CD8⁺较治疗前升高,CD8⁺ 较治疗前下降,且观察组的改善效果优于对照组（P<0.05）。治疗6周后,两组胃动素（MTL）水平较治疗前升高,胃泌素（GAS）水平较治疗前下降,且观察组的改善效果优于对照组（P<0.05）。治疗6周后,两组高迁移率族蛋白B1（HMGB1）、白介素-6（IL-6）、C反应蛋白（CRP）水平较治疗前下降,且观察组的改善效果优于对照组（P<0.05）。两组不良反应发生率对比无统计学差异（P>0.05）。结论：兰索拉唑肠溶胶囊联合胃康胶囊可提高胃溃疡患者的溃疡愈合率和Hp根除率,其作用机制可能与调节胃肠激素、炎症反应和T淋巴细胞亚群指标水平有关。     

PBL联合CBL教学方法在胃肠外科临床见习教学中的应用

目的:探讨PBL联合CBL教学模式在医学生胃肠外科见习教学中的应用效果.方法:选取50名2008级胃肠外科见习医学生作为研究对象,将其随机分成两组:实验组采用PBL联合CBL教学模式,对照组则仅采用传统LBL教学模式.通过出科考核及问卷调查两种方式评价胃肠外科见习教学效果.结果:显示PBL+ CBL组的考试成绩要明显优于LBL组,差异有统计学意义(P＜ 0.05),并且见习后的问卷调查结果提示学生对PBL+ CBL的教学模式满意度较高.结论:我们的研究结果表明PBL+ CBL双轨教学模式受到学生欢迎,在提高学生理论知识水平方面比LBL模式更为有效.     

Expression pattern of the homeotic gene Bapx1 during early chick gastrointestinal tract development

Regulation of the Bone Morphogenetic Protein (BMP) signaling pathway is essential for the normal development of vertebrate gastrointestinal (GI) tract, but also for the differentiation of the digestive mesenchymal layer into smooth muscles and submucosal layer. Different studies demonstrated that Bapx1 (for bagpipe homeobox homolog 1) negatively regulates the BMP pathway, but its precise expression pattern during the development and the differentiation of the GI tract mesenchyme actually remains to be examined. Here, we present the spatio-temporal expression profile of Bapx1 in the chick GI tract. We show that Bapx1 is first expressed in the undifferentiated mesenchyme of the gizzard and the colon. After the differentiation of the digestive mesenchyme, we found Bapx1 strongly expressed in the gizzard smooth muscle and in the submucosa layer of the colon. This expression pattern provides new insights into the roles of Bapx1 during the regionalization of the GI tract and the differentiation of the digestive mesenchyme of the colon and the stomach.     

四君子汤加减降低胃肠肿瘤患者术后复发转移的研究进展

胃肠道肿瘤已经成为我国的高发肿瘤,降低肿瘤的复发转移是目前研究的热点问题。四君子汤的应用在降低胃肠肿瘤患者术后复发转移中的确起到了重要的作用。本文检索了近10年国内外的相关文献,分别从中医理论的认识、临床研究、实验研究及药理研究等方面,总结四君子汤在胃肠肿瘤患者术后复发转移的防治方面的进展。     

肠道菌群与疾病关系的研究进展

人类肠道是一个多元化和充满活力的微生态系统,它的结构和功能成为目前生命科学和医学的研究热点。人类肠道拥有100万亿近1 000-1 150种细菌,在这个空间中它们与人类相互作用,对人类健康产生了巨大影响,其中有积极的作用,同时又伴随着潜在的威胁。本文详细论述了国内外关于肠道菌群与疾病关系的研究现状,益生菌对肠道菌群和健康的影响,以及研究肠道菌群的最新方法,为我国开展肠道微生物的研究提供部分参考,同时让人们更加了解肠道微生物对人类健康的影响。