A 3D-printable device allowing fast and reproducible longitudinal preparation of mouse intestines

Accurate and reproducible analysis of murine small and large intestinal tissue is key for preclinical models involving intestinal pathology.Currently,there is no easily ac-cessible,standardized method that allows researchers of different skill levels to con-sistently dissect intestines in a time-efficient manner.Here,we describe the design and use of the 3D-printed“Mouse Intestinal Slicing Tool”(MIST),which can be used to longitudinally dissect murine intestines for further analysis.We benchmarked the MIST against a commonly used procedure involving scissors to make a longitudinal cut along the intestines.Use of the MIST halved the time per mouse to prepare the intestines and outperformed alternative methods in smoothness of the cutting edge and overall reproducibility.By sharing the plans for printing the MIST,we hope to contribute a uniformly applicable method for saving time and increasing consistency in studies of the mouse gastrointestinal tract.

Immunological mechanisms and therapeutic targets of fatty liver diseases

Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and continuous inflammation promotes the progression of alcoholic steatohepatitis(ASH)and nonalcoholic steatohepatitis(NASH).Although both ALD and NAFLD are closely related to inflammation,their respective developmental mechanisms differ to some extent.Here,we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH.Multiple cell types in the liver,including macrophages,neutrophils,other immune cell types and hepatocytes,are involved in fatty liver disease inflammation.In addition,microRNAs(miRNAs),extracellular vesicles(EVs),and complement also contribute to the inflammatory process,as does intertissue crosstalk between the liver and the intestine,adipose tissue,and the nervous system.We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections.Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.

Type I interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization

Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.

经颈静脉肝内门体分流术后再入院率:14年的单中心诊疗经验

背景:经颈静脉肝内门体分流术(TIPS)常用于治疗门脉高压并发症。然而,关于TIPS术后再入院率的数据十分有限,而且尚无研究关注其再入院的原因。为此,本研究旨在明确本中心TIPS术后30天再入院率,并分析再入院的可能原因及预测因素。方法:我们通过Cleveland Clinic电子病案系统检索2004-2017年间接受初次TIPS治疗(采用聚四氟乙烯覆膜支架)的肝病患者,统计这些患者术后30天再入院率。采用单因素逻辑回归模型评估30天再入院的潜在预测因素。结果:566例TIPS患者纳入分析,其术后30天再入院率为36%。最常见的再入院原因包括意识模糊(48%)、感染(15%)、出血(11%)和液体过剩(7%)。终末期肝病模型(MELD)评分越高,再入院率越高(MELD评分每增加1分:OR¼1.06,95%CI:1.02–1.09,P¼0.001)。其他再入院的潜在预测因素(包括TIPS适应证)则未获本研究证实。结论:采用覆膜支架行TIPS术,其术后30天再入院率较高,且近半数的再入院是因为肝性脑病(一种已知的TIPS并发症)。未来应重点研发一些新的干预措施以降低TIPS再入院率。