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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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Mitochondrial Regulation of Macrophages in Innate Immunity and Diverse Roles of Macrophages During Cochlear Inflammation

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Neuroscience Bulletin 2024年第2期40卷 255-267页

作者： Yuan Zhang Fanglei Ye Xiaolong Fu Shen Li Le Wang Yutian Chen Hongmin Li Shaojuan Hao Kun Zhao Qi Feng Peipei Li Department of Otology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Shandong Provincial hospital Shandong First Medical UniversityJinan 250000China Department of Neurology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China The Department of Endovascular Surgery The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Integrated Traditional and Western Nephrology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Province Research Center of Kidney Disease Zhengzhou 450052China

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and *** regulate macrophage activation and innate immune responses in various inflammatory diseases,including cochlear *** distribution,number,and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions,including noise exposure,ototoxicity,and age-related ***,the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains ***,we summarize the major factors and mitochondrial signaling pathways(e.g.,metabolism,mitochondrial reactive oxygen species,mitochondrial DNA,and the inflammasome)that influence macrophage activation in the innate immune *** particular,we focus on the properties of cochlear macrophages,activated signaling pathways,and the secretion of inflammatory cytokines after acoustic *** hope this review will provide new perspectives and a basis for future research on cochlear inflammation.

关键词： Macrophage Mitochondria Innate immunity Cochlea Infammation

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New pimarane diterpenoids with antibacterial activity from fungus Arthrinium ***03

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Chinese Journal of Natural Medicines 2024年第4期22卷 356-364页

作者： ZHAO Songfeng JING Ziwei Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

A comprehensive chemical study of the endophytic fungus Arthrinium sp. ZS03, associated with Acorus tatarinowii Schott, yielded eleven pimarane diterpenoids (compounds 1–11), including seven novel compounds designated arthrinoids A–G (1–7). The determination of their structures and absolute configurations was achieved through extensive spectroscopic techniques, quantum chemical calculations of electronic circular dichroism (ECD), and single-crystal X-ray diffraction analysis. Furthermore, 7 demonstrated inhibitory activity against Klebsiella pneumoniae, comparable to the reference antibiotic amikacin, with a minimum inhibitory concentration (MIC) of 8 μg·mL^(−1).

关键词： Arthrinium sp.ZS03 Pimarane diterpenoids Structural elucidation Antibacterial activity

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Effects of extracellular vesicle-derived noncoding RNAs on pre-metastatic niche and tumor progression

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Genes & Diseases 2024年第1期11卷 176-188页

作者： Zhuang Chen Qiming Wang Jinbo Liu Wenkang Wang Weitang Yuan Yang Liu Zhenqiang Sun Chengzeng Wang Department of Colorectal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Academy of Medical Sciences of zhengzhou university ZhengzhouHenan 450001China Department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenan 450008China Department of Breast Surgery The First Affliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Radiotherapy Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenan 450008China The first Affiliated hospital of zhengzhou university ZhengzhouHenan 450052China

A pre-metastatic niche(PMN)is a protective microenvironment that facilitates the colonization of disseminating tumor cells in future metastatic *** vesicles(EVs)play a role in intercellular communication by delivering cargoes,such as noncoding RNAs(ncRNAs).The pivotal role of extracellular vesicle-derived noncoding RNAs(EV-ncRNAs)in the PMN has attracted increasing *** this review,we summarized the effects of EV-ncRNAs on the PMN in terms of immunosuppression,vascular permeability and angiogenesis,inflammation,metabolic reprogramming,and fibroblast *** particular,we provided a comprehensive overview of the effects of EV-ncRNAs on the PMN in different ***,we discussed the promising clinical applications of EV-ncRNAs,including their potential as diagnostic and prognostic markers and therapeutic targets.

关键词： Biomarker Extracellular vesicles Noncoding RNAs

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Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 293-299页

作者： Rong-Tao Zhu Ye Li Chi-Xian Zhang Wei-Jie Wang Ruo-Peng Liang Jian Li Kai Bai Yu-Ling Sun Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China zhengzhou Key Laboratory of Hepatobiliary and Pancreatic Diseases Zhengzhou 450052China Institute of Hepatobiliary and Pancreatic Diseases Zhengzhou UniversityZhengzhou 450052China Department of Pathology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well *** explore this subtype of acute cholangitis,we described our clinical experience with ***:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August *** analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and ***:A total of 32 ASTC patients were included in the *** majority of the patients had a history of biliary operations,and clinical manifestations were occult and *** positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance *** with effective antibiotics was provided as soon as diagnosis was *** treatment,most patients had a good *** levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor ***:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.

关键词： Acute suppurative terminal cholangitis Acute cholangitis Gram-negative bacterial infections Diagnosis Treatment

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Sonodynamic therapy for the treatment of atherosclerosis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 666-677页

作者： Yan Zhang Ying Yang Yudi Feng Xueyan Gao Liping Pei Xiaopan Li Bingxin Gao Lin Liu Chengzeng Wang Shuochen Gao The Department of Ultrasound The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China The Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular *** the current treatments,mortality and disability still remain *** therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing *** progress has been made through cell and animal assays,as well as clinical *** example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been *** this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

关键词： Atherosclerosis Sonodynamic therapy Sonosensitizer Ultrasound Reactive oxygen species

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Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

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Chinese Journal of Integrative Medicine 2024年第6期30卷 559-564页

作者： ZHANG Rong-rong SHAO Ming-yi FU Yu ZHAO Rui-xia WANG Jing-wen FANG Yu-xuan The first Clinical Medical College of Henan university of Traditional Chinese Medicine Zhengzhou450046China Personal Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Scientific Research Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Digestive Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical *** controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation *** total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, *** on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

关键词： multi-criteria decision analysis benefit-risk assessment Chinese medicine injections primary livercancer

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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： Xudong Li Wei Li Yanli Zhang Linping Xu Yongping Song Department of Hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

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Real-time shear wave elastography combined with biochemical indicators for evaluating liver injury in patients with chronic kidney disease

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中国医学影像技术 2024年第8期40卷 1221-1225页

作者： FAN Xiangyang ZHANG Yan HE Xiao WANG Ziwei YU Jing Department of Ultrasound the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Objective To observe the value of real-time shear wave elastography(SWE)combined with biochemical indicators for evaluating liver injury in patients with chronic kidney disease(CKD).Methods Totally 210 patients with CKD(CKD group)and 64 healthy subjects(control group)were retrospectively *** in CKD group were further divided into CKD1—5 subgroups according to CKD *** parameters of liver and kidney,including mean value,the maximum value and the median value of Young's modulus(EQI mean,EQI max and EQI med)were compared between CKD subgroups and control *** correlation analysis were performed to explore the correlations of liver and kidney SWE parameters with CKD stage,as well as of liver SWE parameters with biochemical *** logistic regression analysis was used to screen independent predictors of liver injury in CKD *** operating characteristic curves were drawn,the area under the curves(AUC)were calculated to evaluate the efficacy of the independent predictors alone and their combination for assessing liver injury in CKD *** Significant differences of liver and kidney SWE parameters were found among CKD subgroups and control group(all P≤0.001).Pairwise comparison showed that liver SWE parameters in CKD5 subgroup and liver EQI max in CKD4 subgroup were all higher than those in control group(all P<0.003).Kidney SWE parameters in CKD3 subgroup were all higher than those in control group,while in CKD4 subgroup were all higher than those in control group and CKD1—3 subgroup(all P<0.003).Kidney EQI mean and EQI med in CKD5 subgroup were all higher than those in control group and CKD1—4 subgroup,while kidney EQI max in CKD5 subgroup were higher than those in control group and CKD1—3 subgroup(all P<0.003).Liver and kidney SWE parameters were lowly-moderately and positively correlated with CKD stages(r=0.364—0.665,all P<0.001).Liver SWE parameters of CKD were weakly and positively correlated with al

关键词： renal insufficiency,chronic hepatic insufficiency ultrasonography

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Chimeric antigen receptor-immune cells against solid tumors:Structures,mechanisms,recent advances,and future developments

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Chinese Medical Journal 2024年第11期137卷 1285-1302页

作者： Xudong Li Wei Li Linping Xu Yongping Song Department of Hematology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China

The advent of chimeric antigen receptor(CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological ***,their success in treating solid tumors has been ***-natural killer(NK)cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex(MHC),which means they are more likely to become an"off-the-shelf"***,they can kill cancer cells via CAR-dependent/independent pathways and have limited *** are the most malleable immune cells in the *** cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments(TMEs).Importantly,CAR-macrophages(CAR-Ms)have recently yielded exciting preclinical results in several solid ***,CAR-T,CAR-NK,and CAR-M all have their own advantages and *** this review,we systematically discuss the current status,progress,and the major hurdles of CAR-T cells,CAR-NK cells,and CAR-M as they relate to five aspects:CAR structure,therapeutic mechanisms,the latest research progress,current challenges and solutions,and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.

关键词： Immunotherapy Chimeric antigen receptor-T cells Chimeric antigen receptor-NK cells Chimeric antigen receptor-macrophage Solid tumors

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