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Performance of tacrolimus in hospitalized patients with steroid-refractory acute severe ulcerative colitis

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World Journal of Gastroenterology 2019年第13期25卷 1603-1617页

作者： Peter Hoffmann Cyrill Wehling Johannes Krisam Jan Pfeiffenberger Nina Belling Annika Gauss Department of Gastroenterology and Hepatology Heidelberg University Hospital institute of medical biometry and informatics University of Heidelberg

BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often *** the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases(IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently *** To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative *** We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018, and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side *** the majority of the 22 included patients(68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d(mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4%were discharged from the hospital under continued oral tacrolimus therapy. In36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 1

关键词： Acute severe ulcerative colitis Steroid-refractory Tacrolimus Rescue therapy Calcineurin inhibitor Inflammatory bowel disease Hospitalized

Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric medical Research Center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Prevalence and risk factors of nonalcoholic fatty liver disease in patients with inflammatory bowel diseases:A cross-sectional and longitudinal analysis

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World Journal of Gastroenterology 2020年第46期26卷 7367-7381页

作者： Peter Hoffmann Victoria Jung Rouven Behnisch Annika Gauss Department of Gastroenterology and Hepatology University Hospital HeidelbergHeidelberg 69120Germany institute of medical biometry and informatics University Hospital HeidelbergHeidelberg 69120Germany

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is common in the German population,with an even higher prevalence in inflammatory bowel disease *** To investigate the risk factors for NAFLD in inflammatory bowel disease *** This monocentric retrospective study with a cross-sectional and a longitudinal part included 694 *** criteria were diagnosed inflammatory bowel disease,age≥18 years,availability of at least one abdominal *** with infectious or suspected alcoholic fatty liver disease were *** was defined by increased echogenicity at liver *** characteristics,disease activity and medications were analyzed as potential risk *** influencing the course of NAFLD were identified by a generalized linear mixed *** Forty-eight percent of Crohn’s disease(CD)patients and 44%of ulcerative colitis patients suffered from *** occurrence was associated with greater age,hypertension and body mass index(BMI)in both groups,and with higher disease activity and dyslipidemia in CD.2467 ultrasound results were included in the longitudinal *** factors for NAFLD were age,BMI,higher disease activity,bowel resection(s),endoscopic activity and azathioprine use in CD;and BMI and endoscopic activity in ulcerative *** NAFLD was highly prevalent in this cohort of German inflammatory bowel disease *** risk increased mainly with rising age and *** analysis provides a rationale for non-invasive liver screening in inflammatory bowel disease patients.

关键词： Crohn’s disease Ulcerative colitis Inflammatory bowel disease Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Ultrasound

Predictors of functional benefit of hepatitis C therapy in a‘real-life’cohort

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World Journal of Gastroenterology 2018年第7期24卷 852-861页

作者： Niels Steinebrunner Kerstin Stein Catharina Sandig Thomas Bruckner Wolfgang Stremmel Anita Pathil Department of Internal Medicine IV University Hospital HeidelbergHeidelberg 69120Germany Department of Gastroenterology Hepatology and Infectious DiseasesUniversity Hospital of MagdeburgMagdeburg 39120Germany Department of medical biometry Institute of Medical Biometry and Informatics(IMBI)Heidelberg 69120Germany

AIM To define predictors of functional benefit of direct-acting antivirals(DAAs) in patients with chronic hepatitis C virus(HCV) infection and liver *** We analysed a cohort of 199 patients with chronic HCV genotype 1, 2, 3 and 4 infection involving previously treated and untreated patients with compensated(76%) and decompensated(24%) liver cirrhosis at two tertiary centres in Germany. Patients were included withtreatment initiation between February 2014 and August 2016. All patients received a combination regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional benefit were assessed in a univariable as well as multivariable model by binary logistic regression *** Viral clearance was achieved in 88%(175/199) of patients. Sustained virological response(SVR) 12 rates were as follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90%(n = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57%(n = 4); among 30 patients with genotype 3 infection the SVR 12 rate was 87%(n = 26); and among 6 patients with genotype 4 infection the SVR 12 rate was 67%(n = 4). Follow-up MELD scores were available for 179 patients. A MELD score improvement was observed in 37%(65/179) of patients, no change of MELD score in 41%(74/179) of patients, and an aggravation was observed in 22%(40/179) of patients. We analysed predictors of functional benefit from antiviral therapy in our patients beyond viral eradication. We identified the Child-Pugh score, the MELD score, the number of platelets and the levels of albumin and bilirubin as significant factors for functional *** Our data may contribute to the discussion of potential risks and benefits of antiviral therapy with individual patients infected with HCV and with advanced liver disease.

关键词： functional benefit direct acting antiviral hepatitis C cirrhosis real-life data

Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia

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World Journal of Gastroenterology 2018年第38期24卷 4393-4402页

作者： Franziska J Ammon Anna Kohlhaas Omar Elshaarawy Johannes Mueller Thomas Bruckner Christof Sohn Gabriele Fluhr Herbert Fluhr Sebastian Mueller Department of Obstetrics and Gynecology University of Heidelberg Department of Medicine and Center for Alcohol Research Liver Disease and NutritionSalem Medical CenterUniversity of Heidelberg institute of medical biometry und informatics University of Heidelberg

AIM To study liver stiffness(LS) during pregnancy and its association with complications during *** In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem medical Center. LS was measured using the Fibroscan device(Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women(controls) while preeclampsia and intrahepatic cholestasis of pregnancy(ICP) developed in 22 and 40 women, *** In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa(P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index(BMI). In women with pregnancy complications, LS was significantly higher as compared to controls(P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05(1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa(P < 0.001).CONCLUSION During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent noninvasive predictor.

关键词： Pregnancy Transient elastography Liver stiffness Pregnancy complications Hemolysis,elevated liver enzymes and low platelets syndrome Intrahepatic cholestasis of pregnancy Preeclampsia

Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical informatics institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational medical Center for Stem Cell Therapy and institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research institute of Intelligent Computing Zhejiang Lab Shanghai Research institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

Single-cell technologies: current and near future

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Science China Life Sciences 2025年第01期 1-4页

作者： Chenfei Wang Qi Liu Xiaohui Fan Tieliu Shi Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationOrthopedics DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational medical Center for Stem Cell Therapy and institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research institute of Intelligent Computing Zhejiang Lab Pharmaceutical informatics institute College of Pharmaceutical SciencesZhejiang University National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Key Laboratory of Advanced Theory and Application in Statistics and Data Science (MOE) School of StatisticsEast China Normal University

Single-cell technologies enable the indepth exploration of multiple biological hierarchies at the scale of individual cells,which have deepened our knowledge of cellular diversity, tissue organization, and overall organism function(Sun et al.,2024). In 2009, single-cell RNA sequencing(sc RNA-seq) was first developed as a powerful tool to dissect gene expression and uncover transcriptional *** the rapid advancement of technology, single-cell approaches have expanded to encompass other omics, such as genomics, epigenomics, proteomics,and metabolomics.

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The impact of AI: can a robot get into the University of Tokyo?

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National Science Review 2015年第2期2卷 135-136页

作者： Noriko H.Arai National institute of informatics

The ‘Todai Robot Project(Can a robot get into the University of Tokyo?)’ was initiated by the National institute of informatics(NII),the Japan’s only general academic research institution of informatics,in 2011 as ... 详细信息

关键词： can a robot get into the University of Tokyo The impact of AI

Modelling stratified forest attributes using optical/LiDAR features in a central European landscape

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International Journal of Digital Earth 2012年第2期5卷 106-132页

作者： Hooman Latifi Arne Nothdurft Christoph Straub Barbara Koch Department of Remote Sensing and Landscape Information Systems University of FreiburgTennenbacherstraßeFreiburgGermany Department of biometry and informatics Forest Research Institute Baden WurttembergWonnhaldestraßeFreiburgGermany

Improvements in the acquisition of three-dimensional(3D)information from the Airborne Laser Scanner(ALS)increase its applications for studying Earth’s *** use of ALS data in natural resource inventories is still in an experimental stage in central ***,a survey was completed in Germany,where plot-level features from LANDSAT Thematic Mapper and ALS data were *** automated process was developed for forest stratification using orthoimages.A genetic algorithm was applied for variable *** subsets of different sizes were employed for simultaneous predictions of structural forest attributes using the‘Random Forest’(RF)*** was assessed by leave-one-out cross-validations on bootstrap resample *** indicate that the stratification of forest notably improved the results of *** improvements were more obvious for the strata-related *** was enhanced as the number of selected variables ***,parsimonious models are still essentially required for practical *** RF errors were slightly greater than those from least squares regression,as the non-parametric methods do not share the same mix of error components as *** the combination of remote sensing and modelling,we conclude that our results are helpful for bridging the gap between regional earth observation and on-the-ground forest structure.

关键词： spatial prediction natural resource inventory ALS Digital Earth data fusion remote sensing