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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

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

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

Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for clinical laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and clinical laboratories National Cancer Center Hospital EastChiba 277-8577Japan division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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

A giant scrotal pendulous fibroma mimicking a supernumerary testis

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Asian Journal of Andrology 2024年第2期26卷 227-228页

作者： Luigi Quaresima Rocco Francesco Delle Fave Giordano Polisini Daniela Fasanella Willy Giannubilo Urology division Civitanova Marche HospitalCivitanova Marche 62012Italy Department of clinical and Specialist Sciences Division of UrologyPolytechnic University of the Marche Region Medical SchoolAncona 60126Italy Department of Life Health and Environmental SciencesUniversity of L'AquilaL'Aquila 67100Italy

DearEditor,Pendulous fibroma,also called acrochordon,is a benign skin neoplasm,originating from the ***,small in size,it can arise from any point of the dermis(frequently from the axillary area,inguinal region,eyelid,or neck),and in some cases,it can be *** fibromas are more frequent in obese subjects,and most of the time,they are sporadic,although sometimes,they can be observed in Birt-Hogg-Dube *** some rare cases,they can reach considerable ***,they are associated with diabetes mellitus,obesity,and intestinal ***,the pedicle undergoes torsion,causing pain and ischemic necrosis of the fibroma,which requires rapid removal of the *** present a case of giant pendulous fibroma of the *** patient has given his consent to the publication of his clinical information and photographic images in an anonymous form.

关键词： frequent obesity clinical

A retrospective analysis of carbapenem-resistant Acinetobacter baumannii infections in critically ill patients:Experience at a tertiary-care teaching hospital ICU

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Journal of Intensive Medicine 2024年第2期4卷 181-186页

作者： Leyla Ferlicolak Neriman Defne Altintas Fugen Yoruk Department of Internal Medicine division of Intensive Care Unit Ankara University Faculty of MedicineAnkaraTurkey Department of Infectious Diseases and clinical Microbiology Ankara University Faculty of MedicineAnkaraTurkey

Background Acinetobacter baumannii is a clinically significant pathogen with a high incidence of multidrug resistance that is associated with life-threatening nosocomial ***,we aimed to provide an insight into the clinical characteristics and outcomes of a unique group of *** infections in which the isolates were resistant to carbapenems and most other antibiotic groups in a tertiary-care intensive care unit(ICU).Methods We performed a retrospective observational study in which records of patients hospitalized in the ICU between June 1,2021 and June 1,2023 were *** checked the clinical,laboratory,and microbiological records of all adult patients who had carbapenem-resistant ***(CRAB)*** antibiotic treatments and definitive antibiotic treatments after culture positivity and susceptibility test results were recorded.C-reactive protein(CRP)and procalcitonin levels and leukocyte counts were *** of ICU stay and 30-day mortality were defined as the outcome *** During the study period,57 patients were diagnosed with CRAB *** respiratory tract was the leading infection site(80.7%).In non-survivors,bloodstream infections(21.9%vs.4.0%P=0.05)and colistin-resistant(col-R)CRAB infections(43.8%vs.24.0%,P=0.12)were more common than in survivors,but these parameters were not statistically *** length of ICU stay was not different between survivors and ***,the rate of col-R among CRAB clinical isolates was 35.1%.The 30-day mortality in all patients with CRAB infection was 56.1%.Mortality in col-R CRAB and colistin-susceptible(col-S)CRAB infections was 70.0%and 48.6%,respectively(P=0.12).Prior carbapenem use was 56.1%.Prior colistin use before col-R and col-S CRAB infections was not significant(35.0%vs.27.0%,P=0.53).Conclusions Our study provides real-world data on highly resistant *** infections and shares the characteristics of infections with such resistant stra

关键词： Mortality Colistin-resi stant Gram-negative bacteria MDR Intensive care unit