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.

Objective: To investigate the influencing factors for cognitive function among aluminum workers, so as to provide the basis for intervention and prevention of cognitive function among aluminum-exposed populations. Methods: From July to August 2019, male aluminum workers in the electrolytic aluminum workshop of an aluminum factory in Shanxi Province were selected using the cluster sampling method. Demographic information, prevalence of chronic diseases, lifestyle behaviors, night shifts, and sleep quality were collected through questionnaire surveys. Blood aluminum levels were measured using inductively coupled plasma-mass spectrometry. Cognitive function was investigated using the Montreal Cognitive Assessment. Factors affecting cognitive function among aluminum workers were analyzed by a quantile regression model. Results: A total of 142 aluminum workers were surveyed, including 57 workers aged 20 to <40 years (40.14%) and 85 workers aged 40 to 60 years (59.86%). The median blood aluminum level was 38.23 (interquartile range, 21.82) μg/L. The median cognitive function score was 24.00 (interquartile range, 3.00) points. Quantile regression analysis revealed that older age (βQ5=-0.186, 95%CI: -0.269 to -0.102), lower educational level (βQ5=1.933, 95%CI: 1.029 to 2.838; βQ10=1.743, 95%CI: 0.480 to 3.006; βQ50=1.038, 95%CI: 0.141 to 1.935; βQ75=1.006, 95%CI: 0.437 to 1.575; βQ90=1.111, 95%CI: 0.291 to 1.930), smoking (βQ5=-2.056, 95%CI: -3.264 to -0.849), alcohol consumption (βQ5=-1.821, 95%CI: -3.247 to -0.396) and higher blood aluminum level (βQ5=-0.075, 95%CI: -0.110 to -0.040; βQ10=-0.078, 95%CI: -0.127 to -0.029; βQ50=-0.075, 95%CI: -0.110 to -0.040; βQ75=-0.057, 95%CI: -0.079 to -0.035; βQ90=-0.067, 95%CI: -0.099 to -0.035) were associated with cognitive function decline among aluminum workers. Conclusions Educational level and blood aluminum level are the main factors affecting the cognitive function among aluminum workers. Among those with lower cognitive function scores, age, smoking and alcohol consumption are also associated with cognitive function.

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Background Some studies have suggested that exposure to multiple metals is closely linked to the development of metabolic syndrome (MS) in the populations, but the effect of aluminum exposure on MS remains unclear. Objective To analyze the prevalence and influencing factors of MS among employees with aluminum exposure in Shanxi Province. Methods Cluster sampling was employed to survey male frontline workers in an aluminum factory in Shanxi Province. Data on general demographic information, lifestyle, occupational history, medical history, and family history of chronic diseases were collected through questionnaires. The concentration of fasting blood glucose was determined using the glucose oxidase technique, and blood lipid levels were determined using the peroxidase method. Serum aluminum levels were detected using inductively coupled plasma-mass spectrometry (ICP-MS), and blood biochemical indicators were measured using the peroxidase method. Based on the China's 2020 diagnostic criteria for MS, the participants were and divided into an MS group anda non-MS group. Variables with statistical significance in univariate analysis were included to construct a logistic regression model. Results A cohort of 312 workers participated in this research, with 84 individuals diagnosed with MS, yielding a prevalence rate of 26.92%. The logistic regression model revealed that body mass index (BMI)≥24.0 kg·m⁻² (OR=1.967, 95%CI: 1.057, 3.659), alcohol consumption (OR=1.883, 95%CI: 1.063, 3.336), experiencing major life event (OR=3.886, 95%CI: 1.509, 10.008), family history of hypertension (OR=2.112, 95%CI: 1.162, 3.837), serum aluminum concentration (OR=1.024, 95%CI: 1.012, 1.035), alanine aminotransferase (ALT) level (OR=1.032, 95%CI: 1.011, 1.054), and white blood cell (WBC) count (OR=1.210, 95%CI: 1.001, 1.465) were significant influencing factors for MS. Conclusion BMI≥24.0 kg·m⁻², alcohol consumption, experiencing major life event, family history of hypertension, elevated serum aluminum concentration, increased ALT level, and elevated WBC count are risk factors for MS among occupationally aluminum-exposed workers.

Background Quartz dust cannot be degraded in the lungs, and inhalation of a large amount of quartz dust in the occupational production process will lead to the occurrence of pulmonary fibrosis, and then develop into silicosis. In recent years, studies have found that exosomes may be involved in the pathogenesis of fibrotic diseases by carrying microribonucleic acid (miRNA), but the mechanism of their actions in silicosis still needs to be studied. Objective To investigate the role of exosome-derived miRNA-21-5p/mothers against decapentaplegic homolog 7 (Smad7) in quartz dust-induced pulmonary fibrosis in rats. Methods Twenty-four healthy male SD rats were randomly divided into four groups (six rats in each group): control 4-week group, control 16-week group, quartz 4-week group, and quartz 16-week group. At the beginning of the experiment, 1 mL of quartz suspension (50 mg·mL⁻¹) and 1 mL of normal saline were injected into the trachea of rats in the quartz group and the control group, respectively, by means of one-time non-exposure intratracheal dust staining. Alveolar lavage was performed at the 4th and 16th weeks after dust staining, the exosomes in lavage solution were extracted by polyethylene glycol (PEG) precipitation, morphological identification was conducted by transmission electron microscopy (TEM), particle size of exosomes was detected by nano-tracking analysis (NTA), and the marker proteins CD9 and CD63 of exosomes were detected by Western blotting (WB). The expression of miRNA-21-5p in exosomes was determined by reverse transcription polymerase chain reaction (RT-PCR). The degree of lung tissue injury and fibrosis was observed by hematoxylin-eosin staining (HE) and Masson staining. The collagen content of lung tissue was detected by hydroxyproline (HYP) method. The expression of Smad7 protein in lung tissue was detected by WB. Results The results of pathological staining showed that compared with the control group, lung inflammatory cell infiltration, alveolar wall thickening, and collagen increase were observed after 4 weeks of dusting, and collagen deposition and silicon nodules appeared after 16 weeks of dusting. Compared with the control group, the expression level of HYP in the lung tissue of the quartz group was increased after 4 weeks and 16 weeks of dust staining (P<0.05). Transmission electron microscopy showed that exosomes were saucer-shaped, and the average particle size of exosomes was 95.8 nm by NTA. Positive expression of exosome marker proteins CD9 and CD81 was found by WB. Compared with the control group, the expression of exosome-derived miRNA-21-5p in alveolar lavage fluid in the quartz group increased in the 4th week and the 16th week (P<0.05), and the expression of Smad7 protein in lung tissue decreased (P<0.05). Conclusion Exosome-derived miRNA-21-5p and Smad7 may be involved in the mechanism of quartz dust-induced pulmonary fibrosis in rats.

Objective: To explore the effects of subchronic aluminum exposure on the level of N6-methyladenosine (m6A) methylation and the expression of N6-methyladenosine RNA binding protein 1 (YTHDF1) in the hippocampus of rats. Methods: Twenty-four healthy male SD rats were randomly divided into the control group (normal saline), the low dose group [10 μmol/kg Al(mal)3], the medium dose group [20 μmol/kg Al(mal)3] and the high dose group [40 μmol/kg Al(mal)3], with 6 rats in each group. The Al(mal)3 solution was administered via intraperitoneal injection on alternate days for 90 days. Escape latency, target quadrant dwell time and platform crossing times were tested to evaluate the learning and memory ability of the rats by the Morris water maze test after exposure. The brain tissue was weighted and the brain-to-body weight ratio was calculated after euthanasia. The level of m6A methylation and the expression of YTHDF1 were determined by enzyme-linked immunosorbent assay and western blot assay, respectively. Results: All rats survived during aluminum exposure period. The brain-to-body weight ratios of the control group and the low, medium and high dose groups were (0.46±0.06)%, (0.44±0.04)%, (0.49±0.06)% and (0.51±0.07)%, respectively, with no statistically significant differences (P>0.05). The escape latency of rats in the high dose group was longer than that in control and low group during the third to fifth day (both P>0.05). The escape latency of rats in all groups was shortened with the increase of training days (P<0.05). The target quadrant dwell time of rats in low, medium and high dose groups were lower than that in control group, and the platform crossing times of rats in high dose group were lower than that in control group (all P<0.05). The methylation level of m6A and expression level of YTHDF1 in hippocampus of rats in medium and high dose groups was higher than that in control group (both P<0.05). Conclusion The learning and memory impairment caused by subchronic aluminum exposure may be related to the increase of m6A methylation level and the decrease of YTHDF1 expression.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

Objective: To investigate the changes in the levels of interleukin-6 (IL-6) and let-7e in rats induced by coal mine dust, so as to provide the basis for the mechanism of coal worker's pneumoconiosis (CWP). Methods: Sixty-four clean and healthy male Sprague-Dawley rats were randomly divided into the control group, coal dust group, mixed dust group (mixed coal and silica dust) and quartz group. The rats in the control group were exposed to 1 mL physiological saline by non-exposure tracheal perfusion, and the rats in the dust-exposed groups were exposed to 1 mL dust suspension. Rats were sacrificed by anesthesia after 1 month and 6 months, lung tissue was observed using hematoxylin-eosin staining, the pathological change in the lungs was scored using the Szapiel scoring system, the levels of IL-6 in the bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay, and the expression of let-7e was determined by quantitative real-time PCR. Results: A month after exposure, a small amount of coal spots and inflammatory exudation were observed in the lung tissue of the coal dust group and the mixed dust group. The quartz group showed tissue structure destruction and mild fibrosis and thickening of alveolar septum. Six months after exposure, there were more coal spots and slightly thickened alveolar septum in the coal dust group, and hyperplasia of pulmonary interstitial fibers, destruction of alveolar structure and silica nodules were observed in the mixed dust group. In the quartz group, the alveolar structure was obviously destroyed, the interstitial fiber proliferation was significant and silica nodules were seen. Two-factor analysis of variance showed that the interaction between duration of exposure and dust type significantly influenced the pathological score of lung tissue, IL-6 levels, and let-7e expression levels (P<0.05). Under the same dust type, the pathological score of lung tissue and IL-6 levels were higher at 6 months after exposure than at 1 month, while the relative expression of let-7e was lower at 6 months after exposure than at 1 month (all P<0.05). Under the same duration of exposure, the pathological score of lung tissue and IL-6 levels were higher in the dust-exposed groups than in the control group, while the relative expression of let-7e was lower in the dust-exposed groups than in the control group (all P<0.05). Conclusions Coal dust can cause an increase in levels of IL-6 and a decrease in let-7e expression in rats. The type of dust and duration of exposure can interactively affect IL-6 and let-7e.