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Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3481-3495页

作者： Meng-Xuan Zuo Chao An Yu-Zhe Cao Jia-Yu Pan Lu-Ping Xie Xin-Jing Yang Wang Li Pei-Hong Wu Department of Minimally Invasive interventional Therapy Sun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Department of interventional Ultrasound Chinese General PLA HospitalBeijing 100853China Department of Medical Imaging and interventional Radiology Sun Yatsen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still *** To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for *** From January 2018 to March 2022,217 Ad-HCC patients were retrospectively *** them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance *** survival(OS)was compared using the Kaplan-Meier curve with the log-rank *** overall objective response rate(ORR)and major complications were also *** After PSM,82 patients were included both the T-A group and the T-M *** ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

关键词： Hepatic arterial infusion chemotherapy Hepatocellular carcinoma Molecular targeting agent Programmed cell death protein 1 inhibitors Microwave ablation

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Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

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World Journal of Gastroenterology 2024年第4期30卷 318-331页

作者： Yu-Zhe Cao Guang-Lei Zheng Tian-Qi Zhang Hong-Yan Shao Jia-Yu Pan Zi-Lin Huang Meng-Xuan Zuo Department of Minimally Invasive interventional Therapy Sun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Department of Minimally Invasive interventional Therapy State Key Laboratory of Oncology in South ChinaGuangzhou 510060Guangdong ProvinceChina Department of Minimally Invasive interventional Therapy Guangdong Provincial Clinical Research Center for CancerGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating ***,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are *** To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world *** Several electronic databases were searched to identify eligible randomized controlled trials for this ***-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were *** was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer center from January 2018 to April *** score matching(PSM)was performed to balance the bias between the *** Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the *** A total of 13 randomized controlled trials were *** alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the *** triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for *** findings confirm that triple therapy is more effective for uHCC patients than AIPB.

关键词： Unresectable hepatocellular carcinoma Hepatic arterial infusion chemotherapy Angiogenesis inhibitors Programmed cell death protein 1 Programmed death ligand 1

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Gene expression profiles contribute to robustly predicting prognosis in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 593-596页

作者： Long Liu Yuhui Wang Yuyuan Zhang Siyuan Weng Hui Xu Zaoqu Liu Xinwei Han Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Prenatal Diagnosis center The Third Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China interventional Institute of Zhengzhou University ZhengzhouHenan 450052China interventional Treatment and Clinical Research center of Henan Province ZhengzhouHenan 450052China

Hepatocellular carcinoma(HCC)is characterized by both inter-and intra-tumor heterogeneity and has distinct clinical outcomes.1 A promising clinical tool to perform patient stratification,prognosis evaluation,and treatment recommendations is ***,we enrolled a total of 1595 tumor patients from 13 independent cohorts,including seven cohorts with survival data,four cohorts with immunotherapy information,and two cohorts with transcatheter arterial chemoembolization(TACE)and Sorafenib information,respectively(Table S1).Using 96 algorithms combinations derived from 10 popular machinelearning approaches,a novel framework was constructed and described in Figure ***,a total of 26 stable consensus prognostic genes were screened in seven cohorts harboring complete survival information via univariate Cox regression analysis(Fig.S2A).

关键词： prognosis clinical arterial

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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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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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Cytochrome P45026A1 Contributes to the Maintenance of Neuropathic pain

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Neuroscience Bulletin 2024年第3期40卷 293-309页

作者： De-Li Cao Ling-Jie Ma Bao-Chun Jiang Qiang Gu Yong-Jing Gao Institute of pain Medicine and Special Environmental Medicine Co-innovation Center of NeuroregenerationNantong UniversityNantong226019China Nantong University Medical School Nantong226001China Department of pain Management The Affiliated Hospital of Nantong UniversityNantong226001China

The cytochrome P450 proteins(CYP450s)have been implicated in catalyzing numerous important biological reactions and contribute to a variety of ***26A1,a member of the CYP450 family,carries out the oxidative metabolism of retinoic acid(RA),the active metabolite of vitamin *** we report that CYP26A1 was dramatically upregulated in the spinal cord after spinal nerve ligation(SNL).CYP26A1 was mainly expressed in spinal neurons and *** analysis displayed that the content of all-trans-RA(at-RA),the substrate of CYP26A1,was reduced in the spinal cord on day 7 after *** of CYP26A1 by siRNA or inhibition of CYP26A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance phase of neuropathic *** also reduced SNL-induced glial activation and proinflammatory cytokine production but increased anti-inflammatory cytokine(IL-10)*** RA receptors RARα,RXRβ,and RXRγwere expressed in spinal neurons and glial *** promoter of Il-10 has several binding sites for RA receptors,and at-RA directly increased Il-10 mRNA expression in ***,intrathecal IL-10 attenuated SNL-induced neuropathic pain and reduced the activation of astrocytes and ***,the inhibition of CYP26A1-mediated at-RA catabolism alleviates SNL-induced neuropathic pain by promoting the expression of IL-10 and suppressing glial ***26A1 may be a potential therapeutic target for the treatment of neuropathic pain.

关键词： CYP26A1 Microglia Astrocytes ERK P38 IL-10 Neuropathic pain

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Ultrasound-guided sphenopalatine ganglion block for effective analgesia during awake fiberoptic nasotracheal intubation: A case report

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World Journal of Clinical Cases 2024年第14期12卷 2451-2456页

作者： Hangil Kang Seongjae Park Yehun Jin Department of Anesthesiology and pain Medicine National Cancer CenterGoyang-si 10408Gyeonggi-doSouth Korea

BACKGROUND Awake fiberoptic nasotracheal intubation(AFNI)is the preferred airway ma-nagement strategy for patients with difficult ***,this procedure can cause significant physical and psychological *** case report explores the application of a sphenopalatine ganglion(SPG)block as an alternative anal-gesic modality to mitigate the discomfort associated with *** SUMMARY A 63-year-old female with a history of right maxillary osteosarcoma underwent craniotomy for a suspected malignant brain *** patient’s medical history included prior surgery,chemotherapy,and radiation therapy,resulting in signi-ficant jaw impairment and limited neck *** the anticipated air-way challenges,AFNI was planned.A SPG block was performed under real-time ultrasound guidance,providing effective analgesia during nasotracheal *** The SPG block represents a promising analgesic approach in AFNI,offering po-tential benefits in alleviating pain involving the nasal and nasopharyngeal regions as well as improving patient cooperation.

关键词： Sphenopalatine ganglion block Nerve block Regional anesthesia Analgesia Awake fiberoptic nasotracheal intubation Case report

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Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake

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Stroke & Vascular Neurology 2024年第4期9卷 390-398页

作者： Gabriel Broocks Lukas Meyer Uta Hanning Tobias Djamsched Faizy Matthias Bechstein Helge Kniep Noel Van Horn Gerhard Schön Ewgenia Barow Götz Thomalla Jens Fiehler Andre Kemmling Department of Diagnostic and interventional Neuroradiology University Medical Center Hamburg-EppendorfHamburgGermany Department of Medical Biometry and Epidemiology University Medical Center Hamburg EppendorfHamburgGermany Department of Neurology University Medical Center Hamburg-EppendorfHamburgGermany Department of Neuroradiology University MarburgMarburgGermany

Background and purpose In wake-up stroke,CT-based quantitative net water uptake(NWU)might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase(IVT).An important complication after IVT is symptomatic intracerebral haemorrhage(sICH).As NWU directly implies ischaemic lesion progression,reflecting blood-brain barrier injury,we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown *** Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October *** NWU was assessed on baseline *** primary endpoint was *** association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting(IPW)*** A total of 88 patients were included,of which 46 patients(52.3%)received *** median NWU was 10.7%(IQR:5.1–17.7).The proportion of patients with any haemorrhage and sICH were 35.2%and 13.6%.NWU at baseline was significantly higher in patients with sICH(19.1%vs 9.6%,p<0.0001)and the median Alberta Stroke Program Early CT Score(ASPECTS)was lower(5 vs 8,p<0.0001).Following IPW,there was no association between IVT and sICH in unadjusted ***,after adjusting for ASPECTS and NWU,there was a significant association between IVT administration and sICH(14.6%,95%CI:3.3%to 25.6%,p<0.01).Conclusion In patients with ischaemic stroke with unknown onset,the combination of high NWU with IVT is directly linked to higher rates of *** ASPECTS for evaluating the extent of the early infarct lesion,quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke.

关键词： throm thrombolysis high

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Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRβ

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Frontiers of Medicine 2024年第3期18卷 465-483页

作者： Fei Xu Han Chen Changyi Zhou Tongtong Zang Rui Wang Shutong Shen Chaofu Li Yue Yu Zhiqiang Pei Li Shen Juying Qian Junbo Ge Department of Cardiology and Laboratory of Heart Valve Disease West China HospitalSichuan UniversityChengdu610041China Department of Cardiology Zhongshan HospitalFudan UniversityResearch Unit of Cardiovascular Techniques and DevicesChinese Academy of Medical SciencesShanghai200032China Shanghai Institute of Cardiovascular Diseases Shanghai200032China National Clinical Research center for interventional Medicine&Shanghai Clinical Research center for interventional Medicine(19MC1910300) Shanghai200032China

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular *** smooth muscle cells(VSMCs),the main components of atherosclerotic plaque,switch from contractile to synthetic phenotypes during *** is crucial in regulating VSMC phenotypes in atherosclerosis,and it can be reversely regulated by ***,the specific effects of deubiquitinases on atherosclerosis have not been thoroughly *** this study,RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases,which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype *** in vivo studies using Apoe−/−mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque ***,VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in *** RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation,adhesion,and *** spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ***,we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRβwith its catalytic triad,thereby reducing the K48-linked ubiquitylation of PDGFRβ.Inhibiting OTUB1 in VSMCs could promote PDGFRβdegradation via the ubiquitin–proteasome pathway,so it was beneficial in preventing VSMCs’phenotype *** findings revealed that knocking down OTUB1 ameliorated VSMCs’phenotype switch and atherosclerosis progression,indicating that OTUB1 could be a valuable translational therapeutic target in the future.

关键词： atherosclerosis vascular smooth muscle cell ubiquitylation deubiquitinase OTUB1 PDGFRβ

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Silencing of peroxiredoxin 2 suppresses proliferation and Wnt/β-catenin pathway,and induces senescence in hepatocellular carcinoma

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Oncology Research 2024年第1期32卷 213-226页

作者： XUEGANG YANG XIANHONG XIANG GUOHUI XU SHI ZHOU TIANZHI AN ZHI HUANG Department of interventional Radiology Sichuan Cancer Hospital and InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaRadiation Oncology Key Laboratory of Sichuan ProvinceChengdu610041China Department of interventional Radiology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou510080China Department of interventional Radiology Affiliated Hospital of Guizhou Medical UniversityGuiyang550004China School of Basic Medical Science Guizhou Medical UniversityGuiyang550002China

Hepatocellular carcinoma(HCC),a common malignancy worldwide,still lacks effective clinical *** study aimed to investigate the oncogenes that affect the progression of HCC and their possible *** our study,we initially confirmed a higher level of PRDX2 in the bile of HCC patients compared to those with choledocholithiasis by 2-DE,LC-MS,and ***,we demonstrated the high expression of peroxiredoxin 2(PRDX2)in HCC based on the TCGA database and clinical sample ***,PRDX2 overexpression enhanced the viability of HCC *** PRDX2 silencing induced senescence of HCC *** vivo,knockdown of PRDX2 significantly reduced the weight of xenograft ***2 also was found to activate the Wnt/β-catenin pathway by inducingβ-catenin nuclear ***,we proved that silencing PRDX2 could inhibit proliferation and Wnt/β-catenin pathway while promoting senescence in HCC cells.

关键词： Peroxiredoxin 2 Hepatocellular carcinoma Wnt/β-catenin pathway Senescence Proliferation

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