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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 diagnosis.Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria.However,there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings.This 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 patients.Methods: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 University.Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography(CT)examination during hospitalization were included in the study.These 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 groups.Next,patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002(NRS-2002),and malnutrition was diagnosed by GLIM criteria.Additionally,the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1.Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results: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 patients.Based on the cut-off values,31.63%(68/215)of the male patients and 23.3%(28/120)of the female patients had CT-determined sarcopenia in cohort 2.The prevalence of GL

关键词： Malnutrition Liver cirrhosis Sarcopenia Clinical outcomes GLIM criteria

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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 worldwide.Although 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 elusive.Methods: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 samples.Furthermore,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally,the biological functions of CSE in HCC cells was assessed by CCK-8,ﬂow cytometry and Western blotting.Results:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was signiﬁcantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following 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 patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H2S.Conclusion: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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Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated HIV-1 DNA

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Chinese Medical Journal 2024年第6期137卷 729-736页

作者： Lin Yuan Zhiying Liu Xin Zhang Feili Wei Shan Guo Na Guo Lifeng Liu Zhenglai Ma Yunxia Ji Rui Wang Xiaofan Lu Zhen Li Wei Xia Hao Wu Tong Zhang Bin Su beijing Key Laboratory for HIV/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China beijing institute of hepatology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV persistence.Droplet digital polymerase chain reaction(ddPCR)can be used for absolute quantification without needing a standard curve.Here,we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods:The limit of detection,dynamic ranges,sensitivity,and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat(LTR)and human CD3 gene(for total HIV DNA)and ACH-2 cells(for integrated HIV DNA).Forty-two cases on stable suppressive antiretroviral therapy(ART)were assayed in total HIV DNA and integrated HIV DNA.Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive(CD4^(+))T-cell counts,CD8^(+)T-cell counts and CD4/CD8 T-cell ratio,respectively.The assay linear dynamic range and lower limit of detection(LLOD)were also assessed.Results:The assay could detect the presence of HIV-1 copies 100%at concentrations of 6.3 copies/reaction,and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction(95%confidence intervals[CI]:3.6-6.5 copies/reaction)with linearity over a 5-log_(10)-unit range in total HIV DNA assay.For the integrated HIV DNA assay,the LLOD was 8.0 copies/reaction(95%CI:5.8-16.6 copies/reaction)with linearity over a 3-log 10-unit range.Total HIV DNA in CD4^(+)T cells was positively associated with integrated HIV DNA(r=0.76,P<0.0001).Meanwhile,both total HIV DNA and integrated HIV DNA in CD4^(+)T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8^(+)T-cell counts.Conclusions:This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity.It can be readily adapted for measuring HIV DNA with non-B clades,and it could be beneficial for testing in clinical trials.

关键词： Human immunodeficiency virus HIV Integrated HIV-1 DNA Total HIV DNA Droplet digital polymerase chain reaction HIV reservoir Antiretroviral therapy

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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 pathogenesis.Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis.Accumulating evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of ACLF.Lon protease-1(LONP1)is a novel mediator of energy and glucose metabolism.However,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods: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 model.LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation.Liver 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 ACLF.Results:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues.Furthermore,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 mice.Moreover,mitochondrial morphology was improved upon overexpression of LONP1.Meanwhile,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression.Similarly,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 disorders.Conclusion:We demonstrated that gluconeogenesis dysfunc

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

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Intestinal microecological transplantation for a patient with chronic radiation enteritis:A case report

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World Journal of Gastroenterology 2024年第19期30卷 2603-2611页

作者： Lin Wang Yan Li Yu-Jing Zhang Li-Hua Peng Department of Gastroenterology and hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Gastroenterology and hepatology Chinese PLA Medical SchoolBeijing 100853China

BACKGROUND The gut microbiota is strongly associated with radiation-induced gut damage.This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.CASE SUMMARY A 64-year-old female with cervical cancer developed abdominal pain,diarrhea,and blood in the stool 1 year after radiotherapy.An electronic colonoscopy was performed to diagnose chronic radiation enteritis.Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed.The patient experienced short-and long-term relief from symptoms without adverse effects.Whole 16S rRNA sequencing revealed significant differences in the intestinal flora’s composition between patient and healthy donors.Pathogenic bacteria,such as Escherichia fergusonii and Romboutsia timonensis,were more in the patient.Beneficial bacteria such as Faecalibacterium prausnitzii,Fusicatenibacter saccharivorans,Ruminococcus bromii,and Bifidobacterium longum were more in the healthy donors.Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition.The composition converged with the donor's flora,with an increase in core beneficial intestinal bacteria,such as Eubacterium rectale,and a decrease in pathogenic bacteria.Changes in the intestinal flora corresponded with the patients'alleviating clinical symptoms.CONCLUSION Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora.This study provides a new approach for treating patients with chronic radiation enteritis.

关键词： Chronic radiation enteritis Gut microbial transplantation Intestinal microecology Cancer Quality of life Case report

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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 criteria.Sarcopenia has recently been recognized as a new prognostic factor for predicting outcomes in LT candidates.AIM To estimate the prevalence of sarcopenia and evaluate its clinical effect on LT candidates.METHODS 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 30,2022.Cohort studies of the definition of sarcopenia that estimate sarcopenia prevalence and evaluate its effect on clinical outcomes and the risk of mortality were included.RESULTS Twenty-five studies involving 7760 patients undergoing LT were included.The 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.CONCLUSION 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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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

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Biomedical and Environmental Sciences 2024年第5期37卷 494-502页

作者： CAO Wei Hua JIANG Ting Ting SHEN Ge DENG Wen WANG Shi Yu ZHANG Zi Yu LI Xin Xin LU Yao ZHANG Lu LIU Ru Yu CHANG Min WU Shu Ling GAO Yuan Jiao HAO Hong Xiao CHEN Xiao Xue HU Lei Ping XU Meng Jiao YI Wei XIE Yao LI Ming Hui Department of hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China Department of Gynecology and Obstetrics Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

关键词： Drug-induced liver injury Cytokines Non-steroidal anti-inflammatory drugs Inflammation

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Comparison of tailpipe carbonyls and volatile organic compounds emissions from in-use gasoline/CNG bi-fuel vehicles

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Journal of Environmental Sciences 2024年第1期135卷 619-629页

作者： Jiachen Li Yunshan Ge Xin Wang Mengzhu Zhang Haohao Wang School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100081China

Ground-level ozone contamination has been globally an urban air quality issue,particularly for China,which has recently made significant progress in purifying its sky.Unregulated exhaust emissions from motor vehicles,predominantly carbonyls and volatile organic compounds(VOCs),are among the leading contributors to ozone formation.In this chassislevel study,the unregulated emissions from five China-5 certified gasoline/CNG bi-fuel taxis,along with their ozone forming potential(OFP),were evaluated.It is found that carbonyls and VOCs were mainly emitted during the starting phase no matter the engine was cold or hot.Compared to gasoline,CNG fueling reduced VOCs emissions on a large scale,especially in the starting phase,but had elevated carbonyls.On a fleet average,CNG fueling derived 15%and 46%less OFP than gasoline in cold-and hot-start tests,respectively.VOCs contributed to over 90%of the total OFP of the exhaust.In terms of alleviating ground-level ozone contamination,CNG is a feasible alternative to gasoline on light-duty vehicles.

关键词： CNG Gasoline Carbonyls VOCs OFP

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Compositional evolution for mixed aerosols containing gluconic acid and typical nitrate and the effect of multiply factors on hygroscopicity

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Journal of Environmental Sciences 2024年第5期139卷 206-216页

作者： Yue Zhu Shufeng Pang Yunhong Zhang School of Chemistry and Chemical Engineering Beijing Institute of TechnologyBeijing 100081China

The aging process of atmospheric aerosols usually leads to a mixture of inorganic salts and organic compounds of anthropogenic origin.In organic compounds,polyhydroxy organic acids are important components,however,the study on composition and hygroscopic properties of the mixture containing inorganics and polyhydroxy organic acids is scanty.In this study,gluconic acid,the proxy of polyhydroxy organic acids,is mixed with the representative nitrate(Mg(NO_(3))_(2),Ca(NO_(3))_(2))to form aerosols.ATR-FTIR and optical microscopy are employed to study the component changes and hygroscopicity as a function of relative humidity.As relative humidity fluctuates,the FTIR-ATR spectra display that the internal mixed gluconic acid(CH_(2)(CH)_(4)(OH)_(5)COOH)and nitrate can react to release acidic gases,forming relevant gluconate and further affecting the hygroscopicity.The specific presentation is particles cannot be recovered to their original size after the dehydration-hydration process and there will be some disparities in GF for mixed particles.For the gluconic acid-Ca(NO_(3))_(2)/Mg(NO_(3))_(2)mixtures with molar ratios of 1:1,higher degree of reaction resulting in the production of large amounts of gluconate should be responsible to the lower hygroscopicity compared to ZSR model.For 1:2 gluconic acid-nitrate mixed systems(with higher nitrate content),the hygroscopicity of mixtures are higher than the ZSR prediction.A possible reason could be‘salt-promoting effect’on the organic fractions of the surplus inorganic salt in the mixture.These data can improve the chemical composition list evaluation,in turn hygroscopic properties and phase state of atmospheric aerosol,and then the climate effect.

关键词： Hygroscopicity Gluconic acid Reaction ZSR simulation Size growth factors

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