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Macrophages in cardiovascular diseases:molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy 2024年第6期9卷 2598-2641页

作者： Runkai Chen Hongrui Zhang Botao Tang Yukun Luo Yufei Yang Xin Zhong Sifei Chen Xinjie Xu Shengkang Huang Canzhao Liu Department of Cardiology Laboratory of Heart CenterHeart CenterTranslational Medicine Research CenterZhujiang HospitalSouthern Medical University253 Industrial AvenueGuangzhou 510280China State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

The immune response holds a pivotal role in cardiovascular disease *** multifunctional cells of the innate immune system,macrophages play an essential role in initial inflammatory response that occurs following cardiovascular injury,thereby inducing subsequent damage while also facilitating ***,the diverse phenotypes and phenotypic alterations of macrophages strongly associate with distinct types and severity of cardiovascular diseases,including coronary heart disease,valvular disease,myocarditis,cardiomyopathy,heart failure,atherosclerosis and aneurysm,which underscores the importance of investigating macrophage regulatory mechanisms within the context of specific ***,recent strides in single-cell sequencing technologies have revealed macrophage heterogeneity,cell–cell interactions,and downstream mechanisms of therapeutic targets at a higher resolution,which brings new perspectives into macrophage-mediated mechanisms and potential therapeutic targets in cardiovascular ***,myocardial fibrosis,a prevalent characteristic in most cardiac diseases,remains a formidable clinical challenge,necessitating a profound investigation into the impact of macrophages on myocardial fibrosis within the context of cardiac *** this review,we systematically summarize the diverse phenotypic and functional plasticity of macrophages in regulatory mechanisms of cardiovascular diseases and unprecedented insights introduced by singlecell sequencing technologies,with a focus on different causes and characteristics of diseases,especially the relationship between inflammation and fibrosis in cardiac diseases(myocardial infarction,pressure overload,myocarditis,dilated cardiomyopathy,diabetic cardiomyopathy and cardiac aging)and the relationship between inflammation and vascular injury in vascular diseases(atherosclerosis and aneurysm).Finally,we also highlight the preclinical/clinical macrophage targeting strategies and translational

关键词： diseases cardiovascular therapeutic

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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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Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie Department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

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Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

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World Journal of Emergency Medicine 2024年第2期15卷 91-97页

作者： Qing Zhao Jinfu Ma Jianguo Xiao Zhe Feng Hui Liu Department of Diagnosis and Treatment of Cadres the First Medical CenterChinese PLA General HospitalBeijing 100853China Intensive Care Unit the 305th Hospital of Chinese PLABeijing 100032China Department of Critical Care Medicine the First Medical CenterChinese PLA General HospitalBeijing 100853China Nephrology Department the First Medical CenterChinese PLA General HospitalBeijing 100853China

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is *** analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of ***:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)*** identified the co-DEGs and constructed a gene co-expression network to screen the hub *** analyzed immune correlations and disease correlations and performed functional annotation of the hub *** also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription ***,we conducted a correlation analysis to evaluate the role of the hub ***:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney ***,IL32 was significantly associated with mortality in SA-AKI ***,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI ***32 expression increased significantly in the kidney of septic ***-like receptor 2(TLR2)was significantly and negatively correlated with ***:IL32 is the key gene involved in SA-AKI and is significantly associated with ***2 and relevant immune cells are closely related to key genes.

关键词： Sepsis Acute kidney injury Interleukin 32 Toll-like receptor 2 Bioinformatics analysis

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Mapping multiple phases in curcumin binary solid dispersions by fluorescence contrasting

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Chinese Chemical Letters 2024年第9期35卷 266-272页

作者： Ying Xu Chengying Shen Hailong Yuan Wei Wu Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghai 201203China center for medical Research and Innovation Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Department of Pharmacy Air Force Medical CenterPLABeijing 100142China Jiangxi Provincial People’s hospital The First Affiliated Hospital of Nanchang Medical CollegeNanchang 330006China

The microphases and miscibility in binary curcumin(Cur)solid dispersions(SDs)with amorphous polyvinylpyrrolidone K30(PVP K30)and semi-crystalline poloxamer(P407)and poly(ethylene glycol)6000(PEG6000)as carriers were investigated by fluorescence contrasting utilizing confocal laser scanning microscopy.A super sensitive fluorophore P4 with typical aggregation-caused quenching properties was employed to stain the continuous polymer phases and contrasted with the autofluorescence of the model drug *** addition,differential scanning calorimetry(DSC)and powder X-ray diffraction(PXRD)were utilized to assist in explanation of the fluorescence *** all three SD systems,there is always a homogenous polymer phase stained by P4 and it is difficult to adulterate Cur crystals by ***-enriched rather than polymer-enriched domains could be *** the Cur-PVP K30 system,Cur exists in an amorphous form at a Cur loading level of 50%and below,while Cur crystallines phase out and continuously grow with the increase of Cur loading from 60%to 90%.The phase behaviors in the Cur-P407 and Cur-PEG 6000 systems are similar but with minor *** both systems,Cur phases out as clusters of drug-enriched domains at a loading level of 20%and below,which however cannot be correlated with crystallization,as evidenced by both DSC and *** is a transition from an amorphous to a crystalline state from 20%to 30%Cur loading,above which Cur crystallines can be *** is interesting that a co-mix phase of both Cur-and PEG 6000-enriched domains can be identified at Cur loading levels of 10%and *** together,it is concluded that contrasting Cur autofluorescence with the signals of P4 proves to be a functional strategy to reveal multiple phases in the binary SD systems investigated.

关键词： Solid dispersion Curcumin PEG PVP Poloxamer Fluorescence Environment-responsive Confocal laser scanning microscopy

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Cardiovascular Risk Factors in China

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Journal of Geriatric Cardiology 2024年第2期21卷 153-199页

作者： Sheng-Shou HU the Writing Committee of the Report on Cardiovascular Health and Diseases in China Fuwai hospital National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina 不详

The Annual Report on Cardiovascular Health and Diseases in China(2022) intricate landscape of cardiovascular health in China. This section dissects cardiovascular risk factors in China which including hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease, metabolic syndrome and air pollution. Hypertension prevalence has steadily increased in China,with efforts to control it facing challenges in achieving optimal rates, especially in rural areas. Interventions like salt substitutes and intensive blood pressure control show promise but need improvement. Abnormal lipid levels, indicative of dyslipidemia,have risen significantly, posing a risk for cardiovascular diseases. Despite efforts, many patients struggle to achieve target lipid levels, necessitating improved treatment strategies. Both type 1 and type 2 diabetes mellitus affect millions of adults in China,with long-term complications adding to the disease burden. Early intervention and effective management are crucial to mitigate its impact. Prevalent among older adults, chronic kidney disease is associated with diabetes mellitus, hypertension, and cardiovascular diseases, necessitating comprehensive management approaches. The prevalence of metabolic syndrome, characterized by a cluster of risk factors, has increased in both adults and adolescents, calling for lifestyle modifications and public health interventions. Ambient and household air pollution remain significant environmental risk factors, despite some improvements in air quality. Continued efforts to reduce emissions are essential for mitigating associated health risks. Addressing these risk factors requires a multifaceted approach, including public health initiatives, policy interventions, and individual-level strategies to promote healthy lifestyles and reduce environmental exposures. Surveillance and research efforts are crucial for monitoring trends and developing effective strategies to lessen the burden of cardiovascular diseases in

关键词： landscape adding spite

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Bariatric surgery and diabetes:Current challenges and perspectives

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World Journal of Diabetes 2024年第8期15卷 1692-1703页

作者： Yan-Fei He Xiao-Dong Hu Jun-Qiang Liu Hu-Ming Li Shuang-Feng Lu Health Management center The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China Department of Endocrinology The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China Department of Thoracic Surgery The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China Department of Respiratory Medicine The Sixth Medical CenterChinese PLA General HospitalBeijing 100048China

Diabetes mellitus(DM)and obesity have become public issues of global *** surgery for the treatment of obesity combined with type 2 DM has been shown to be a safe and effective approach;however,there are limited studies that have systematically addressed the challenges of surgical treatment of obesity combined with *** this review,we summarize and answer the most pressing questions in the field of surgical treatment of obesity-associated DM.I believe that our insights will be of great help to clinicians in their daily practice.

关键词： Bariatric surgery Diabetes mellitus Obesity Metabolic surgery Challenge

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Therapeutic nucleic acids in regenerative medicine and tissue repair

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Nano Research 2024年第10期17卷 8942-8976页

作者： Qimanguli Saiding Duotian Qin Soohwan An Dylan Neal Patel Muhammad Muzamil Khan Na Kong Wei Tao center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMassachusetts 02115USA

In the vanguard of biomedical innovation,regenerative medicine emerges as a transformative paradigm,concentrating its efforts on rectifying tissue deficits and functional aberrations in patients through the strategic augmentation of endogenous cellular *** to this approach is nucleic acid therapy,which offers a novel pathway for tissue regeneration by modulating key signaling *** one of the most effective ways to regulate cell function,nucleic acids are crucial for various tissue regeneration;however,their in vivo therapeutic applications face substantial challenges,including nuclease degradation,cell membrane impermeability,and targeted intracellular ***-based gene delivery systems offer a solution for stable and localized drug delivery by enabling the controlled overexpression of therapeutic nucleic acids,producing functional regulatory *** review presents examples of nucleic acid applications in regenerative medicine,highlighting the synergy between nucleic acids and biomaterial *** underlines the importance of nucleic acid delivery techniques,the choice of therapeutic nucleic acids,and biomaterials for advancing tissue *** latest developments in designing nucleic acid biomaterial-based delivery vehicles are explored,the mechanism of nucleic acids in tissue regeneration is elucidated,and their limitations are discussed while considering future directions for the clinical translation of nucleic acid-based therapeutics.

关键词： tissue repair nucleic acids biomaterials delivery systems regenerative medicine

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RNF187 governs the maintenance of mouse GC-2 cell development by facilitating histone H3 ubiquitination at K57/80

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Asian Journal of Andrology 2024年第3期26卷 272-281页

作者： Bing-Ya Xu Xiang-Ling Yu Wen-Xin Gao Ting-Ting Gao Hao-Yue Hu Tian-Tian Wu Cong Shen Xiao-Yan Huang Bo Zheng Yi-Bo Wu Human Reproductive and Genetic center Affiliated Hospital of Jiangnan UniversityWuxi 214122China State Key Laboratory of Reproductive Medicine Department of Histology and EmbryologySchool of Basic Medical SciencesNanjing Medical UniversityNanjing 211166China Changzhou Maternal and Child Health Care hospital Changzhou Medical CenterNanjing Medical UniversityChangzhou 213000China State Key Laboratory of Reproductive Medicine Center for Reproduction and GeneticsSuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversitySuzhou 215002China

RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer ***,it remains unclear whether RNF187 exhibits comparable functionality in the development of germline *** investigate thepotential involvement of RNF187 in germ cell development,we conducted interference and overexpression assays using GC-2 cells,a mouse spermatocyte-derived cell *** findings reveal that the interaction between RNF187 and histone H3 increases theviability,proliferation,and migratory capacity of GC-2 ***,we provide evidence demonstrating that RNF187 interactswith H3 and mediates the ubiquitination of H3 at lysine 57(K57)or lysine 80(K80),directly or indirectly resulting in increasedcellular *** is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediatinghistone H3 ubiquitination,thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of *** discoveries provide a new theoretical foundation for further comprehensive investigations into the functionof RNF187 in the reproductive system.

关键词： GC-2 cell histone H3 RNF187 ubiquitination

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Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen College Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse *** its risk factors is crucial to understanding the etiology,prevention,and management of the *** occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(***)infection,and metabolic *** To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,*** infection,and metabolic syndrome on reflux *** Outpatients attending the Second medical center of the PLA General hospital between 2017 and 2021 were retrospectively *** patients’basic information,test results,gastroscopy results,*** test results,and IgG-mediated food intolerance results were *** logistic regression analysis was used to analyze risk factors for reflux *** mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on *** infection affecting reflux *** A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,*** infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,*** analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was *** infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on *** infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on *** infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intol

关键词： Gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori Chemokines

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