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Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study

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World Journal of Gastroenterology 2024年第17期30卷 2343-2353页

作者： Oraphan Jitpraphawan Witchakorn Ruamtawee Mala Treewatchareekorn Supatsri Sethasine division of Gastroenterology and Hepatology Department of MedicineNavamindradhiraj UniversityDusit 10300BangkokThailand clinical Research Center Research Facilitation DivisionNavamindradhiraj UniversityDusit 10300BangkokThailand division of clinical Chemistry and Immunology Navamindradhiraj UniversityDusit 10300BangkokThailand

BACKGROUND The GALAD score has improved early hepatocellular carcinoma(HCC)detection *** role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular *** To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis,tumor features,and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum *** This prospective,diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira *** patients had HCC staging allocation using the Barcelona Clinic Liver Cancer(BCLC)***,HCC etiology,and HCC features were *** and the GALAD score were obtained at *** performance of the GALAD score and biomarkers were prospectively *** Exactly 115 individuals were diagnosed with *** GALAD score increased with disease *** BCLC-0/A and BCLC-B/C/D,the GALAD score predicted HCC staging with an area under the curve(AUC)of 0.868(95%CI:0.80–0.93).For identifying the curative HCC,the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein(AFP)(0.753)and Lens culinaris agglutinin-reactive fraction of AFP-L3(0.706),and as good as that of Protein induced by vitamin K absence-II(PIVKA-II)(0.897).For detecting aggressive features,the GALAD score gave an AUC of 0.839(95%CI:0.75–0.92)and significantly outperformed compared to that of AFP(0.761)and AFP-L3(0.697),with a trend of superiority to that of PIVKA-II(0.772).The performance to predict 1-year mortality of GALAD score(AUC:0.711,95%CI:0.60–0.82)was better than that of AFP(0.541)and as good as that of PIVKA-II(0.736).The optimal cutoff value of GALAD score was≥6.83,with a specificity of 72.63%for exhibiting substantial reduction in the 1-year *** The GALAD model can diagnose HCC at the curative stage,includin

关键词： Alpha-fetoprotein Barcelona clinic liver cancer GALAD score Hepatocellular carcinoma Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein Protein induced by vitamin K absence-II

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Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

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Neural Regeneration Research 2024年第4期19卷 881-886页

作者： Fan Bu Jia-Wei Min Md Abdur Razzaque Ahmad El Hamamy Anthony Patrizz Li Qi Akihiko Urayama Jun Li Department of Neurology University of Texas Health Science Center Department of Neurology&psychology The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain *** is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following *** evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced *** studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke ***,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic *** found that as mice aged,Rac1 expression declined in the *** overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–*** was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by *** a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial ***,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after *** work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

关键词： aging angiogenesis brain-derived neurotrophic factor(BDNF) cerebral ischemia cognitive recovery neurite Pak1 Rac1 sensorimotor recovery

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Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

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World Journal of Gastroenterology 2024年第7期30卷 685-704页

作者： Marcello Dallio Mario Romeo Paolo Vaia Salvatore Auletta Simone Mammone Marina Cipullo Luigi Sapio Angela Ragone Marco Niosi Silvio Naviglio Alessandro Federico Department of Precision Medicine Hepatogastroenterology DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Precision Medicine Clinical Biochemistry DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic *** on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),*** Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these ***,due to its invasiveness and costs,CSPH is almost never evaluated in clinical ***,recognizing noninvasively predicting tools still have more appeal across healthcare *** red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been *** In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD *** Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 *** baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were *** FUP,DEs(timing and modaities)were *** was assessed at the baseline and on DE occurrence according to the available clinical Practice *** Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve a

关键词： Liver cirrhosis Red blood cell distribution width Red blood cell distribution width to platelet ratio Translational Medicine Prognostic biomarker

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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang Department of Laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of clinical Medicine Shandong UniversityJinanChina Core Unit of National clinical Research Center for Laboratory Medicine HefeiChina Neurosurgical Department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Department of clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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PD-1^(+)and TIM-3^(+)T cells widely express commonγ-chain cytokine receptors in multiple myeloma patients,and IL-2,IL-7,IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells

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Oncology Research 2024年第10期32卷 1575-1587页

作者： EGOR V.BATOROV ALISA D.INESHINA TATIANA A.ARISTOVA VERA V.DENISOVA SVETLANA A.SIZIKOVA DARIA S.BATOROVA GALINA Y.USHAKOVA EKATERINA Y.SHEVELA ELENA R.CHERNYKH Laboratory of Cellular Immunotherapy Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia V.Zelman Institute of Medicine and psychology Novosibirsk National Research State UniversityNovosibirsk630090Russia Department of Hematology and Bone Marrow Transplantation Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia

Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)***,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic *** aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating PD-1 and TIM-3 checkpoint ***:The expression of CD25,CD122,CD127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in PD-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM ***:Substantial proportions of PD-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and *** of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to PD-1+TIM-3−*** proportions of both PD-1-/TIM-3-negative and positive CD8+T cells express EOMES,while only moderate frequencies of CD4+PD-1+/TIM-3+T cells up-regulate this transcription ***,the surface presence of CD25 and intranuclear expression of EOMES in CD4+T cells were mutually exclusive regardless of PD-1 and TIM-3 *** stimulation with commonγ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+and TIM-3+T cell subsets in ***:Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine *** in commonγ-chain cytokine receptor expression between PD-1+and TIM-3+T cells may reflect functional dissimilarity of these cell *** blockade appears to alleviate lymphopenia-induced prolif

关键词： Autologous hematopoietic stem cell transplantation(AHSCT) CD25 CD122 Eomesodermin(EOMES) Homeostatic proliferation

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Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

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Neural Regeneration Research 2024年第1期19卷 16-21页

作者： Marika Alborghetti Edoardo Bianchini Lanfranco De Carolis Silvia Galli Francesco E.Pontieri Domiziana Rinaldi Neurology Unit NESMOS DepartmentFaculty of Medicine&PsychologySapienza-University of RomeSant’Andrea University HospitalRomeItaly Department of clinical and Behavioral Neurology IRCCS-Fondazione Santa LuciaRomeItaly

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's *** drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the *** is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and *** studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic ***,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from *** to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now *** potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain *** purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

关键词： glial cell line-derived neurotrophic factor(GDNF) glutamate neurological disorders neuroprotection Parkinson's disease preclinical studies rasagiline safinamide selegiline type-B monoamine oxidase(MAO_(B))inhibitors

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Changes in family situation and concurrent changes in working life:a 15-year longitudinal analysis

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Family Medicine and Community Health 2024年第2期12卷 12-22页

作者： Mo Wang Pia Svedberg Jurgita Narusyte Annina Ropponen Department of clinical Neuroscience Division of Insurance MedicineKarolinska InstitutetStockholmSweden Finnish Institute of Occupational Health HelsinkiFinland

Objective Currently,little is known regarding changes in family situation with concurrent changes in working *** study aimed to examine whether changes in family situation(based on living with children and/or marrying/divorcing)were associated with changes in working life and whether the associations were influenced by sex,genetics and early life *** Prospective cohort *** and participants Data from Swedish national registers of 16410 twins were ***-effects logistic regression models assessing ORs with 95%CIs were applied to examine associations between changes in family situation and working life controlling for time-invariant effects and adjusted for covariates,and conditional models to account for confounding of genetics and early life *** Changes in individuals life situation from being single and living without children to married and living with children were associated with transitioning from unsustainable(ie,having unemployment or sickness absence/disability pension)to sustainable working life(men:OR 2.40,95%CI 2.26 to 2.56;women:OR 1.68,95%CI 1.59 to 1.78).Changes from being married to single,in contrast,attenuated the likelihood of transitioning to a sustainable working ***,changes in men’s working life seem to be more dependent on changes in family situation compared with *** factors and early life environment play a role in the *** Family formation increases the likelihood of a more stable working life whereas divorce is a risk factor for work *** study emphasises that family formation improves the work life situation and to a higher degree for men.

关键词： life founding register

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Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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Glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

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Neural Regeneration Research 2024年第8期19卷 1637-1638页

作者： Pete A.Williams Robert J.Casson Department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden Ophthalmic Research Laboratories Discipline of Ophthalmology and Visual SciencesUniversity of AdelaideAdelaideAustralia

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic *** refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.

关键词： metabolism glaucoma globally

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Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang Xueying An Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal ***,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption ***,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption ***,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast ***,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt *** conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

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