Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation and infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, these systems also face several challenges that require resolution, such as difficulties in cell collection and preservation, the need for stability optimization, challenges in large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable precise delivery of anti-cancer drugs to tumor sites, potentially disrupting immunosuppression of the tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, neutrophil-based systems can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems can be achieved by the development of novel nanomaterials and optimization of targeting ligand affinity, thereby improving the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applica-tions, aiming to offer key insights for the development of novel drug delivery systems and advance precision medicine and targeted therapy.
Humans ; Drug Delivery Systems/methods* ; Neutrophils ; Phagocytosis ; Drug Carriers ; Blood-Brain Barrier ; Neoplasms/drug therapy*

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Optimizing operation management mode is the core task to promote the high-quality development of public hospitals.Drawing on the typical experiences and practices of operation and management of representative in-ternational hospitals in the United States,the United Kingdom,Singapore and West China Hospital of Sichuan Univer-sity,Shanghai Jiao Tong University School of Medicine Affiliated Xinhua Hospital,Jilin University China-Japanese Union Hospital of Jilin University,and carrying out a full range of comparative analyses.Put forward the new situation of China's public hospital operations and management to establish a"big operations management"concept.By iden-tifying the operation management role,rationalizing the operation management organization structure and training operation management compound talents to discuss stablishing a committee system,integrating multi-departmental resources to form a scientific and sound problem identificaiton,feedback,consultation and improvement of working mechanism,and promote the high-quality development of publit hospitals.

The access evaluation of new medical technology is an important part of the preclinical application of medical technology and plays a vital role in ensuring the quality and safety of medical services.However,in the con-crete practice of access evaluation,there are still some problems such as imperfect access theoretical framework,imperfect evaluation index system.With the strategic support of health policies,laws,and regulations,the theory and method of HB-HTA are used for reference,core elements such as assessment subject,assessment object,and assessment content are comprehensively considered,the index system is designed from the dimensions of tech-nical characteristics,safety,effectiveness,economy and applicability,and the access evaluation framework of im-ported medical new technologies is constructed.To offer a theoretical framework and evidence-based basis for medi-cal facility medical technology access management.

Objective To measure and comprehensively analyze the operation efficiency of coronary heart disease Center of National Regional Medical Center for Cardiovascular Disease from the dimensions of department service in-come,department service quality,department service efficiency and department service benefit,and put forward targeted operation management optimization strategies based on the analysis results.Methods The operation effective-ness evaluation index of CHD centers in sample hospitals from 2020 to 2022 was measured by the empirical re-search method from the overall level of the center and the level of clinical departments,and the scores were com-pared and analyzed.Results From 2020 to 2022,the operation effectiveness evaluation index of CHD centers in sam-ple hospitals showed a good trend,increasing from 80.57 points to 82.86 points.The 3-year average score was 81.74;Among them,the score rate of department service benefit dimension is higher,the average is 96.64％;The score rate of department service efficiency was lower,with an average of 68.53％.The departments with the lowest operational efficiency scores from 2020 to 2022 are all A2 departments,with 74.39,72.41 and 75.89 scores respec-tively,mainly due to the relatively low scores of A2 departments in the dimensions of department service revenue and department service efficiency.Conclusion The results of clinical department operation effectiveness evaluation can provide the evidence-based basis for hospital operation management,and hospitals can establish benchmarking management departments according to the evaluation results and take targeted measures to improve the comprehen-sive operation efficiency of departments.

Objective To investigate the effects of transcranial direct current stimulation(tDCS)on the topologic attributes of brain functional network in the patients with mild cognitive impairment(MCI).Meth-ods Thirty-three included patients with MCI were randomly divided into the real stimulation group(18 ca-ses)and pseudo-stimulation group(15 cases).All patients received the tDCS treatment for consecutive 10 d.The left dorsolateral prefrontal cortex(DLPFC)was stimulated by the anode,while the right orbital socket DLPFC was stimulated by the cathode.The neuropsychological scale assessment and resting state functional magnetic resonance imaging(rs-fMRI)image collection were performed before and after treatment.The GRETNA software was used to preprocess the rs-fMRI images and analyze the graph theory.The Pearson correlation analysis was used to calculate the correlation between behavioral indicators and network attribute indicators of significant difference between the two groups.Results There were statistically significant differ-ences in the node attributes(intermediate number centrality,degree centrality and local efficiency of nodes)before and after treatment,and between the two groups after treatment(P＜0.05).Compared with before treatment,the scores of MMSE,MoCA,AVLT-N7 and BNT after treatment in the real stimulation group were significantly increased[(25.89±2.16)points,(21.16±2.77)points,(4.95±1.81)points,(19.47±3.13)points].Conclusion tDCS could effectively regulate the local topological attributes of nodes in the cognitive-related brain region of MCI and improve the cognitive function.

Sepsis is one of the leading causes of death in intensive care unit(ICU)patients,typically resulting from excessive inflammation induced by infection,leading to multiple organ dysfunction syndrome and life-threatening complications.Exosomes are a type of extracellular vesicle that are lipid bilayered nanoparticles secreted by cells.In recent years,numerous studies have demonstrated their involvement in the occurrence and development of sepsis.The various molecular substances carried by exosomes have been shown to regulate sepsis-related inflammation and organ damage.In particular,different types of exosomes hold promise as diagnostic biomarkers for sepsis patients,and also provide new therapeutic targets for improving patient outcomes.This review was conducted on the research progress concerning the relationship between exosomes and sepsis,sepsis associated-acute lung injury(SA-ALI),sepsis associated encephalopathy(SAE),sepsis associated-acute kidney injury(SA-AKI),sepsis associated cardiomyopathy(SIC),and other organ injuries related to sepsis.This study aims to assist in guiding clinical diagnosis and treatment.

Objective To explore the relevant protective/risk factors during the development of coronary heart disease blood stasis evidence in the process of pre-existing evidence based on the macro-,meso-,and micro-health state characterization parameter system of Chinese medicine state science.Methods 253 cases of coronary heart disease to be investigated were collected from the outpatient and inpatient departments of the Department of Cardiology in the hospitals affiliated to Hunan University of Traditional Chinese Medicine,and questionnaires were formulated according to the three dimensions of macro,meso,and micro,and the collected parameters were categorized with Python software,and the patients were diagnosed as pre-coronary heart disease blood stasis evidence(150 cases)and coronary heart disease blood stasis evidence(100 cases),and statistical analyses were performed with frequency analysis,χ2 test,and Logistic regression and other methods for statistical analysis.Results ①The results of univariate analysis showed that:age,BMI,history of smoking,history of alcohol consumption,history of hypertension,history of diabetes mellitus,average monthly high temperature,air quality,season,type of occupation,social environment,coronary artery angiographic stenosis,diastolic blood pressure,systolic blood pressure,creatinine,uric acid and total cholesterol differed between patients diagnosed as pre-Coronary artery disease blood stasis evidence and those diagnosed as Coronary artery disease blood stasis evidence,and all the differences were statistically significant(P<0.05).② Binary logistic regression analysis showed that age,BMI,history of alcohol consumption,type of occupation,coronary angiographic stenosis,diastolic blood pressure,creatinine,and dark red tongue were independent risk factors.A prediction model was established:P=1/[1+exp(16.522-1.427×age-0.975×BMI-3.55×drinking history+1.982×monthly average high temperature+0.709×season-1.827×occupational type-1.1×coronary angiographic stenosis-0.072×diastolic blood pressure-0.076×creatinine+2.398×dizziness-4.108×dark red tongue+4.169×pulse asthenia)],the model prediction rate was 90.5%.Conclusion The logistic regression model of coronary heart disease with blood stasis evidence is good with clinical diagnosis,which lays the foundation for the exploration of the state between the already diseased and undiseased of coronary heart disease,and provides important basic data for the theory of subhealth.

Objective:To explore the clinical value of N terminal pro B type natriuretic peptide (NT-proBNP) in diagnosing or predicting heart failure in peridialysis chronic kidney disease (CKD) population.Methods:It was a single-center retrospective study. Patients with peridialysis CKD who visited the Department of Nephrology, First Affiliated Hospital of Zhengzhou University from January 2021 to June 2021 were collected and divided into 4 groups according to the presence or absence of heart failure and the level of left ventricular ejection fraction (LVEF), namely the non-heart failure group, heart failure with reduced ejection fraction (HFrEF) group (LVEF<40%), heart failure with mid-range ejection fraction (HFmrEF) group (40％≤LVEF<50％), and heart failure with preserved ejection fraction (HFpEF) group (LVEF≥50％). The NT-proBNP, echocardiography and other indicators of the 4 groups were compared. The value of plasma NT-proBNP in diagnosing heart failure, HFpEF, HFmrEF and HFrEF was analyzed by drawing receiver operating characteristic curve (ROC curve). Logistic regression analysis was used to analyze the related factors of heart failure in peridialysis CKD patients.Results:A total of 508 patients were included, including 11 cases in the HFrEF group, 29 cases in the HFmrEF group, 152 cases in the HFpEF group, and 316 cases without heart failure. The differences in age, 24-h urine volume, hemodialysis proportion, non-dialysis proportion, serum creatinine, estimated glomerular filtration rate, hemoglobin, serum albumin, C-reactive protein, NT-proBNP, cardiac troponin I, left ventricular internal diameter, LVEF, pulmonary artery systolic pressure, left ventricular end-diastolic volume, E/A value, septal thickness, and left ventricular posterior wall thickness among the four groups were statistically significant ( P < 0.05, respectively). A two-pair comparison (all P values corrected by Bonferroni method) revealed that the 24-h urine volume was higher in the non-heart failure group than in the other three groups (corrected P<0.05, respectively), while the proportion of hemodialysis patients and the levels of NT-proBNP and C-reactive protein were lower in the non-heart failure group than in the other three groups (corrected P<0.001, respectively); the levels of hemoglobin and serum albumin were lower in the HFpEF group than in the non-heart failure group (corrected P<0.001, respectively); troponin I was lower in the non-heart failure group than in the HFpEF group (corrected P<0.001), HFmrEF group (corrected P=0.001) and HFrEF group (corrected P<0.001), and troponin I was lower in the HFpEF group than in the HFrEF group (corrected P=0.008); LVEF was higher in the non-heart failure group than in the other three groups (corrected P<0.001, respectively), and LVEF in the HFpEF group was higher than in the HFmrEF and HFrEF groups (corrected P<0.001, respectively). For patients with peridialysis CKD, the cut-off values of plasma NT-proBNP for diagnosing or predicting heart failure, HFpEF, HFmrEF and HFrEF were 4 943.33 ng/L, 4 976.83 ng/L, 14 964.5 ng/L and 17 847.55 ng/L, respectively. Multivariate logistic regression analysis showed that NT-proBNP (every 500 ng/L increase, OR=1.390, 95% CI 1.287-1.501, P<0.001), LVEF ( OR=0.747, 95% CI 0.656-0.851, P<0.001) and 24-h urine volume (every 100 ml increase, OR=0.842, 95% CI 0.763-0.929, P=0.001) were independently correlated with heart failure. Conclusions:The cut-off value of plasma NT-proBNP for diagnosing or predicting heart failure in peridialysis CKD patients is much higher than that in patients with normal renal function. NT-proBNP, LVEF and 24-h urine volume are independently associated with heart failure in peridialysis CKD patients.

In acute lung injury, two subsets of lung macrophages exist in the alveoli: tissue-resident alveolar macrophages (AMs) and monocyte-derived alveolar macrophages (MDMs).However, it is unclear whether these 2 subsets of macrophages have different functions and characteristics during the recovery phase. RNA-sequencing of AMs and MDMs from the recovery period of LPS-induced lung injury mice revealed their differences in proliferation, cell death, phagocytosis, inflammation and tissue repair. Using flow cytometry, we found that AMs showed a higher ability to proliferate, whereas MDMs expressed a larger amount of cell death. We also compared the ability of phagocytosing apoptotic cells and activating adaptive immunity and found that AMs have a stronger ability to phagocytose, while MDMs are the cells that activate lymphocytes during the resolving phase. By testing surface markers, we found that MDMs were more prone to the M1 phenotype, but expressed a higher level of pro-repairing genes. Finally, analysis of a publicly available set of single-cell RNA-sequencing data on bronchoalveolar lavage cells from patients with SARS-CoV-2 infection validated the double-sided role of MDMs. Blockade of inflammatory MDM recruitment using CCR2 −/− mice effectively attenuates lung injury. Therefore, AMs and MDMs exhibited large differences during recovery. AMs are long-lived M2-like tissue-resident macrophages that have a strong ability to proliferate and phagocytose. MDMs are a paradoxical group of macrophages that promote the repair of tissue damage despite being strongly pro-inflammatory early in infection, and they may undergo cell death as inflammation fades. Preventing the massive recruitment of inflammatory MDMs or promoting their transition to pro-repairing phenotype may be a new direction for the treatment of acute lung injury.