BACKGROUND: Lead is a persistent inorganic environmental pollutant with global implication for human health. Among the diseases associated with lead exposure, the damage to the central nervous system has received considerable attention. It has been reported that long-term lead exposure increases the risk of meningioma; however, the underlying mechanism remains poorly understood. Clinical studies have indicated that loss-of-function and mutations in the neurofibromin-2 (NF2) gene play a crucial role in promoting meningioma formation. METHODS: The effect of Pb on meningioma were tested in-vitro and in-vivo. Two human meningioma cell lines were used in this study, including NF2-wildtype IOMM-Lee cell and NF2-null CH157-MN cell. Cell viability, cell cycle and cell size were examined after Pb exposure. The expression of Merlin, mammalian sterile 20-like kinases 1 and 2 (MST1/2) and Yes-associated protein (YAP) from these two meningioma cells were analyzed by Western blot. A xenograft mouse model was constructed by subcutaneous injection of IOMM-Lee meningioma cells. RESULTS: This study demonstrated that treatment with lead induce dose-dependent proliferation in IOMM-Lee cell (with an EC₅₀ value of 19.6 µM). Moreover, IOMM-Lee cell exhibited augmented cell size in conjunction with elevated levels of phosphorylated histone H3, indicative of altered cell cycle progression resulting from lead exposure. However, no significant change was observed in the CH157-MN cell. Additionally, the Merlin-Hippo signaling pathway was inactivated with decreased Merlin and phosphorylation levels of MST1/2 and YAP, leading to increased YAP nuclear translocation in IOMM-Lee cells. However, there was no change in the Merlin-Hippo signaling pathway in CH157-MN cells after lead treatment. The administration of Pb resulted in an acceleration of the subcutaneous IOMM-Lee meningioma xenograft growth in mice. CONCLUSIONS Overall, the current study elucidates the potential mechanism by which lead exposure promotes the proliferation of meningioma with NF2 expression for the first time.
Meningioma/genetics* ; Neurofibromin 2/genetics* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Signal Transduction/drug effects* ; Mice ; Hippo Signaling Pathway ; Lead/adverse effects* ; Cell Line, Tumor ; Protein Serine-Threonine Kinases/genetics* ; Meningeal Neoplasms ; Environmental Pollutants/adverse effects* ; Female

OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

OBJECTIVE: To design a portable respiratory device for transporting premature infants and explore its application effect in the in-hospital transportation of extremely premature infants in primary hospitals. METHODS: A prospective randomized controlled trial was conducted. The extremely premature infants born and transferred to neonatal intensive care unit (NICU) with oxygen therapy support from May to October in 2023 were selected and randomly divided into control group and observation group. The infants in the control group received respiratory support and in-hospital transportation using a traditional T-combination resuscitator connected to pure oxygen, and those in the observation group used a portable premature infant transport respiratory device designed and manufactured by medical staff to provide respiratory support and implement in-hospital transportation. The respiratory device for transporting premature infants is made of 304 stainless steel material, mainly consisting of a T-combination resuscitator, an air oxygen mixer, an air tank, a pure oxygen cylinder, a pressure reducing valve, a telescopic rod, a tray, a hook, a bottom plate, and four moving wheels, which can achieve precise control of the fraction of inspired oxygen (FiO₂) during transportation. The achievement rate of first-time target pulse oxygen saturation (SpO₂, achieving a target SpO₂ of 0.90-0.95 was considered as meeting the standard) and arterial partial pressure of oxygen (PaO₂) after being transferred to the NICU, as well as the manpower expenditure and time required for transportation of pediatric patients between the two groups were observed. RESULTS: A total of 73 extremely premature infants were enrolled, including 38 in the control group and 35 in the observation group. There was no significant difference in the gender, gestational age at birth, birth weight, mode of delivery, Apgar score at 1 minute and 5 minutes after birth, and oxygen therapy during the transportation between the two groups. The achievement rate of first-time target SpO₂ after NICU in the observation group was significantly higher than that in the control group [94.29% (33/35) vs. 26.32% (10/38), P < 0.05], the PaO₂ control range was better [mmHg (1 mmHg = 0.133 kPa): 85.50±6.36 vs. 103.00±2.83, P < 0.05], manpower expenditure and time required for transportation were significantly reduced [manpower expenditure (number): 2.14±0.35 vs. 3.17±0.34, time required for transportation (minutes): 10.42±0.76 vs. 15.54±0.34, both P < 0.05]. CONCLUSIONS The portable respiratory device for transporting premature infants is used for respiratory support during the transportation of extremely premature infants in primary hospitals. It can improve the achievement rate of target SpO₂, control PaO₂ within the target range, and avoid hypoxia or hyperoxia during transportation. The breathing apparatus is compact, easy to carry, can save labor resources and time during transport, is cost-effective, and is suitable for widespread application in primary hospitals.
Humans ; Infant, Newborn ; Transportation of Patients ; Prospective Studies ; Equipment Design ; Infant, Extremely Premature ; Intensive Care Units, Neonatal ; Infant, Premature

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

The incidence of myopia among Chinese adolescents is progressively rising, indicating a distinct trend toward younger age onset.This paper aims to comprehensively review the impact of various visual performance on myopia and its progression, with a specific emphasis on accommodative function, convergence function, and ocular position. A meticulous exploration of accommodation function, encompassing accommodative amplitude, accommodative facility, accommodative response, positive relative accommodation, and negative relative accommodation, has been undertaken to elucidate its contributory role in myopia progression. Concurrently, an exhaustive analysis of convergence function has been conducted including esotropia and exotropia, convergence insufficiency and convergence excess, fusional function vergence, divergence insufficiency, and excess, providing a nuanced understanding of convergence's implications for myopia advancement. Furthermore, the influence of ocular position on myopia progression, along with other factors affecting perceptual ocular position and intermittent exotropia, is discussed. The primary objective of this article is to unveil the multifaceted visual performance influencing myopia and its progression, elucidating the paramount significance of accommodative function, convergence function, and ocular position in this context.

AIM:To investigate the application of virtual reality(VR)technology in ocular trauma teaching for medical students.METHODS: A total of 90 medical students who participated in the Ophthalmology teaching program between November 2022 and April 2024 were recruited as subjects. Using a case-control method, 45 students in the case group attended traditional ocular trauma teaching program combined with VR virtual simulation experiments, and 45 students in the control group solely attended traditional ocular trauma teaching program. After the teaching practice, the two groups were compared in terms of their examination performance of theoretical knowledge and case analysis, learning ability(evaluated by the Self-Directed Learning Rating Scale), and the satisfaction survey on the quality of teaching; the statistical analyses were performed using t-test or Chi-square test.RESULTS: The scores of theoretical knowledge and case analysis examinations of the case group were significantly higher than those of the control group, and the differences were statistically significant(scores of theoretical knowledge examination: 57.27±2.78 vs 53.91±3.20; scores of case analysis examination: 35.71±3.73 vs 32.67±5.52, both P<0.05). The scores of the Self-Directed Learning Rating Scale of the case group were significantly higher than those of the control group(P<0.05), and the satisfaction with teaching quality of the case group was significantly higher than that of the control group(P<0.05).CONCLUSION: VR-enabled teaching of ocular trauma can effectively improve medical students' mastery of theoretical knowledge and practical skills, enhance students' self-directed learning ability and improve teaching satisfaction.

ObjectiveKaroshi, death from overwork, is a serious problem with unclear identification standards and mechanisms. This study aims to establish a karoshi rat model by integrating weight-bearing swimming and sleep deprivation. This model will enable us to investigate the adverse effects of acute physical and mental fatigue on cardiac functions and explore the response mechanisms to overwork using integrated omics approaches, specifically metabonomics and proteomics. MethodsThe experimental design involved healthy male sprague-dawley (SD) rats subjected to weight-bearing swimming and sleep deprivation for 7 d. The rats were monitored for changes in physiological function indexes, including electrocardiogram and respiration. Protein digestion, iTRAQ labeling, and quantitative data analyses were performed to determine differentially expressed proteins (DEPs). Additionally, GC-MS analysis was conducted to identify differential metabolites. The integration analysis of differential metabolites and proteins shared by the fatigue group and the overwork group was performed to construct a relevant metabolic pathway network and integrate the proteomics and metabolomics data. Statistical analysis was carried out using one-way ANOVA and Duncan’s multiple range t-tests. ResultsThe rats subjected to weight-bearing swimming and sleep deprivation showed various physical and behavioral changes associated with fatigue, including hair disorder, decreased muscle tension, reduced food intake, and weight loss. Analysis of cardiac functions revealed cardiac hypertrophy and heart failure in the fatigue and karoshi groups, as evidenced by changes in heart color, myocardial fiber structure, heart rate, respiratory rate, and cardiac ultrasound measurements. Metabolomics analysis using GC-MS identified several differential metabolites in response to overwork, including amino acids involved in various metabolic pathways. Proteomic analysis using iTRAQ technology identified DEPs in the fatigue and karoshi groups, with a subset of DEPs shared by both groups. The GO analysis revealed that the up-regulated DEPs were primarily associated with mitochondria and peroxisomes in the cellular component category. The Reactome analysis further highlighted the enrichment of DEPs in the transfer of ferriheme from methemoglobin to hemopexin pathway. Integration analysis of the DEPs and differential metabolites revealed the activation of autophagy, increased mitochondrial oxidative phosphorylation, enhanced branched-chain amino acid degradation, and altered peroxisomal β-oxidation. These findings suggested complex metabolic adaptations to meet the increased energy demands during overwork while also dealing with oxidative stress. Furthermore, the reprogramming of energy metabolism was observed, with upregulation of fatty acid β-oxidation enzymes and glycolysis-related enzymes in the fatigue group, indicating a shift towards glucose metabolism. In contrast, the karoshi group showed a decreased dependence on fatty acids as an energy source and increased utilization of glucose. The model proposed in this study highlights the interconnected metabolic changes involving mitochondria, peroxisomes, and lysosomes in response to overwork. The findings contribute to our understanding of the mechanisms involved in overwork-related pathologies and provide a basis for further research in the field of karoshi. ConclusionOverall, metabolic reprogramming might provide sufficient energy to the heart, alleviate oxidative stress and damage to cardiac cells in response to excessive exertion and fatigue. Our findings provide an insight into response mechanism to overwork death and lay a foundation for further research on overwork death.

Objective To investigate the effect of"zero channel"emergency mode on the treatment of patients with severe traumatic brain injury.Methods A total of 147 patients with severe traumatic brain injury admitted to the Second Hospital of Jiaxing from January 2020 to December 2021 were selected as study objects.Sixty-two patients hospitalized in traditional emergency mode from January to December 2020 were included in control group,and 85 patients hospitalized in"zero channel"emergency mode from January to December 2021 were included in observation group.The initiation time of rescue,completion time of CT examination,completion time of blood transfusion,duration of operation,clinical prognosis and complication rate were compared between two groups.Results The initiation time of rescue,completion time of CT examination,completion time of blood transfusion,and duration of operation in observation group were significantly shorter than those in control group(P<0.05).The proportion of good recovery in observation group was significantly higher than that in control group(68.20%vs.38.70%,χ2=12.671,P<0.001).The complication rate of observation group was significantly lower than that of control group(21.18%vs.80.65%,χ2=51.000,P<0.001).Conclusion"Zero channel"emergency mode can effectively shorten the treatment time of patients with severe traumatic brain injury,improve the success rate of rescue,reduce the incidence of complications,worthy of clinical use and promotion.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.