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Application of Global Leadership Initiative on Malnutrition criteria in patients with liver cirrhosis

Chinese Medical Journal 2024年第1期137卷 97-104页

作者： Minjie Jiang Juan Chen Muchen Wu Jing Wu Xiaotong Xu Juan Li Can Liu Yaping Zhao Xin Hua Qinghua Meng Department of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing 100069China Department of Medical Oncology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of Nutrition Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:The Global Leadership Initiative on Malnutrition(GLIM)criteria were published to build a global consensus on nutritional *** muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus ***,there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical *** study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition,as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic ***:This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1,2018,and February 28,2022,at Beijing You-An Hospital,Capital Medical *** patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography(CT)examination during hospitalization were included in the *** patients were randomly divided into a modeling group(cohort 1,667 patients)and a validation group(cohort 2,335 patients).In cohort 1,optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index(L3-SMI)were determined using receiver operating characteristic analyses against in-hospital mortality in different gender ***,patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002(NRS-2002),and malnutrition was diagnosed by GLIM ***,the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort *** logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical ***:The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female *** on the cut-off values,31.63%(68/215)of the male patients and 23.3%(28/120)of the female patients had CT-determ

关键词： Malnutrition Liver cirrhosis Sarcopenia Clinical outcomes GLIM criteria

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LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure

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Chinese Medical Journal 2024年第2期137卷 190-199页

作者： Muchen Wu Jing Wu Kai Liu Minjie Jiang Fang Xie Xuehong Yin Jushan Wu Qinghua Meng Department of Liver Disease Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of General Surgery Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex *** hypoglycemia is common in patients with ACLF and often predicts a worse *** evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of *** protease-1(LONP1)is a novel mediator of energy and glucose ***,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains ***:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury ***1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis *** histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ***:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver ***,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF ***,mitochondrial morphology was improved upon overexpression of ***,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 ***,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis ***

关键词： Acute-on-chronic liver failure Lon protease-1 Gluconeogenesis disturbance Mitochondrial dysfunction Metabolism

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Fasn involved in the nephrotoxicity induced by polystyrene nanoplastics and the intervention of melatonin through intestinal microbiota-mediated lipid metabolism disorder

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Nano Research 2024年第8期17卷 7365-7375页

作者： Huiwen Kang Danyang Huang Jiaru Jing Wei Zhang Lei Zhang Jingyu Wang Ziyan Liu Lin Han Ziyan Wang Lefeng Zhang Ai Gao Department of Occupational Health and Environmental Health School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key Laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China

Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still *** this study,in vivo(60μg/day,42 days)and in vitro(0.4μg/μL,24 h)exposure models of polystyrene nanoplastics(PS-NPs,80 nm)in mice and human kidney cortex proximal tubule epithelial cells(HK-2 cells)were established,*** study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice,which were related to lipid metabolism disorders mediated by intestinal ***-fatty acid synthase(Fasn)-docosahexaenoic acid(DHA)pathway may be one of the mechanisms of kidney injury in ***,we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders(represented by DHA)and affects Fasn *** conclusion,our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.

关键词： nanoplastics nephrotoxicity lipid metabolism fatty acid synthase(Fasn) melatonin

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Prevalence and clinical impact of sarcopenia in liver transplant recipients:A meta-analysis

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World Journal of Gastroenterology 2024年第8期30卷 956-968页

作者： Min-Jie Jiang Mu-Chen Wu Zhong-Hui Duan Jing Wu Xiao-Tong Xu Juan Li Qing-Hua Meng Department of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of Emergency Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

BACKGROUND The prevalence of sarcopenia in patients undergoing liver transplantation(LT)remains to be determined partly because of different diagnostic *** has recently been recognized as a new prognostic factor for predicting outcomes in LT *** To estimate the prevalence of sarcopenia and evaluate its clinical effect on LT *** This systematic search was conducted in PubMed,Web of Science,Embase,and Cochrane Library for original English-language articles that investigated the prevalence and influence of sarcopenia in patients undergoing LT from database inception to November 30,*** studies of the definition of sarcopenia that estimate sarcopenia prevalence and evaluate its effect on clinical outcomes and the risk of mortality were *** Twenty-five studies involving 7760 patients undergoing LT were *** pooled prevalence of sarcopenia in patients undergoing LT was 40.7%[95%confidence intervals(95%CI):32.1-49.6].The 1-,3-,and 5-year cumulative probab-ilities of post-LT survival in patients with preoperative sarcopenia were all lower than those without sarcopenia(P<0.05).Sarcopenia was associated with an increased risk of post-LT mortality in patients undergoing LT(adjusted hazard ratio:1.58;95%CI:1.21-2.07).Patients with preoperative sarcopenia had a longer intensive care unit stay,a high risk ratio of sepsis,and serious post-LT complications than those without *** Sarcopenia is prevalent in a substantial proportion of patients undergoing LT and is strongly and independently associated with higher a risk of mortality risk.

关键词： Sarcopenia Liver transplantation Mortality Clinical outcomes

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Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation

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Journal of Environmental Sciences 2024年第8期142卷 259-268页

作者： Shiyu He Jingran Wang Lihong Zhou Zhen Mao Xiaodan Zhang Jin Cai Peili Huang School of Public Health and Beijing Key Laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China

The environmental behavior of and risks associated with nanoplastics(NPs)have attracted considerable ***,compared to pristine NPs,environmental factors such as ultraviolet(UV)irradiation that lead to changes in the toxicity of NPs have rarely been *** evaluated the changes in morphology and physicochemical properties of polystyrene(PS)NPs before and after UV irradiation,and compared their hepatotoxicity in *** results showed that UV irradiation caused particle size reduction and increased the carbonyl index(CI)and negative charge on the particle ***-aged PS NPs(aPS NPs)could induce the generation of hydroxyl radicals(·OH),but also further promoted the generation of·OH in the Fenton reaction *** pathological damage was more severe in mice exposed to aPS NPs,accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein,alanine aminotransferase and aspartate aminotransferase *** addition,exposure to PS NPs and aPS NPs,especially aPS NPs,triggered oxidative stress and significantly damaged the antioxidant capacity of mice *** with PS NPs,exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways,especially glutathione *** research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of·OH,enhancing PS NPs-induced liver damage and metabolic *** study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

关键词： Polystyrene nanoplastics Ultraviolet-aged nanoplastics Metabolic pathway Metabolomics Hydroxyl radical

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Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1711-1725页

作者： Yingting Wu Jiaqi Xin Xinyu Li Ting Yang Yi Liu Yongsheng Zhao Wen Xie Mengxi Jiang Department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Department of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China

Drug repurposing offers an efficient approach to therapeutic *** this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal *** went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in *** with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy ***,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent *** results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor *** summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.

关键词： Lansoprazole Proton pump inhibitors Adipose thermogenesis Energy expenditure Metabolic syndrome PHOSPHO1 inhibitor Cannabinoid receptor signaling Drug repurposing

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Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An Department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell *** review summarizes the existing scRNA-seq technologies together with their strengths and *** applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune ***-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

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Three-phase Enriched Environment Improves Post-stroke Gait Dysfunction via Facilitating Neuronal Plasticity in the Bilateral Sensorimotor Cortex:A Multimodal MRI/PET Analysis in Rats

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Neuroscience Bulletin 2024年第6期40卷 719-731页

作者： Yun Lu Ziyue Lin Mingcong Li Yuming Zhuang Binbin Nie Jianfeng Lei Yuanyuan Zhao Hui Zhao School of Traditional Chinese Medicine Capital Medical UniversityBeijing100069China Beijing Key Lab of TCM Collateral Disease Theory Research Beijing100069China Beijing Engineering Research Center of Radiographic Techniques and Equipment Institute of High Energy PhysicsChinese Academy of SciencesBeijing100049China Medical Imaging Laboratory of Core Facility Center Capital Medical UniversityBeijing100069China

The three-phase Enriched Environment(EE)paradigm has been shown to promote post-stroke functional improvement,but the neuronal mechanisms are still *** this study,we applied a multimodal neuroimaging protocol combining magnetic resonance imaging(MRI)and positron emission tomography(PET)to examine the effects of post-ischemic EE treatment on structural and functional neuroplasticity in the bilateral sensorimotor *** were subjected to permanent middle cerebral artery *** motor function of the rats was examined using the DigiGait *** was applied to investigate the EE-induced structural modifications of the bilateral sensorimotor cortex.[^(18)F]-fluorodeoxyglucose PET was used to detect glucose *** oxygen level-dependent(BOLD)-functional MRI(fMRI)was used to identify the regional brain activity and functional connectivity(FC).In addition,the expression of neuroplasticity-related signaling pathways including neurotrophic factors(BDNF/CREB),axonal guidance proteins(Robo1/Slit2),and axonal growth-inhibitory proteins(NogoA/NgR)as well as downstream proteins(RhoA/ROCK)in the bilateral sensorimotor cortex were measured by Western *** results showed the three-phase EE improved the walking *** T2 mapping imaging and diffusion tensor imaging demonstrated that EE benefited structure integrity in the bilateral sensorimotor ***-MRI fused images showed improved glucose metabolism in the corresponding regions after EE ***,the BOLD-based amplitude of low-frequency fluctuations showed that EE increased spontaneous activity in the bilateral motor cortex and ipsilateral sensory *** addition,FC results showed increased sensorimotor connectivity in the ipsilateral hemisphere and increased interhemispheric motor cortical connectivity and motor cortical-thalamic connectivity following EE *** addition,a strong correlation was found between increased functional connectivity and improv

关键词： Enriched environment Gait function Neuronal plasticity Structural integrity Glucose metabolism Functional connectivity Microenvironmental molecules Axonogenesis

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Bioinformatics analysis and experimental validation of cystathionine-gamma-lyase as a potential prognosis biomarker in hepatocellular carcinoma

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BIOCELL 2024年第3期48卷 463-471页

作者： YANAN MA SHANSHAN WANG HUIGUO DING Department of Gastroenterology and Hepatology Beijing You’an Hospital Affiliated with Capital Medical UniversityBeijing100069China Beijing Institute of Hepatology Beijing You’an Hospital Affiliated with Capital Medical UniversityBeijing100069China

Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality *** cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain ***:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further conﬁrmed by RT-qPCR and immunohistochemistry assays in HCC ***,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC ***,the biological functions of CSE in HCC cells was assessed by CCK-8,ﬂow cytometry and Western ***:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal *** CSE mRNA expression was signiﬁcantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our *** univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC *** vitro experiments further explained that CSE might trigger HCC cell apoptosis by ***:In summary,the present study identiﬁed the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.

关键词： Hepatocellular carcinoma Cystathionine-gamma-lyase Hydrogen sulfide Prognosis Apoptosis

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Decabromodiphenyl ether induces the chromosome association disorders of spermatocytes and deformation failures of spermatids in mice

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Journal of Environmental Sciences 2024年第4期138卷 531-542页

作者： Jinglong Xue Xiangyang Li Yafei Chi Leqiang Gao Yue Zhang Yan Wang Moxuan Zhao Jialiu Wei Zhixiong Shi Xianqing Zhou Department of Toxicology and Hygienic Chemistry School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key Laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China Laboratory Animal Center Capital Medical UniversityBeijing 100069China Key Laboratory of Cardiovascular Epidemiology&Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

The environmental presence of decabromodiphenyl ether(BDE-209),which is toxic to the male reproductive system,is *** current study investigated its mechanism of toxicity in *** results showed,that BDE-209 induced DNA damage,decreased the expression of the promoter of meiosis spermatogenesis-and oogenesis-specific basic helix-loop-helix 1(Sohlh1),meiosis related-factors Lethal(3)malignant brain tumor like 2(L3MBTL2),PIWI-like protein 2(MILI),Cyclin-dependent kinase 2(CDK2),Cyclin A,synaptonemal complex protein 1(SYCP1)and synaptonemal complex protein 3(SYCP3),and caused spermatogenic cell apoptosis,resulting in a decrease in sperm quantity and ***,BDE-209 downregulated the levels of anaphase-promoting complex/cyclosome(APC/C),increased the expression of PIWI-like protein 1(MIWI)in the cytoplasm of elongating spermatids,and decreased the nuclear levels of RING finger protein 8(RNF8),ubiquitinated(ub)-H2A/ub-H2B,and Protamine 1(PRM1)/Protamine 2(PRM2),while increasing H2A/H2B nuclear levels in *** reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 *** results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of ***,the reduced expression of L3MBTL2 inhibited the formation of chromosomal synaptonemal complexes by depressing the expression of meiosis regulators affecting the meiotic progression and also inhibited histone ubiquitination preventing the replacement of histones by protamines,by preventing RNF8 from entering nuclei,which affected the evolution of spermatids into mature sperm.

关键词： BDE-209 Meiosis L3MBTL2 Sperm RNF8 Histone ubiquitination

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