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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

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

The role of intestinal flora on tumorigenesis,progression,and the efficacy of PD-1/PD-L1 antibodies in colorectal cancer

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Cancer Biology & Medicine 2024年第1期21卷 65-82页

作者： Sen Wang Benling Xu Yangyang Zhang Guangyu Chen Peng Zhao Quanli Gao Long Yuan Department of Gastrointestinal Surgery Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China Department of Immunotherapy Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China

Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR *** recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC *** and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in ***,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 *** addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

关键词： Intestinal flora anti-PD-1/PD-L1 therapy colorectal cancer immune checkpoint inhibitor CD8~+T cell

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

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

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

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

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

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

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World Journal of Emergency Medicine 2024年第4期15卷 263-272页

作者： Yuhan Sun Baoqing Sun Zhigang Ren Mingshan Xue Changju Zhu Qi Liu Translational Medicine Center Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Infectious Disease the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Medical Key Laboratory of Emergency and Trauma Research Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality *** aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and ***:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April *** were allocated to the DM or non-DM group and paired with propensity score *** characteristics and clinical outcomes up to 90 days were *** primary outcome was the 10-day *** operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical ***:Among 152 enrolled patients,60 pairs were successfully *** was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml *** 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of *** cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,*** Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with ***:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.

关键词： Community-acquired pneumonia Diabetes mellitus Heparin-binding protein Propensity score match