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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

Hepatocellular carcinoma with macrovascular invasion:need a personalized medicine for this complicated event

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 188-190页

作者： Hyeonseung Hwang Ju Hyun Shim Jin Hyoung Kim department of radiology and Research Institute of radiology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea department of Gastroenterology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea

Hepatocellular carcinoma(HCC)is a hypervascular tumor and has a tendency to invade portal vein(PV)or hepatic vein(HV).HCC with macrovascular invasion(MVI)is associated with poor prognosis(1).HCC invasion of PV can lead to rapid intrahepatic tumor *** addition,portal vein tumor thrombus(PVTT)may result in deterioration of hepatic function,as well as increased risk of portal hypertensive complications(2).HCC invasion of HV is associated with increased risk of systemic ***.

关键词： invasion hepatic hypertensive

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

NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Women&Children Research center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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Oncology Research 2024年第2期32卷 309-323页

作者： BEHROOZ JOHARI MILAD PARVINZAD LEILAN MAHMOUD GHARBAVI YOUSEF MORTAZAVI ALI SHARAFI HAMED REZAEEJAM department of medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Zanjan Pharmaceutical Biotechnology Research center Zanjan University of Medical SciencesZanjanIran Nanotechnology Research center Ahvaz Jundishapur University of Medical SciencesAhvazIran department of radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell *** and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 *** nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical ***,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer *** anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized *** revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation *** can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

关键词： Combinational therapy Antisense therapy Myc signaling pathway Niosomes Radiation therapy SeNPs

Multilocular thymic cysts can be easily misdiagnosed as malignant tumor on computer tomography:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1474-1480页

作者： Jun Sun Qing-Ning Yang Yi Guo Ping Zeng Long-Yan Ma Ling-Wen Kong Bo-Ying Zhao Chuan-Ming Li department of radiology Chongqing University Central HospitalChongqing Emergency Medical CenterChongqing 400014China department of Pathology Chongqing University Central HospitalChongqing Emergency Medical CenterChongqing 400014China department of Cardiothoracic Surgery Chongqing University Central HospitalChongqing Emergency Medical CenterChongqing 400014China

BACKGROUND Multilocular thymic cyst(MTC)is a rare mediastinal lesion which is considered to occur in the process of acquired *** is usually characterized by well-defined cystic density and is filled with transparent *** SUMMARY We report on a 39-year-old male with a cystic-solid mass in the anterior *** tomography(CT)imaging showed that the mass was irregular with unclear *** injection of contrast agent,there was a slight enhancement of stripes and *** to CT findings,it was diagnosed as thymic *** After surgery,MTC accompanied by bleeding and infection was confirmed by pathological *** main lesson of this case was that malignant thymic tumor and MTC of the anterior mediastinum sometimes exhibit similar CT *** is necessary in clinical work to avoid misdiagnosis.

关键词： Multilocular thymic cyst Computer tomography Misdiagnosis Hemorrhage Infection Case report

Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination

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Neural Regeneration Research 2024年第3期19卷 493-494页

作者： Melissa Schepers Tim Vanmierlo department of Neuroscience Biomedical Research InstituteFaculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium department of Psychiatry and Neuropsychology School for Mental Health and NeuroscienceMaastricht UniversityMaastrichtNetherlands university MS center(UMSC)Hasselt-Pelt HasseltBelgium

In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is ***,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon *** to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in ***,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.

关键词： impaired inflammation Marie

Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation

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Chinese Journal of Natural Medicines 2024年第5期22卷 387-401页

作者： FENG Qianwen SUN Lu Muhammad Jibran Sualeh ZHAO Qingli ZHAO Songji CUI Zhengguo INADERA Hidekuni department of Public Health Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan department of Pediatric Cardiology Heart CenterGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510000China department of Basic medical Sciences College of MedicineUniversity of SharjahSharjah 57545United Arab Emirates department of radiology Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Advanced Clinical Research center Fukushima Global Medical Science CenterFukushima Medical UniversityFukushima CityFukushima 960-8074Japan department of Environmental Health School of Medical SciencesUniversity of FukuiFukui 910-8580Japan

Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal *** its notable properties,the anti-cancer effects of Her have remained largely *** this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis ***,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 *** findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy ***,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter ***,we determined that Her did not prevent the fusion of autophagosomes and ***,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal *** use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome *** application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell *** observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell *** study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell *** insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic st

关键词： Hernandezine Apoptosis Mitophagy Autophagic flux Lysosome Noncanonical autophagy

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

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Oncology Research 2024年第1期32卷 101-125页

作者： ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI department of medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Nanotechnology Research center Ahvaz Jundishapur University of Medical SciencesAhvazIran Zanjan Pharmaceutical Biotechnology Research center Zanjan University of Medical SciencesZanjanIran department of Pharmaceutical Biotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Molecular Medicine department Biotechnology Research CenterPasteur Institute of IranPasteur AvenueTehranIran department of radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer *** decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics *** were loaded on the synthesized Se@BSA@Chi-MTX *** physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis ***,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell *** results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,*** results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of *** results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/*** ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic *** targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the *** results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP *** nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关键词： Chemoradiotherapy Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer