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

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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Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

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Journal of Geriatric cardiology 2024年第5期21卷 506-522页

作者： Yi XU Tian XU Jia-Cong NONG Xiao-Han KONG Meng-Yao ZHAO Zhi-Jing GAO Yi-Fei WANG Wei YOU Pei-Na MENG Yu-He ZHOU Xiang-Qi WU Zhi-Ming WU Mei-En ZHAN Yan-Qing WANG De-Feng PAN Fei YE department of cardiology Nanjing First HospitalNanjing Hospital Affiliated to Nanjing Medical UniversityNanjing Medical UniversityNanjingChina department of cardiology Clinical Medicine School of Nanjing UniversityNanjingChina department of cardiology Tianchang People’s HospitalTianchangChina department of cardiology the Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent *** A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of *** In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P 1)was significantly higher in the several NR(s NR, defined as RI ≤ 0.85) group than in the non-s NR *** The NR of LCx O is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

关键词： lesions remodeling intravascular

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Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

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World Journal of Gastroenterology 2024年第17期30卷 2321-2331页

作者： Zhi-Peng Lin Xiao-Long Hu Du Chen Da-Bei Huang Xu-Gong Zou Hai Zhong Sheng-Xiang Xu Yuan Chen Xiao-Qun Li Jian Zhang department of interventional Medicine Zhongshan People’s HospitalZhongshan 528400Guangdong ProvinceChina

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than ***,the mechanisms underlying this innovative treatment modality have not been *** To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable *** We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment *** The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,*** surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

关键词： Hepatocellular carcinoma Hepatic arterial infusion chemotherapy Targeted therapy Immunotherapy Adverse events

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The impact of being in the COVID-19 pandemic on in-hospital mortality of non-infected patients aged 80 years and older with ST-elevation myocardial ınfarction

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Journal of Geriatric cardiology 2024年第7期21卷 768-774页

作者： Mustafa Ebik Muhammet Gürdoğan UğurÖzkan department of cardiology Edirne SultanMurat State HospitalEdirneTurkey department of cardiology School of MedicineTrakya UniversityEdirneTurkey

The COVID-19 outbreak in late 2019 was declared a pandemic by the World Health Organization(WHO)on March 12,2020.[1]As of the latest WHO data,COVID-19 has caused over 770 million cases and nearly 7 million deaths worldwide.[2]Hospitalizations due to COVID-19 are correlated with advanced age.[3,4]According to re-ports,individuals over the age of 65 account for 80%of COVID-19-related deaths.[3,4]This is primar-ily due to the increased burden of comorbidity with age.

关键词： infected patients mortality

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Is primary transcatheter aortic valve implantation the new normal?

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Journal of Geriatric cardiology 2024年第4期21卷 458-461页

作者： R.Anantharaman C.Sundar Kamal Kant Jena K.Arun department of cardiology Kauvery HospitalChennaiIndia

Degenerative calcific aortic valve stenosis(AS)is the most common valvular heart disease in elderly.^[1] It is well documented that symptomatic severe AS follows a malignant course leading to cardiogenic shock(CS).

关键词： aortic stenosis implantation

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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(P1).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;P1).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,P1)and a greater incidence of adverse events(94.3%vs 75.4%,P1).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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Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty

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Current Medical Science 2024年第3期44卷 561-567页

作者： Xiang-qi WU Long-bo LI Wei YOU Zhi-ming WU Lei ZHAO Zhi-hui WANG Pei-na MENG Bin LIU Fei YE department of cardiology Nanjing First HospitalNanjing Medical UniversityNanjing210006China department of cardiology The Second Hospital of Jilin UniversityJilin130000China

Objective The study sought to investigate the clinical predictive value of quantitative flow ratio(QFR)for the long-term target vessel failure(TVF)outcome in patients with in-stent restenosis(ISR)by using drug-coated balloon(DCB)treatment after a long-term *** This was a retrospective study.A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were *** QFR of the entire target vessel was measured *** primary endpoint was TVF,including target vessel-cardiac death(TV-CD),target vessel-myocardial infarction(TV-MI),and clinically driven-target vessel revascularization(CD-TVR).Results The follow-up time was 3.09±1.53 years,and 50 patients had *** QFR immediately after percutaneous coronary intervention(PCI)was significantly lower in the TVF group than in the no-TVF *** Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up[hazard ratio(HR):5.15×10−5(6.13×10−8−0.043);P1].Receiver-operating characteristic(ROC)curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925(area under the curve:0.886,95%confidence interval:0.834–0.938;sensitivity:83.40%,specificity:88.00;P1).In addition,QFR≤0.925 post-PCI was strongly correlated with the TVF,including TV-MI and CD-TVR(P1).Conclusion The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty.A lower QFR immediately after PCI was associated with a worse TVF outcome.

关键词： percutaneous coronary intervention in-stent restenosis target vessel failure quantitative flow ratio

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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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Conquer coronary artery perforation with magic hands

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Journal of Geriatric cardiology 2024年第4期21卷 379-386页

作者： Yi-Lun ZOU Jian-Qiang LI Ding-Yu WANG Yong-Tai GONG Li SHENG Yue LI department of cardiology the First Affiliated Hospital of Harbin Medical UniversityHarbinChina

Coronary artery perforation(CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the perforation. The conventional method for addressing the perforation of large vessels involves the placement of a covered stent, while the perforation of distal and collateral vessels is typically managed using coils, autologous skin, subcutaneous fat, microspheres, gelatin sponge, thrombin or other substances. However, the above techniques have certain limitations and are not applicable in all scenarios. Our team has developed a range of innovative strategies for effectively managing CAP. This article provides an insightful review of the various tips and tricks for the treatment of CAP.

关键词： coronary sponge perforation

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