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Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease via necroptosis-independent pathway

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World Journal of Gastroenterology 2025年第6期31卷 44-61页

作者： Han-Ning Xuan yuan Hyun Sung Kim Gye Ryeol Park Jae Eun Ryu Ji Eun Kim In young Kang Hye young Kim Seung Min Lee Ju Hee Oh Eileen L yoon Dae Won Jun department of internal medicine Hanyang University School of MedicineSeoul 04763South Korea department of Pathology Hanyang University School of MedicineSeoul 04763South Korea department of Translational medicine Graduate School of Biomedical Science and EngineeringHanyang UniversitySeoul 04763South Korea department of Obstetrics and Gynecology Institute of Women’s Medical Life ScienceYonsei Cancer CenterSeverance HospitalYonsei University College of MedicineSeoul 04763South Korea department of internal medicine Sanggye Paik HospitalInje University College of MedicineSeoul 01757South Korea

BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver *** study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease *** focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related *** To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver *** Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various *** human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate ***,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver *** While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and ***,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid *** MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease *** MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

关键词： RAW 264.7 cell Cell death Necroptosis Mixed lineage kinase domain-like protein Non-alcoholic fatty liver disease Mixed lineage kinase domain-like protein adenosine triphosphate binding inhibitor Alcoholic liver disease

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Assessment of new pathological markers in early stage colon cancer:Insights and limitations

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World Journal of Gastrointestinal Oncology 2025年第3期17卷 113-121页

作者： Bulent Erdogan Fatma Elif UsturalıKeskin ErkanÖzcan Ahmet Küçükarda Ali Kaan Güren Osman Köstek Bekir Muhammet Hacioglu Hilmi Kodaz department of Medical Oncology Division of Medical OncologyDepartment of Internal MedicineTrakya University School of MedicineEdirne 22000Türkiye department of Pathology Trakya University School of MedicineTrakya UniversityEdirne 22000Türkiye Division of Medical Oncology Trakya University School of MedicineEdirne 22000Türkiye Division of Medical Oncology Department of Internal MedicineTrakya University School of MedicineEdirne 22000Türkiye Division of Medical Oncology Department of Internal MedicineMarmara University School of MedicineMarmara UniversityIstanbul 34000Türkiye Division of Medical Oncology Department of Internal MedicineMarmara University School of MedicineIstanbul 34000Türkiye department of Medical Oncology Acibadem Eskisehir HospitalEskisehir 26130Türkiye

BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or ***-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being *** To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,department of Medical *** divided those with and without high-risk factors into two *** examined the relationship of new pathological markers with these groups and with pathological markers in risk *** There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T *** No relationship was found between the presence of new pathological markers and high-low risk *** we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.

关键词： Colon cancer Early stage Risk factors New pathological markers Tumor-stroma ratio Tumor infiltrating lymphocytes Crohn-like reaction Desmoid reaction Poorly differentiated clusters

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Predictive value of the systemic immune inflammation index in recurrence of atrial fibrillation after radiofrequency catheter ablation

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World Journal of Cardiology 2025年第1期17卷 22-27页

作者： Alexander E Berezin department of internal medicine-II Paracelsus Medical University SalzburgSalzburg 5020Austria

The recurrence of atrial fibrillation(AF)in patients after successful radiofrequency catheter ablation(RFCA)appears to be an unresolved clinical issue and needs to be clearly *** are many factors associated with AF recurrence,such as duration of AF,male sex,concomitant heart failure,hemodynamic parameters,chronic obstructive pulmonary disease,hypertension,obstructive sleep apnea,hyperthyroidism,smoking and ***,the inflammatory changes are strongly associated with electrical and structural cardiac remodeling,cardiac damage,myocardial fibrotic changes,microvascular dysfunction and altered reparative *** this context,biomarkers reflecting the different stages of AF pathogenesis deserve thorough *** authors of the retrospective study revealed that one-year recurrence rate of non-valvular AF in the high systemic immune inflammation(SII)index group was significantly increased compared to that of the low SII index group and provided additional predictive value to the ***,the authors suggest that this biomarker may help physicians to optimize the selection of AF patients and to develop a personalized treatment *** conclusion,the SII index may serve as a valuable indicator of recurrent AF in patients after RFCA and may be a biomarker with plausible predictive value for poor clinical outcomes.

关键词： Systemic immune inflammation index Recurrent atrial fibrillation Radiofrequency catheter ablation Biomarkers APPLE score Prediction

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Efficacy and Safety of Zihua Wenfei Zhisou Granule in Treatment of Postinfectious Cough: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase Ⅱ Clinical Trial

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Chinese Journal of Integrative medicine 2025年第1期31卷 3-10页

作者： LI Ting LIU Xue-mei yANG Mei WU yan-qing LIU Wei MAO Bing JIANG Hong-li Division of Pulmonary medicine Department of Internal MedicineInstitute of Integrated Traditional Chinese and Western MedicineWest China HospitalSichuan UniversityChengdu610041China department of Pulmonary Diseases State Key Laboratory of Biotherapy of ChinaWest China HospitalSichuan UniversityChengdu610041China

Objective: To evaluate the efficacy and safety of Chinese medicine(CM) Zihua Wenfei Zhisou Granule(ZWZG) in postinfectious cough(PIC) patients with CM syndrome of wind-cold invading Fei(Lung,WCIF). Methods: This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase Ⅱclinical trial. PIC patients with WCIF syndrome were recruited from the Respiratory departments in 6 hospitals across China between March 2019 and December 2020. Eligible patients were randomly assigned to group A(ZWZG-matched placebo 15 g), group B(active ZWZG 15 g), and group C(active ZWZG 10 g plus ZWZGmatched placebo 5 g) in a 1:1:1 ratio. All medications were taken orally 3 times daily for 14 consecutive days. The primary outcomes were cough relief rate and cough disappearance rate. The secondary outcomes included time to cough relief, time to cough disappearance, and changes in cough symptom score(CSS), cough Visual Analog Scale(VAS) value, Cough-Specific Quality of Life Questionnaire(CQLQ) score, and CM syndrome score from baseline(day 0) to post-treatment(day 14). Adverse events(AEs) in each group were recorded. Results: A total of 198 patients were included in the full analysis set(FAS) and safety analysis set(SS), while 183 were enrolled in the per-protocol analysis set(PPS). In the FAS population, the cough relief rate was 47.76%, 90.77% and 84.85%in groups A, B, and C, respectively;while the cough disappearance rate was 31.34%, 72.31% and 68.18%,respectively. The cough relief rates and cough disappearance rates in groups B and C were significantly higher than group A(Py greater improvements from baseline to post-treatment in CSS during daytime and nighttime as well as VAS(Pyndrome

关键词： postinfectious cough Zihua Wenfei Zhisou Granule randomized controlled trial Chinese medicine

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Patients admitted in the intensive care unit after solid organ or bone marrow transplantation:Retrospective cohort study

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World Journal of Transplantation 2025年第1期15卷 95-104页

作者： Ana Vujaklija Brajkovic Iva Kosuta Lucija Batur Sara Sundalic Marijana Medic Andro Vujevic Luka Bielen Jaksa Babel department of internal medicine University Hospital Centre ZagrebZagreb 10000Croatia School of medicine University of ZagrebZagreb 10000Croatia

BACKGROUND Solid organ transplantation(SOT)and hematopoietic stem cell transplantation(HSCT)revolutionized the survival and quality of life of patients with malignant diseases,various immunologic,and metabolic disorders or those associated with a significant impairment in a patient's quality of *** To investigate admission causes and treatment outcomes of patients after SOT or HSCT treated in a medical intensive care unit(ICU).METHODS We conducted a single-center,retrospective epidemiological study in the medical ICU at the University Hospital Centre Zagreb,Croatia covering the period from January 1,2018 to December 31,*** The study included 91 patients with either SOT[28 patients(30.8%)]or HSCT[63 patients(69.2%)].The median age was 56(43.2-64.7)years,and 60.4%of the patients were *** with SOT had more comorbidities than patients after HSCT[χ^(2)(5,n=141)=18.513,Py acute respiratory insufficiency in patients following *** rate significantly differed between SOT and HSCT[χ^(2)(1,n=91)=21.767,Py[χ^(2)(1,n=91)=36.803,Py for acute renal replacement therapy did not influence patients'survival[χ^(2)(1,n=91)=0.376,P=0.54].In the subgroup of patients with infection,90%had septic shock,and the majority had positive microbiological samples,mostly Gram-negative *** ICU survival of patients with sepsis/septic shock cumulatively was 15%.The survival of SOT patients with sepsis/shock was 45%.CONCLUSION Patients with SOT or HSCT are frequently admitted to the ICU due to sepsis and septic *** advancements in critical care,the mortality rate of patients with refractory septic shock and multiorgan failure in this patient population is extremely hig

关键词： Liver transplantation Kidney transplantation Hematopoietic stem cell transplantation Critical care Sepsis Septic shock Mortality

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Identification of patients with advanced pancreatic cancer who might benefit from third-line chemotherapy

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 74-83页

作者： Bomi Kim Jaihwan Kim Soomin yang Jinwoo Ahn Kwangrok Jung Jong-Chan Lee Jin-Hyeok Hwang department of internal medicine Seoul National University Bundang HospitalSeoul National University College of MedicineSeongnam 13620South Korea

BACKGROUND Survival rates of patients with advanced pancreatic cancer(APC)have been improved with palliative chemotherapy *** current preferred first-line regimen consists of combination therapy of 5-fluorouracil(5-FU)/leucovorin(LV),irinotecan,and oxaliplatin(FOLFIRINOX)or gemcitabine plus albumin-bound paclitaxel(GNP).After failure of first-line chemotherapy,there are a few options for subsequent therapy including switch to the unused first-line regimen or nanoliposomal irinotecan and 5-FU/***,there are limited studies on the efficacy of third-line chemotherapy after failure of second-line *** To identify patients with APC who might benefit from third-line *** Medical records from a single tertiary hospital were retrospectively reviewed between 2012 and *** study included patients with histologically or cytologically confirmed metastatic or locally APC who underwent first-line FOLFIRINOX or GNP and subsequently received third-line *** survival(OS)after diagnosis and OS after third-line chemotherapy(OS3)were defined as the interval from the diagnosis to all-cause death and the time between the initiation of the third-line chemotherapy to all-cause death,*** A total of 141 patients were *** median patient age at diagnosis was 61.8 years(36.0-86.0),and 54.9%were *** first-line regimen was FOLFIRINOX(67.4%)or GNP(32.6%).The second-line regimen was FOLFIRINOX(27.0%),GNP(52.5%),or other(20.6%).The median OS was 19.0 months,and the median OS3 and progression-free survival after third-line treatment were 15.3 and 7.3 weeks,*** regard to the best tumor response during third-line chemotherapy,1.4%had partial response,24.8%had stable disease,and 59.6%had progressive *** following clinical factors before third-line chemotherapy affected OS3:Good performance status(PS),serum carbohydrate antigen 19-9(CA19-9)levely≥

关键词： Pancreatic cancer Chemotherapy Survival Performance status Carbohydrate antigen 19-9

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Capsule endoscopy:Do we still need it after 24 years of clinical use?

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World Journal of Gastroenterology 2025年第5期31卷 140-147页

作者： Ahmed Tawheed Alaa Ismail Mohab S Amer Osama Elnahas Tawhid Mowafy department of Endemic medicine Faculty of MedicineHelwan UniversityCairo 11795Egypt Faculty of medicine Helwan UniversityCairo 11795Egypt department of Research SMART Company for Research ServicesCairo 11795Egypt department of internal medicine Gardenia Medical CenterDoha 0000Qatar

In this letter,we comment on a recent article published in the World Journal of Gastroenterology by Xiao et al,where the authors aimed to use a deep learning model to automatically detect gastrointestinal lesions during capsule endoscopy(CE).CE was first presented in 2000 and was approved by the Food and Drug Administration in *** indications of CE overlap with those of regular diagnostic ***,in clinical practice,CE is usually used to detect lesions in areas inaccessible to standard endoscopies or in cases of bleeding that might be missed during conventional *** the emergence of CE,many physiological and technical challenges have been faced and *** this letter,we summarize the current challenges and briefly mention the proposed methods to overcome these challenges to answer a central question:Do we still need CE?

关键词： Capsule endoscopy Wireless capsule endoscopy Obscure gastrointestinal bleeding Artificial intelligence in gastroenterology Therapeutic capsule endoscopy

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Fanlian Huazhuo formula:A promising therapeutic approach for metabolic associated steatotic liver disease

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World Journal of Gastroenterology 2025年第1期31卷 167-171页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of Medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305Taiwan Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561Taiwan Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328Taiwan

This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of *** study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and *** editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.

关键词： Fanlian Huazhuo formula Metabolic associated steatotic liver disease Autophagy Lipid metabolism Oxidative stress

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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRyCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neuroscience and Regenerative medicine&department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

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Therapeutic use of music listening in patients undergoing invasive coronary procedures:A meta-analysis

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World Journal of Cardiology 2025年第1期17卷 78-91页

作者： Ahmed Kamal Siddiqi Aimen Shafiq Mushood Ahmed Anusha Anwer Muhammad Talha Maniya Aymen Ahmed Muhammad Azhar Chachar Md Al Hasibuzzaman Division of Cardiothoracic Imaging Department of Radiology and Imaging SciencesEmory UniversityAtlantaGA 30322United States department of medicine Dow University of Health SciencesKarachi 74200Pakistan department of internal medicine Rawalpindi Medical UniversityRawalpindi 74200Pakistan department of internal medicine Dow Medical CollegeDow University of Health SciencesKarachi 74200Pakistan department of medicine Ziauddin Medical UniversityKarachi 74200Pakistan department of medicine Niramoy HospitalPanchagarh 5010Bangladesh department of medicine The First Affiliated Hospital of Ningbo UniversityNingbo 315211Zhejiang ProvinceChina

BACKGROUND Listening to music has been shown to reduce pain and anxiety before,during,and after invasive coronary *** To perform a systematic review and meta-analysis to explore the effect of therapeutic use of music on both,perioperative and postoperative outcomes of invasive coronary *** An exhaustive literature search of 3 electronic databases(MEDLINE,Scopus,Cochrane CENTRAL)was conducted from inception until 10th December *** results of our analyses are presented as standard mean difference(SMD)or weighted mean difference,with 95%CI and pooled using a random effects model.A P valueysis demonstrated that music listening significantly improves post-procedural pain(SMD=-0.78,95%CI:-1.34 to-0.23;P=0.006),anxiety(SMD=-0.86,95%CI:-1.43 to-0.29;P=0.003),heart rate[mean difference(MD)=-3.38,95%CI:-5.51 to-1.25;P=0.002],and systolic blood pressure(MD=-5.89,95%CI:-9.75 to-2.02;P=0.003).There was no significant improvement in diastolic blood pressure(MD=-3.22,95%CI:-6.58 to 0.14;P=0.06)or respiratory rate(MD=-0.97,95%CI:-1.98 to 0.03;P=0.06).CONCLUSION Music listening can be used in healthcare settings for patients undergoing invasive coronary procedures to reduce anxiety levels and improve their physiological parameters.

关键词： Music Music therapy Percutaneous coronary intervention Coronary artery bypass grafting Angiography Anxiety Pain management

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