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Salivary metabolites are promising noninvasive biomarkers of druginduced liver injury

World Journal of Gastroenterology 2024年第18期30卷 2454-2466页

作者： Si-Miao Yu Hao-Cheng Zheng Si-Ci Wang wen-ya rong Ping Li Jing Jing Ting-Ting He Jia-Hui Li XiaDing Rui-Lin Wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Hepatology of Traditional Chinese Medicine The Fifth Medical Center of PLA General HospitalBeijing 100039China The First Clinical Medical College Henan University of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina

BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.

关键词： Drug-Induced liver injury Salivary Metabolomics Biomarker Weighted metabolite Coexpression network analysis Machine learning Noninvasive Diagnostic method Metabolites

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Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 299-310页

作者： LIU Xiao-rong LI Shuo-fu MEI wen-ya LIU Xiang-dan ZHOU Ri-bao College of Pharmacy Hunan University of Chinese MedicineChangsha(410208)China Department of Orthopaedics The First Hospital of Hunan University of Chinese MedicineChangsha(410007)China

Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10,20 and 40µmol/L).Overexpression vectors for matrix metalloproteinase-2(MMP2)or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function.RA-FLS viability,migration,and invasion were evaluated.Moreover,a collagen-induced arthritis(CIA)rat model was established.Rats were randomly divided to sham,CIA,low-,medium-,and high-dosage groups using a random number table(n=5 in each group)and administed with normal saline or additional isorhamnetin[2,10,and 20 mg/(kg·day)]for 4 weeks,respectively.Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats.The levels of MMP2,MMP9,TNF-α,interleukin-6(IL-6),and IL-1β,as well as the phosphorylation levels of SRC,extracellular regulated kinase(ERK),and cyclic adenosine monophosphate response element-binding(CREB),were detected in RA-FLS and synovial tissue.Molecular docking was also used to analyze the binding of isorhamnetin to SRC.Results In in vitro studies,isorhamnetin inhibited RA-FLS viability,migration and invasion(P<0.05).Isorhamnetin downregulated the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1βin RA-FLS(P<0.05).The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion,as well as the levels of TNF-α,IL-6,and IL-1β(P<0.05).Furthermore,isorhamnetin bound to SRC and reduced the phosphorylation of SRC,ERK,and CREB(P<0.05).SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability,migration and invasion,as well as the negative regulation of MMP2 and MMP9(P<0.05).In in vivo studies,isorhamnetin decreased arthritis index scores(P<0.05)and alleviated synovial inflammation.Isorhamnetin reduced the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1β,as well as the phosphorylation of SRC,ERK,and CREB in synovial tissue(P<0.05).Notably,the inhibit

关键词： rheumatoid arthritis isorhamnetin SRC/ERK/CREB matrix metalloproteinase

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Clinical value of precise rehabilitation nursing in management of cerebral infarction

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World Journal of Clinical Cases 2024年第1期12卷 24-31页

作者： ya-Na Xu Xiu-Zhen Wang Xiao-rong Zhang Department of Neurology Wuhan Fourth HospitalWuhan 430030Hubei ProvinceChina Department of Neurosurgery The First People's Hospital of Jiangxia DistrictWuhan City(Union Jiangnan Hospital of Huazhong University of Science and Technology)Wuhan 430200Hubei ProvinceChina

BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,ischemia,and hypoxia.The precision rehabilitation nursing model for chronic disease management is a continuous,fixed,orderly,and efficient nursing model aimed at standardizing the clinical nursing process,reducing the wastage of medical resources,and improving the quality of medical services.AIM To analyze the value of a precise rehabilitation nursing model for chronic disease management in patients with cerebral infarction.METHODS Patients(n=124)admitted to our hospital with cerebral infarction between November 2019 and November 2021 were enrolled as the study subjects.The random number table method was used to divide them into a conventional nursing intervention group(n=61)and a model nursing intervention group(n=63).Changes in the nursing index for the two groups were compared after conventional nursing intervention and precise rehabilitation intervention nursing for chronic disease management.RESULTS Compared with the conventional intervention group,the model intervention group had a shorter time to clinical symptom relief(P<0.05),lower Hamilton Anxiety Scale and Hamilton Depression Scale scores,a lower incidence of total complications(P<0.05),a higher disease knowledge mastery rate,higher safety and quality,and a higher overall nursing satisfaction rate(P<0.05).CONCLUSION The precision rehabilitation nursing model for chronic disease management improves the clinical symptoms of patients with cerebral infarction,reducing the incidence of total complications and improving the clinical outcome of patients,and is worthy of application in clinical practice.

关键词： Precise rehabilitation nursing model for chronic disease management Cerebral infarction Knowledge of disease Safety and quality

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Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

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Chinese Journal of Integrative Medicine 2024年第6期30卷 559-564页

作者： ZHANG rong-rong SHAO Ming-yi FU Yu ZHAO Rui-xia WANG Jing-wen FANG Yu-xuan The First Clinical Medical College of Henan University of Traditional Chinese Medicine Zhengzhou450046China Personal Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Scientific Research Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Digestive Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical decision-making.MethodsRandomized controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation results.ResultsA total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, respectively.ConclusionBased on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

关键词： multi-criteria decision analysis benefit-risk assessment Chinese medicine injections primary livercancer

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Impact of Carbon Chain Structures in the Backbone on the Flexibility of Modified Polyarylene Sulfide Resins: Molecular Dynamics Simulations and Mesoscopic Analysis

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Chinese Journal of Polymer Science 2024年第4期42卷 544-557页

作者： Chi Zhang rong Liu Jing-Yuan Liu wen-Wei Jiang Key Laboratory of Fine Chemical Engineering and Functional Materials School of Chemical EngineeringSichuan UniversityChengdu610065China

In the domain of high-performance engineering polymers, the enhancement of mechanical flexibility in poly(phenylene sulfide) (PPS) resins has long posed a significant challenge. A novel molecular structure, designated as PP-He-IS, wherein imide rings and an aliphatic hexylene chain are covalently incorporated into the PPS backbone to enhance its flexibility, is introduced in this study. Molecular dynamics (MD) simulations are employed to systematically explore the effects of diversifying the backbone chain structures by substituting phenyl units with alkyl chains of varying lengths, referred to as PP-A-IS where “A” signifies the distinct intermediary alkyl chain configurations. Computational analyses reveal a discernable decrement in the glass transition temperature (Tg) and elastic modulus, counterbalanced by an increment in yield strength as the alkyl chain length is extended. Notably, the PP-He-IS variant is shown to exhibit superior yield strength while simultaneously maintaining reduced elastic modulus and Tg values, positioning it as an advantageous candidate for flexible PPS applications. Mesoscopic analyses further indicate that structures such as PP-He-IS, PP-Pe-IS, and PP-Bu-IS manifest remarkable flexibility, attributable to the presence of freely rotatable carbon-carbon single bonds. Experimental validation confirms that a melting temperature of 504 K which is lower than that of conventional PPS, and lower crystallinity are exhibited by PP-He-IS, thereby affording enhanced processability without compromising inherent thermal stability. Novel insights into the strategic modification of PPS for mechanical flexibility are thus furnished by this study, which also accentuates the pivotal role played by molecular dynamics simulations in spearheading high-throughput investigations in polymer material modifications.

关键词： Molecular dynamics simulations Polyarylene Sulfide Main-chain modifications Flexibility Aliphatic hexylene chain

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N-glycan biosignatures as a potential diagnostic biomarker for earlystage pancreatic cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 659-669页

作者： yan-rong wen Xia-wen Lin Yu-wen Zhou Lei Xu Jun-Li Zhang Cui-Ying Chen Jian He Department of Nuclear Medicine Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of Research and Development Sysdiagno(Nanjing)Biotech Co.LtdNanjing 210008Jiangsu ProvinceChina

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)has a poor prognosis,with a 5-year survival rate of less than 10%,owing to its late-stage diagnosis.Early detection of pancreatic cancer(PC)can significantly increase survival rates.AIM To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis.METHODS An extensive patient cohort was used to determine a biomarker signature,in-cluding patients with PDAC that was well-defined at an early stage(stages I and II).The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I,22 with stage II,4 with stage III,16 with stage IV PDAC,and 88 controls.We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan sig-nature-based diagnosis model called the“Glyco-model”.RESULTS The biomarker signature was created to discriminate samples derived from patients with PC from those of controls,with a receiver operating characteristic area under the curve of 0.86.In addition,the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls,with a receiver operating characteristic area under the curve of 0.919.Glyco-model demonstrated favorable diagnostic performance in all stages of PC.The diagnostic sensitivity for stage I PDAC was 89.66%.Core Tip:This study employed a patient cohort to investigate the N-glycan signature of early-stage pancreatic cancer(PC).Serum N-glycans analysis was conducted to identify the serum biomarker signature associated with early-stage pancreatic ductal adenocarcinoma(PDAC),resulting in the identification of nine early-stage PDAC N-glycan signatures.Subsequently,utilizing these biosignatures,a diagnostic model named the“Glyco-model”was developed,demonstrating promising diagnostic performance across all stages of PC.The study revealed that the diagnostic sensitivity for stage I PDAC was determined to be 89.66%.Consequently,this diagnostic model exhibits potent

关键词： Glycomics N-glycans Biomarkers Pancreatic cancer Predictive modeling

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Morphology Study for GeV Emission of Nearby Supernova Remnant G332.5-5.6

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Research in Astronomy and Astrophysics 2024年第4期24卷 134-140页

作者： Ming-Hong Luo Qing-wen Tang Xiu-rong Mo Department of Physics School of Physics and Materials ScienceNanchang UniversityNanchang 330031China

A spatial template is important to study nearby supernova remnants(SNRs).For SNR G332.5-5.6,we report a Gaussian disk with a radius of about 1°.06 to be a potential good spatial model in the γ-ray band.Employing this new Gaussian disk,its GeV lightcurve shows a significant variability of about seven sigma.The γ-ray observations of this SNR could be explained well either by a leptonic model or a hadronic model,in which a flat spectrum for the ejected electrons/protons is required.

关键词： ISM:supernova remnants gamma rays:ISM

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Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

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Chinese Journal of Integrative Medicine 2024年第4期30卷 348-358页

作者： FU Yu-bing LIU Chen-feng WANG Jin-jia JI Xiao-lin TANG rong-han LIAO Kun-yu CHEN Ling-yue HONG ya-zhen FAN Bin-bin WANG Shi-cong LIU wen-Hsien State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life ScienceXiamen UniversityXiamenFujian Province(361102)China Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development ZhangzhouFujian Province(363000)China

Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

关键词： Pien Tze Huang metastasis anti-tumor immunity T cell activation T cell exhaustion immune checkpoints Chinese medicine

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High-precision parallel computing model of solute transport based on GPU acceleration

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Journal of Hydrodynamics 2024年第1期36卷 202-212页

作者： Shang-hong Zhang rong-qi Zhang wen-da Li Xi-yan yang yang Zhou School of Water Resources and Hydropower Engineering North China Electric Power UniversityBeijing102206China Hubei Key Laboratory of Intelligent yangtze and Hydroelectric Science China Yangtze Power Co.Ltd.Yichang443133China

The scenario simulation analysis of water environmental emergencies is very important for risk prevention and control,and emergency response.To quickly and accurately simulate the transport and diffusion process of high-intensity pollutants during sudden environmental water pollution events,in this study,a high-precision pollution transport and diffusion model for unstructured grids based on Compute Unified Device Architecture(CUDA)is proposed.The finite volume method of a total variation diminishing limiter with the Kong proposed r-factor is used to reduce numerical diffusion and oscillation errors in the simulation of pollutants under sharp concentration conditions,and graphics processing unit acceleration technology is used to improve computational efficiency.The advection diffusion process of the model is verified numerically using two benchmark cases,and the efficiency of the model is evaluated using an engineering example.The results demonstrate that the model perform well in the simulation of material transport in the presence of sharp concentration.Additionally,it has high computational efficiency.The acceleration ratio is 46 times the single-thread acceleration effect of the original model.The efficiency of the accelerated model meet the requirements of an engineering application,and the rapid early warning and assessment of water pollution accidents is achieved.

关键词： Pollution transport and diffusion model parallel computing Compute Unified Device Architecture(CUDA) pollution event

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Pt nanoclusters modified porous g-C_(3)N_(4)nanosheets to significantly enhance hydrogen production by photocatalytic water reforming of methanol

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Chinese Journal of Chemical Engineering 2024年第2期66卷 40-50页

作者： Yi-Fei Liang Jin-rong Lu Shang-Kun Tian wen-Quan Cui Li Liu Hebei Provincial Key Laboratory of Environmental Photocatalytic and Electrocatalytic Materials College of Chemical EngineeringNorth China University of Science and TechnologyTangshan 063210China

For the use of green hydrogen energy,it is crucial to have efficient photocatalytic activity for hydrogen generation by water reforming of methanol under mild conditions.Much attention has been paid to gC_(3)N_(4)as a promising photocatalyst for the generation of hydrogen.To improve the separation of photogenerated charge,porous nanosheet g-C_(3)N_(4)was modified with Pt nanoclusters(Pt/g-C_(3)N_(4))through impregnation and following photo-induced reduction.This catalyst showed excellent photocatalytic activity of water reforming of methanol fo r hydrogen production with a 17.12 mmol·g^(-1)·h^(-1)rate at room temperature,which was 311 times higher than that of the unmodified g-C_(3)N_(4).The strong interactions of Pt-N in Pt/g-C_(3)N_(4)constructed effective electron transfer channels to promote the separation of photogenerated electrons and holes effectively.In addition,in-situ infrared spectroscopy was used to investigate the intermediates of the hydrogen production reaction,which proved that methanol and water eventually turn into H_(2)and CO_(2)via formaldehyde and formate.This study provides insights for understanding the photocatalytic hydrogen production in the water reforming of methanol.

关键词： Water reforming of methanol Photocatalysis g-C_(3)N_(4) Pt nanoclusters Hydrogen production

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