Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

China is a country with a high incidence of esophageal cancer.The pathological type is mainly squamous cell carcinoma.Squamous intraepithelial neoplasia is the most recognized precancerous lesion of esopha-geal squamous cell carcinoma,and its monitoring and intervention is an effective method to reduce the incidence of esophageal squamous cell carcinoma and improve the quality of life of patients.Understanding the etiology,clinical features,diagnosis and treatment of esophageal squamous cell carcinoma plays a crucial role in the prevention and early diagnosis and treatment of esophageal squamous cell carcinoma.At present,the clinical research related to esophageal squamous intraepithelial neoplasia is still insufficient,and there are some differences in clinical treat-ment.This review summarizes the risk factors,clinical features,diagnosis,prognosis and treatment of esophageal squamous intraepithelial neoplasia,hoping to provide ideas for the clinical management of esophageal squamous intraepithelial neoplasia.

Nephrotic syndrome (NS) has a variety of classifications, pathogenesis and pathological types. Clinical diagnosis primarily relies on serum biochemistry, while the specific classification necessitates renal puncture for biopsy, which is hindered by poor patient compliance. Therefore, it is of great significance for clinical diagnosis to find a non-invasive and rapid method to reflect the classification and progression of nephrotic syndrome. In this study, LC-MS metabolomics combined with receiver operating characteristic (ROC) and multiple linear regression analysis was used to screen and identify potential biomarkers capable of reflecting the typing and progression of nephrotic syndrome. According to the statistical parameters VIP>1, P<0.05 and AUC>0.5 obtained from the orthogonal partial least squares discriminant analysis (OPLS-DA) model, five potential classification markers were screened to distinguish membranous nephropathy (MN) from IgA nephropathy (IgAN), including indoleacetic acid, isoleucine proline, DL-indole-3-lactic acid, D-phenylalanine and L-tryptophan. Furthermore, using estimated glomerular filtration rate (eGFR) as the dependent variable, a multiple linear regression analysis was conducted to identify the potential progression markers capable of reflecting the progression of MN to uremia. These metabolites included alanylleucine, 9-capryloylcarnitine, gluconic acid, caprylyl glycine and sebacic acid. Potential markers of progression of IgA nephropathy to uremia comprised alanylleucine, 9-capryloylcarnitine, caprylyl glycine, and sebacic acid. This study provides a theoretical basis for the discovery of potential classification and progression biomarkers of kidney disease, and also offers a methodological reference for future research in this area. The protocol was approved by the Ethics Committee of Shanxi Provincial People's Hospital [(2020) Provincial Medical Ke Lun Shen Zi No. 30].

Objective:To explore the intervention effects of repetitive transcranial magnetic stimulation on cognitive function of schizophrenia patients with methods using meta-analysis.Methods:CNKI,Wanfang Data,VIP,PubMed,Web of Science,the Cochrane Library and Embase were searched for randomized controlled trials of repetitive transcranial magnetic stimulation on cognitive function in schizophrenia.Quality assessment was per-formed with the Cochrane Handbook for Systematic Reviews.Effect sizes and heterogeneity were assessed using RevMan 5.3.Results:A total of 31 randomized controlled trials(2 421 patients)were included in this study.Meta-analysis showed that rTMS improved cognitive function in schizophrenia patients(SMD=0.73).Subgroup analyses showed that intervention intensity was less than or equal to 100％RMT,the intervention frequency was 1 Hz,the intervention time was lasted at least 20 min/time,and the intervention period was four weeks,the effect of rTMS was better.Subgroup analyses showed that rTMS was more effective in improving for patients with durations of 5 to 10 years.Conclusion:rTMS has more significant improvement effects on cognitive function in schizophrenia pa-tients.It is recommended to set the intervention intensity 100％RMT,the intervention frequency of 1 Hz,the in-tervention time ≥20 min,and the intervention period of 4 weeks in the clinic.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the detection performance of left ventricular ejection fraction (LVEF) in patients with chronic renal failure (CRF) by an artificial intelligence (AI) model based on yolox framework integrating left ventricular segmentation and critical point detection.Methods:From January 2019 to June 2023, a total of 4 284 echocardiographic images of 2 000 adults aged 18-80 years without segmental wall motion abnormalities, structural heart disease, cardiac surgery or cardiomyopathy were collected in Henan Provincial People′s Hospital to delineate the endocardial membrane, as a training set, an AI model based on yolox framework integrating left ventricular segmentation and critical point detection was established. The images were divided into the training set( n=1 675) and the test set( n=325) in a ratio of about 5∶1. All 228 echocardiographic images of 100 normal adult volunteers who were treated in Henan Provincial Chest Hospital from May 2020 to May 2021 were collected as external test set validation. All 792 echocardiographic images of 204 patients treated in Henan Provincial People′s Hospital from April 2019 to June 2023 were continuously enrolled to evaluate the measurement efficiency of AI model. Spearman correlation statistical method was used to analyze the consistency of AI model measurement with manual measurement and TomTec software measurement methods of 3 senior echocardiographic professionals. Subjects were divided into clear image group, unclear image group, normal LVEF group and reduced LVEF group, the differences of general data between the two groups were compared. The correlation coefficient(ICC) within the group was calculated to analyze the consistency, so as to evaluate the model performance. Results:LVEF measured by AI model was significantly correlated with both manual measurement and TomTec model measurement ( rs=0.834, 0.826; all P<0.01). ICC values of the clear image group and the unclear image group were 0.96 and 0.97, respectively. ICC values for all subjects, normal LVEF group and reduced LVEF group were 0.96, 0.90 and 0.96, respectively. Conclusions:The AI model based on yolox framework integrating left ventricular segmentation and critical point detection has good diagnostic performance in the automatic measurement of LVEF in patients with CRF.

Objective:To establish a morphologic classification system for characterizing blast cells in patients with acute promyelocytic leukemia(APL)and analyze the correlation of different APL morphologic characteristics with conventional tests and genetic variants.Methods:Based on the morphological characteristics of APL blast cells,a classification system of 14 categories was established to characterize the inter-and intra-individual cellular morphological heterogeneity of patients.The classification system was used for the morphological analysis of 40 APL patients,and the classification results were statistically analyzed with the patients'conventional test indexes and gene variant characteristics to analyze the correlation of different APL blast cell morphological features with conventional test indexes and gene variants.Results:In the FLT3-ITD mutation-positive group,there were significantly fewer cells with regular nuclear shape,hyper granularity,and missing Auer rods(category 1)than in the FLT3 mutation-negative group(P＜0.05).The activated partial thromboplastin(APTT)was significantly longer in the group with regular nucleus compared to the group with irregular nucleus(P＜0.05).In the hypo-granular group,the APTT was also significantly longer compared to the hyper-granular group(P＜0.01),and the proportion of myeloid blast cells was relatively lower(P＜0.05).The peripheral blood white blood cell counts,D-dimer,lactate dehydrogenase and proportion of bone marrow blast cells were significantly higher in the Auer rods(-)group than Auer rods increasing group(all P＜0.05).Conclusion:The newly established morphologic classification system in this study can objectively characterize different types of APL blast cells,which helps to better assess the intra-and inter-individual heterogeneity of APL blast cells,and further use in accurately analyzing the correlation of morphological phenotypes with biological properties of APL.

Electrochemiluminescence(ECL)refers to the process of luminescence triggered by high-energy electron transfer between intermediate products during the oxidation-reduction reaction on the electrode surface.In the co-reactants involved ECL process,the presence of co-reaction accelerators can effectively catalyze the decomposition of co-reactants,leading to the generation of abundant free radical intermediates,thereby significantly enhancing the ECL signals.This plays a critical role in constructing simple,sensitive,and efficient ECL sensing platforms.This review focused on the novel co-reaction accelerators developed in recent years.Based on different types of co-reaction accelerator materials,including single atom catalysts,metal-based nanomaterials,polymers and other materials,the ECL reaction process and signal enhancement mechanisms,as well as their relevant applications in constructing ECL sensing platforms,were elucidated.Furthermore,the current research challenges and development prospect of co-reaction accelerators were also discussed.