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Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu Shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-Xiu Qin Hepatobiliary Surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina Center of interventional radiology and Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical Sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise intervention of Digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor *** cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated *** the dysregulated nervous systems might represent a novel strategy for cancer ***,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely *** staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC ***93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC *** all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

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Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 361-369页

作者： Zhong-Xing Shi Chang-Fu Li Li-Feng Zhao Zhong-Qi Sun Li-Ming Cui Yan-Jie Xin Dong-Qing Wang Tan-Rong Kang Hui-Jie Jiang department of interventional radiology the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China department of Digestive Medicine Daqing Longnan HospitalDaqing 163453China department of radiology Daqing Longnan HospitalDaqing 163453China department of radiology the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment *** study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient ***:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were *** tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were *** radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was *** predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration ***:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s *** were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment *** predicted treatment response also allowed for significant discrimination of Kaplan-Meier *** Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interva

关键词： Hepatocellular carcinoma Transarterial chemoembolization Radiomics Treatment response Prediction

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Shrinking fat,healing liver:unlocking the metabolic dysfunction associated steatohepatitis puzzle

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 132-135页

作者： Sudhakar K.Venkatesh Ilkay S.Idilman Jiahui Li Meng Yin department of radiology Mayo ClinicRochesterMNUSA department of radiology Hacettepe UniversityAnkaraTurkey

Metabolic dysfunction associated steatohepatitis(MASH)is a silent epidemic,hiding in the shadows of obesity,and often silently advancing towards the grave complication of *** distinction between MASH and simple hepatic steatosis,which is under the spectrum of metabolic dysfunction-associated steatotic liver disease(MASLD),is highly desired as it provides critical information about the prognosis of the *** indicators,such as fibrosis-4(FIB-4)index and nonalcoholic fatty liver disease(NAFLD)fibrosis score that includes conventional laboratory data and clinical parameters.

关键词： Proton density fat fraction(PDFF) metabolic dysfunction associated steatohepatitis(MASH) deep subcutaneous fat

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Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for≥5 cm hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2793-2803页

作者： Jie-Fei Cheng Qiu-Lian Sun Ling Tang Xin-Jian Xu Xiang-Zhong Huang department of radiology The Fifth People’s Hospital of TaizhouTaizhou 225300Jiangsu ProvinceChina department of radiology The Fifth People’s Hospital of SuzhouSuzhou 215100Jiangsu ProvinceChina department of radiology The Fourth People’s Hospital of TaizhouTaizhou 225300Jiangsu ProvinceChina department of interventional radiology Jiangyin People HospitalJiangyin 214400Jiangsu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)ranks sixth globally in cancer incidence and third in mortality ***,over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations,poor physical condition,and limited organ availability upon *** guidelines endorse transarterial chemoembolization(TACE)as the frontline treatment for intermediate to advanced-stage ***(CRA)is an emerging local ablative therapy increasingly used in HCC *** studies suggest that combining CRA with TACE offers complementary and synergistic effects,potentially improving long-term survival ***,the superiority of combined TACE+CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further *** To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of≥5 *** PubMed,EMBASE,Cochrane Library,CNKI,Wanfang,and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July ***-analysis was performed using RevMan 5.3 *** After screening according to the inclusion and exclusion criteria,6 articles were included,including 2 randomized controlled trials and 4 nonrandomized controlled trials,with a total of 575 patients included in the *** results showed that the objective response rate[odds ratio(OR)=2.56,95%confidence interval(CI):1.66-3.96,P<0.0001],disease control rate(OR=3.03,95%CI:1.88-4.89,P<0.00001),1-year survival rate(OR=3.79,95%CI:2.50-5.76,P<0.00001),2-year survival rate(OR=2.34,95%CI:1.43-3.85,P=0.0008),and 3-year survival rate(OR=3.34,95%CI:1.61-6.94,P=0.001)were all superior to those of the control group;the postoperative decrease in alpha-fetoprotein value(OR=295.53,95%CI:250.22-340.85,P<0.0001),the postoperative increase in CD4 value(OR=10.59,95%CI:8.78-12.40,P<0.00001),and the postoperative decrease in

关键词： Hepatic cancer Cryoablation Chemoembolization Transarterial chemoembolization Meta analysis

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Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

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World Journal of Gastroenterology 2024年第31期30卷 3668-3679页

作者： Hong-Wei Zhao Jin-Long Zhang Fu-Quan Liu Zhen-Dong Yue Lei Wang Yu Zhang Cheng-Bin Dong Zhen-Chang Wang department of radiology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China department of radiology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China department of interventional radiology Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver *** GM composition is diverse and associated with different etiologies of liver ***,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in ***,understanding the role of GM alterations in patients with HBV infection-related PH is *** To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)*** This was a prospective,observational clinical *** were 30 patients(with a 100%technical success rate)recruited in the present *** with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were *** samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon *** One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE *** was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE *** Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated *** microbiome therapies may be useful for preventing and trea

关键词： Transjugular intrahepatic portosystemic shunt Hepatic encephalopathy Gut microbiota Hepatitis B virus Portal hypertension

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New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 15-24页

作者： Jian-Jian Chen Zhi-Cheng Jin Biao Luo Yu-Qing Wang Rui Li Hai-Dong Zhu Gao-Jun Teng Center of interventional radiology&Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast UniversityNanjingJiangsuChina

Background and Aims:Several first-line immune checkpoint inhibitor(ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma(uHCC).This network meta-analysis(NMA)aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for ***:A comprehensive literature search was performed in various databases from database inception to May *** phase 3 trials evaluating first-line single-agent ICIs,molecular-target agents(MTAs),or their combinations in uHCC were *** main endpoints were overall survival(OS)and progression-free survival(PFS).Pooled effect estimates were calculated using a random effects model within the frequentist *** analyses based on etiology were also ***:Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were *** with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305[hazard ratio(HR):1.16;95%confidence interval(CI):0.80–1.68]and camrelizumab plus apatinib(HR:1.06;95%CI:0.75–1.51).The combination therapies,apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS,had higher P-score than single-agent MTAs or *** survival benefits were associated with a high risk of adverse events leading to treatment *** proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages(R2=0.8039,p=0.0155).Conclusion:This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for *** optimal treatment algorithms should consider efficacy,safety,and etiology.

关键词： Hepatocellular carcinoma Systemic therapy Immunotherapy Molecular targeted therapy Tyrosine protein kinase inhibitors Overall survival

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Fabrication of a 25.2 T NMR magnet for an extreme condition user facility in China

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National Science Review 2024年第7期11卷 62-64页

作者： Hui Han Yun Shang MRI Research Institute Department of RadiologyWeill Medical College of Cornell University

An ultra-high field magnet（>20 T）is desirable for studying the characteristics of new materials under extreme magnetic conditions [1]. Additionally,such field strength will result in resonance frequencies close to or greater than 1 GHz when applied to the study of1H signals from biomolecules by nuclear magnetic resonance（NMR）,which will lead to a higher signal-to-noise ratio, better sensitivity and a higher spectral resolution due to increased chemical shift dispersion [2].

关键词： NMR double pancake high temperature superconducting magnet ultra-high field

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Self-fueling ferroptosis-inducing microreactors based on p H-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy

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National Science Review 2024年第1期11卷 74-85页

作者： Chunjie Wang Lei Zhang Zhijuan Yang Dongxu Zhao Zheng Deng Jialu Xu Yumin Wu Yu Hao Ziliang Dong Liangzhu Feng Zhuang Liu Institute of Functional Nano & Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices Soochow University Center of interventional radiology & Vascular Surgery Department of Radiology Zhongda Hospital Medical School Southeast University department of interventional radiology The First Afflliated Hospital of Soochow University

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma(HCC) via transarterial chemoembolization(TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment. Herein, a stable water-in-oil Lipiodol Pickering emulsion(LPE) stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase(LOX). The obtained LOX-loaded CaCO3&hemin-stabilized LPE(LHCa-LPE) showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids(PUFAs), a main component of Lipiodol, to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin, thus inducing ferroptosis of cancer cells. As a result, such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats. This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors, which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.

关键词： CaCO3 nanoparticles Pickering emulsion ferroptosis lipid peroxidation transarterial ferro-embolization

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Comparative study between Embosphere®and Marine gel®as embolic agents for chemoembolization of hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 102-109页

作者： Hyo-Cheol Kim Jin Woo Choi department of radiology Seoul National University HospitalSeoul 03080South Korea

BACKGROUND While gelatin sponge particles and calibrated microspheres are commonly used as embolic materials in conventional transarterial chemoembolization(cTACE),direct comparisons between these embolic agents are *** To compare the efficacy and safety of superselective cTACE using Embosphere®or Marine gel®in patients with early-stage hepatocellular carcinoma(HCC).METHODS This retrospective study included 70 patients with small(<4 cm)HCC who underwent cTACE with Embosphere®(n=33)or Marine gel®(n=37)as the embolic agent at a single center between March 2021 and July *** radiologic images and clinical data were retrospectively reviewed,with an emphasis on tumor response,procedure-related complications,and local tumor *** primary index tumor was assessed on a 1-mo follow-up image,and local progression-free survival was obtained using the Kaplan-Meier method and was compared by the log-rank *** The median tumor size of both groups was 1.5 cm,and 69 patients achieved a complete response one month after *** cumulative local recurrence rate at 12 mo was 15.5%in the Embosphere®group and 14.4%in the Marine gel®*** local progression-free survival was not significantly different between the two groups(P=0.83).In the multivariate analysis,high serum alphafetoprotein was the only significant poor prognostic factor for local tumor progression(P=0.01).Postembolization syndrome occurred in 36.4%of the Embosphere®group and 35.1%of the Marine gel®group,and there were no cases of biloma,biliary duct dilation,or liver abscess in either *** Calibrated gelatin sponge particles(Marine gel®)and calibrated microspheres(Embosphere®)have similar outcomes in terms of tumor response for superselective cTACE of small HCC.

关键词： Hepatocellular carcinoma Chemoembolization Temporary embolic material Permanent embolic material Tumor response

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Complementary comments on diagnosis,severity and prognosis prediction of acute pancreatitis

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World Journal of Gastroenterology 2024年第1期30卷 108-111页

作者： Muhsin Ozgun Ozturk Sonay Aydin department of radiology Erzincan Binali Yildirim UniversityErzincan 24000Turkey

The radiological differential diagnosis of acute pancreatitis includes diffuse pancreatic lymphoma,diffuse autoimmune pancreatitis and groove located mass lesions that may mimic groove *** energy computed tomography and diffusion weighted magnetic resonance imaging are useful in the early diagnosis of acute pancreatitis,and dual energy computed tomography is also useful in severity assessment and prognosis *** off necrosis is an important complication in terms of prognosis,and it is important to know its radiological findings and distinguish it from pseudocyst.

关键词： Acute pancreatitis Computed tomography Diffusion weighted imaging Dual energy computed tomography Walled off necrosis

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