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pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

Acta Pharmaceutica Sinica B 2024年第2期14卷 781-794页

作者： Shuai Guo Chunhui Li Changrong Wang Xiaowen Cao Xinyue Liu xing-jie liang Yuanyu Huang Yuhua Weng School of Medical Technology Advanced Research Institute of Multidisciplinary ScienceSchool of Life ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China School of Pharmacy Shandong New Drug Loading&Release Technology and Preparation Engineering LaboratoryBinzhou Medical UniversityYantai 264003China School of Ophthalmology and Optometry School of Biomedical EngineeringThe Eye HospitalWenzhou Medical UniversityWenzhou 325027China Chinese Academy of Sciences(CAS) Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

Small interfering RNA(siRNA)has a promising future in the treatment of ocular diseases due to its high efficiency,specificity,and low toxicity in inhibiting the expression of target genes and proteins.However,due to the unique anatomical structure of the eye and various barriers,delivering nucleic acids to the retina remains a significant challenge.In this study,we rationally design PACD,an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block(A),a siRNA binding block(B)and a pH-responsive block(C).PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing.By evaluating its pH-responsive activity,gene silencing efficiency in retinal cells,intraocular distribution,and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis,we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina.We are surprised to discover that,the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency,excellent gene silencing,and inhibit retinal angiogenesis.Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

关键词： SiRNA Oculardeliverysystem Block polymer Endosomalescape Retinal neovascularization Blood-retinal barrier VEGFA Safety

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Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

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World Journal of Clinical Cases 2024年第6期12卷 1174-1181页

作者： Yu-jie Qin Ting Gao xing-Nian Zhou Ming-liang Cheng Hong Li Clinical Medicine School of Guizhou Medical University Guiyang 550025Guizhou ProvinceChina Department of Pathology The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina Department of Infectious Diseases Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina Department of Infectious Diseases Guizhou Provincial People's HospitalGuiyang 550025Guizhou ProvinceChina

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

关键词： Overlap syndrome Autoimmune hepatitis Primary biliary cholangitis Primary sclerosing cholangitis Autoimmune thyroid disease Case report

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Kinetic-Thermodynamic Promotion Engineering toward High-Density Hierarchical and Zn-Doping Activity-Enhancing ZnNiO@CF for High-Capacity Desalination

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Nano-Micro Letters 2024年第8期16卷 35-50页

作者： jie Ma Siyang xing Yabo Wang Jinhu Yang Fei Yu College of Marine Ecology and Environment Shanghai Ocean University201306 ShanghaiPeople’s Republic of China School of Civil Engineering Kashi University844000 KashiPeople’s Republic of China Research Center for Environmental Functional Materials College of Environmental Science and EngineeringTongji University1239 Siping Road200092 ShanghaiPeople’s Republic of China School of Chemical Science and Engineering Tongji University1239 Siping Road200092 ShanghaiPeople’s Republic of China Department of Energy Environmental&Chemical EngineeringWashington University in St.LouisSt.LouisMO 63130USA

Despite the promising potential of transition metal oxides(TMOs)as capacitive deionization(CDI)electrodes,the actual capacity of TMOs electrodes for sodium storage is significantly lower than the theoretical capacity,posing a major obstacle.Herein,we prepared the kinetically favorable Zn_(x)Ni_(1−x)O electrode in situ growth on carbon felt(Zn_(x)Ni_(1−x)O@CF)through constraining the rate of OH^(−)generation in the hydrothermal method.Zn_(x)Ni_(1−x)O@CF exhibited a high-density hierarchical nanosheet structure with three-dimensional open pores,benefitting the ion transport/electron transfer.And tuning the moderate amount of redox-inert Zn-doping can enhance surface electroactive sites,actual activity of redox-active Ni species,and lower adsorption energy,promoting the adsorption kinetic and thermodynamic of the Zn_(0.2)Ni_(0.8)O@CF.Benefitting from the kinetic-thermodynamic facilitation mechanism,Zn_(0.2)Ni_(0.8)O@CF achieved ultrahigh desalination capacity(128.9 mgNaCl g^(-1)),ultra-low energy consumption(0.164 kW h kgNaCl^(-1)),high salt removal rate(1.21 mgNaCl g^(-1) min^(-1)),and good cyclability.The thermodynamic facilitation and Na^(+)intercalation mechanism of Zn_(0.2)Ni_(0.8)O@CF are identified by the density functional theory calculations and electrochemical quartz crystal microbalance with dissipation monitoring,respectively.This research provides new insights into controlling electrochemically favorable morphology and demonstrates that Zn-doping,which is redox-inert,is essential for enhancing the electrochemical performance of CDI electrodes.

关键词： Zinc-nickel metal oxide High-density hierarchical Capacitive deionization Zinc-doping

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Research progress on venous thrombosis development in patients with malignant tumors

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World Journal of Clinical Cases 2024年第11期12卷 1900-1908页

作者： Teng-Fei Wang Qian Chen jie Deng Shi-liang Li Yuan Xu Si-xing Ma Department of Vascular Surgery The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina Department of Organ Transplantation The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

The coexistence of venous thromboembolism(VTE)within patients with cancer,known as cancer-associated thrombosis(CAT),stands as a prominent cause of mortality in this population.Over recent years,the incidence of VTE has demonstrated a steady increase across diverse tumor types,influenced by several factors such as patient management,tumor-specific risks,and treatment-related aspects.Furthermore,mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes.We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT.This review elucidates the risks,mechanisms,reliable markers,and risk assessment methodologies that can significantly guide effective interventions in clinical practice.

关键词： Malignant tumor Venous thromboembolism Cancer-associated thrombosis Research progress

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Sarcopenia in cirrhotic patients: Does frailty matter while waiting for a liver transplant?

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 257-259页

作者： xing-jie Li Kang He Division of Transplant Surgery Mayo Clinic ArizonaPhoenixAZ 85054United States Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

Sarcopenia reflects patient frailty and should be routinely assessed due to its high prevalence in cirrhotic patients awaiting liver transplants.Pre-transplant nutritional optimization should be tailored for patients with a definitive diagnosis of sarcopenia,therefore improving functional status at transplant and reducing posttransplant mortality.Hepatologists and transplant surgeons should have raised awareness regarding sarcopenia and the reflected frailty that hinder posttransplant outcomes.The policymakers should also take into account when modifying the organ allocation model that sarcopenia or frailty might become a decisive factor in allocating organs for cirrhotic patients,in order to ensure post-transplant survival and quality of life.

关键词： Sarcopenia Liver transplant Organ allocation policy Cirrhosis Frailty

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A visual modeling method for spatiotemporal and multidimensional features in epidemiological analysis:Applied COVID-19 aggregated datasets

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Computational Visual Media 2024年第1期10卷 161-186页

作者： Yu Dong Christy jie liang Yi Chen jie Hua School of Computer Science University of Technology SydneySydneyNSW2007Australia Beijing Key Laboratory of Big Data Technology for Food Safety Beijing Technology and Business UniversityBeijing100048China

The visual modeling method enables flexible interactions with rich graphical depictions of data and supports the exploration of the complexities of epidemiological analysis.However,most epidemiology visualizations do not support the combined analysis of objective factors that might influence the transmission situation,resulting in a lack of quantitative and qualitative evidence.To address this issue,we developed a portrait-based visual modeling method called+msRNAer.This method considers the spatiotemporal features of virus transmission patterns and multidimensional features of objective risk factors in communities,enabling portrait-based exploration and comparison in epidemiological analysis.We applied+msRNAer to aggregate COVID-19-related datasets in New South Wales,Australia,combining COVID-19 case number trends,geo-information,intervention events,and expert-supervised risk factors extracted from local government area-based censuses.We perfected the+msRNAer workflow with collaborative views and evaluated its feasibility,effectiveness,and usefulness through one user study and three subject-driven case studies.Positive feedback from experts indicates that+msRNAer provides a general understanding for analyzing comprehension that not only compares relationships between cases in time-varying and risk factors through portraits but also supports navigation in fundamental geographical,timeline,and other factor comparisons.By adopting interactions,experts discovered functional and practical implications for potential patterns of long-standing community factors regarding the vulnerability faced by the pandemic.Experts confirmed that+msRNAer is expected to deliver visual modeling benefits with spatiotemporal and multidimensional features in other epidemiological analysis scenarios.

关键词： visual modeling epidemiological analysis spatiotemporal multidimensional COVID-19

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A deep learning model based on contrast-enhanced computed tomography for differential diagnosis of gallbladder carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 376-384页

作者： Fei Xiang Qing-Tao Meng Jing-Jing Deng jie Wang Xiao-Yuan liang xing-Yu Liu Sheng Yan Department of Hepatobiliary Pancreatic Surgery Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Radiology Affiliated Chuzhou First People’s HospitalAnhui Medical UniversityChuzhou 239000China

Background:Gallbladder carcinoma(GBC)is highly malignant,and its early diagnosis remains difficult.This study aimed to develop a deep learning model based on contrast-enhanced computed tomography(CT)images to assist radiologists in identifying GBC.Methods:We retrospectively enrolled 278 patients with gallbladder lesions(>10 mm)who underwent contrast-enhanced CT and cholecystectomy and divided them into the training(n=194)and validation(n=84)datasets.The deep learning model was developed based on ResNet50 network.Radiomics and clinical models were built based on support vector machine(SVM)method.We comprehensively compared the performance of deep learning,radiomics,clinical models,and three radiologists.Results:Three radiomics features including LoG_3.0 gray-level size zone matrix zone variance,HHL firstorder kurtosis,and LHL gray-level co-occurrence matrix dependence variance were significantly different between benign gallbladder lesions and GBC,and were selected for developing radiomics model.Multivariate regression analysis revealed that age≥65 years[odds ratios(OR)=4.4,95%confidence interval(CI):2.1-9.1,P37 U/mL(OR=4.0,95%CI:1.6-10.0,P=0.003)were significant clinical risk factors of GBC.The deep learning model achieved the area under the receiver operating characteristic curve(AUC)values of 0.864(95%CI:0.814-0.915)and 0.857(95%CI:0.773-0.942)in the training and validation datasets,which were comparable with radiomics,clinical models and three radiologists.The sensitivity of deep learning model was the highest both in the training[90%(95%CI:82%-96%)]and validation[85%(95%CI:68%-95%)]datasets.Conclusions:The deep learning model may be a useful tool for radiologists to distinguish between GBC and benign gallbladder lesions.

关键词： Gallbladder carcinoma Computed tomography Deep learning Radiomics

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Lightweight foam-like nitrogen-doped carbon nanotube complex achieving highly efficient electromagnetic wave absorption

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Journal of Materials Science & Technology 2024年第1期168卷 114-123页

作者： Zongcheng Li Jin liang Zhiheng Wei Xin Cao Jiahui Shan Chunwei Li Xiaoyi Chen Dong Zhou Ruizhe xing Chunjia Luo jie Kong MOE Key Lab of Materials Physics and Chemistry in Extraordinary Conditions Shaanxi Key Laboratory of Macromolecular Science and TechnologySchool of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Key laboratory of Flexible Electronics of Zhejiang Province Ningbo Institute of Northwestern Polytechnical UniversityNingbo 315103China Polymer Materials and Engineering Department School of Materials Science and EngineeringChang’an UniversityXi’an 710064China

With the increased electromagnetic wave(EMW)threat to military and human health,the develop-ment of EMW-absorbing materials is crucial.Metal-organic framework derivatives containing magnetic nanoparticles and a carbon matrix are potential candidates for designing efficient EMW-absorbing mate-rials.Herein,a zeolitic imidazolate framework-67(ZIF-67)-embedded three-dimensional melamine foam is pyrolyzed to afford carbon foam-based nitrogen-doped carbon nanotube composites,named 3D foam-like CoO/Co/N-CNTs.Magnetic CoO/Co particles are confined in the dielectric carbon nanotube skeleton.The carbon nanotubes provide considerable conductive loss,while CoO/Co magnetic particles are con-ducive to providing magnetic loss and adjusting impedance matching.Moreover,the numerous defect structures introduced by heteroatomic doping(nitrogen)cause dipole polarization and simultaneously adjust impedance matching.Meanwhile,the unique porous nanotube structure promotes multiple re-flections and scattering of EMWs,further optimizing impedance matching.CoO/Co/N-CNTs composites exhibit a minimum reflection loss of−52.3 dB at a matching thickness of 2.0 mm,while the correspond-ing effective absorption bandwidth is 5.28 GHz at a matching thickness of 2.2 mm.This study reports a novel approach to fabricating a lightweight high-performance EMW-absorbing material.

关键词： Lightweight porous carbon materials Carbon nanotubes CoO/Co magnetic particles Electromagnetic synergistic effect Impedance matching

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A micelle-based stage-by-stage impelled system for efficient doxorubicin delivery

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Bioactive Materials 2023年第7期25卷 783-795页

作者： Sunfan Li Fangzhou Li Dong Wan Zuqin Chen jie Pan xing-jie liang School of Chemical Engineering and Technology Tiangong UniversityTianjin300387PR China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaNo.11First North RoadZhongguancunBeijing100190PR China University of Chinese Academy of Sciences Beijing100049PR China Medical School of Chinese PLA No.28 Fuxing RoadBeijing100853PR China Department of Radiology The First Medical CentreChinese PLA General HospitalBeijingPR China Department of Radiology Chinese PAP Guangxi Corps HospitalNanningGuangxiPR China

Chemotherapy remains the mainstay of cancer treatment,benefiting millions of patients each year,but the side effects of chemotherapy drugs severely limit their clinical use.Doxorubicin(DOX)can cause various side effects such as heart damage and treatment-related tumors.The effective use of active and passive targeting will improve the clinical application of DOX.Here,TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system(missiles)for DOX delivery(DOX missiles).By taking advantage of the EPR effect,DOX missiles are efficiently enriched at the tumor site.After being cleaved by matrix metalloproteinase2(MMP2),the peptide(VRGD)targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated endocytosis.The intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor killing.This study provides an efficient approach for DOX delivery and toxicity reduction.

关键词： Doxorubicin Delivery Peptide Missiles Chemotherapy

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Three-dimensional choroidal vascularity index and choroidal thickness in fellow eyes of acute and chronic primary angle-closure using swept-source optical coherence tomography

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 42-52页

作者： Hai-Li Huang Guan-Hong Wang liang-liang Niu xing-Huai Sun Department of Ophthalmology&Visual Science Eye&ENT HospitalShanghai Medical CollegeFudan UniversityShanghai 200031China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceFudan UniversityShanghai 200032China NHC Key Laboratory of Myopia Chinese Academy of Medical Sciencesand Shanghai Key Laboratory of Visual Impairment and Restoration(Fudan University)Shanghai 200031China

AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

关键词： choroidal thickness choroidal vascularity index swept-source optical coherence tomography acute primary angle-closure chronic primary angle-closure glaucoma

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