Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

In the mammalian central nervous system (CNS), astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics. These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological, molecular, and functional changes to adopt so-called 'reactive' states in response to CNS injury or disease. In recent years, interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances. Here, we will review and discuss the well-established and emerging astroglial biology and functions, with emphasis on their potential as therapeutic targets for CNS injury, including traumatic and ischemic injury. This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.
Astrocytes/drug effects* ; Humans ; Animals ; Central Nervous System/pathology* ; Central Nervous System Diseases/physiopathology*

OBJECTIVE: To investigate whether the G protein-coupled estrogen receptor (GPER) can attenuates acute lung injury in mice with exertional heat stroke (EHS) by inhibiting ferroptosis. METHODS: Sixty SPF-grade male C57BL/6 mice were randomly divided into four groups: normal control group (control group), EHS model group (EHS group), dimethyl sulfoxide (DMSO) solvent group (EHS+DMSO group), and GPER-specific agonist G1 group (EHS+G1 group), with 15 mice in each group. All mice underwent 14 days of adaptive training at 24-26 centigrade before modeling, and the EHS model was established using a high-temperature treadmill device. After successful modeling, the mice were allowed to cool naturally at room temperature. In the EHS+G1 group, 40 μg/kg of the GPER-specific agonist G1 was slowly injected intraperitoneally immediately after modeling. In the EHS+DMSO group, 40 μg/kg of DMSO was slowly injected intraperitoneally immediately after modeling. The control group received no treatment. Five hours after modeling, abdominal aortic blood was collected, and lung tissues were harvested after euthanasia. The lung coefficient was calculated to evaluate lung injury. Lung histopathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and a lung histopathological score was assigned. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and Fe²⁺ in lung tissue. Immunofluorescence was used to detect the expression of glutathione peroxidase 4 (GPX4). Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GPX4, ferroportin 1 (FPN1), and ferritin heavy chain 1 (FTH1). Western blotting was performed to detect the protein expression of GPX4, FPN1, and FTH1. RESULTS: Compared with the control group, the lung coefficient and lung histopathological score were significantly increased in the EHS group. HE staining showed significant thickening and unevenness of the alveolar septa and alveolar walls, partial alveolar collapse, and extensive erythrocyte, inflammatory cell, and plasma-like material extravasation in the alveolar spaces. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly elevated. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue. Western blotting and RT-PCR showed significantly reduced protein and mRNA expression of GPX4, FPN1, and FTH1 in lung tissue. Compared with the EHS group, the EHS+G1 group showed a significant reduction in lung coefficient and lung histopathological score [lung coefficient (mg/g): 3.9±0.1 vs. 4.6±0.3, lung histopathological score: 4.2±0.2 vs. 6.9±0.2, both P < 0.05]. HE staining revealed reduced severity of lung tissue fluid extravasation, inflammatory infiltration, decreased hemorrhage, and less severe alveolar structural damage. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly reduced [TNF-α (ng/L): 44.3±0.2 vs. 64.6±0.3, IL-1β (ng/L): 69.3±0.4 vs. 97.8±0.2, MDA (nmol/L): 2.8±0.3 vs. 3.6±0.5, Fe²⁺ (nmol/L): 0.021±0.004 vs. 0.028±0.004, all P < 0.05]. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue (fluorescence intensity: 35.53±2.41 vs. 16.45±0.31, P < 0.05). RT-PCR and Western blotting showed significantly increased mRNA and protein expression of GPX4, FPN1, and FTH1 in lung tissue [mRNA expression: GPX4 mRNA (2^-ΔΔCt): 0.44±0.05 vs. 0.09±0.01, FPN1 mRNA (2^-ΔΔCt): 0.77±0.17 vs. 0.42±0.14, FTH1 mRNA (2^-ΔΔCt): 0.75±0.04 vs. 0.58±0.01; protein expression: GPX4/β-actin: 0.96±0.11 vs. 0.24±0.04, FPN1/β-actin: 1.26±0.21 vs. 0.44±0.14, FTH1/β-actin: 0.27±0.12 vs. 0.15±0.07; all P < 0.05]. However, there were no statistically significant differences in any of the above indicators between the EHS+DMSO group and the EHS group. CONCLUSION Activation of GPER can attenuate EHS-related lung injury in mice, and its mechanism may be related to the activation of the GPX4 signaling pathway and inhibition of ferroptosis.
Animals ; Mice, Inbred C57BL ; Male ; Mice ; Heat Stroke/metabolism* ; Receptors, G-Protein-Coupled ; Ferroptosis ; Receptors, Estrogen ; Acute Lung Injury/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-1beta/metabolism* ; Lung Injury ; Lung/metabolism*

Objective To analyze the working stress related factors of nurses in intensive care unit (ICU), and put forward the corresponding counter measures.Methods During January to March 2016, a questionnaire survey was conducted with a commonly used nurses working pressure source scale on 110 ICU nurses in three People's Liberation Army (PLA) 3A grade hospitals in Beijing. The questionnaire survey involved 35 items within 5 main categories, including nursing professional issues, nursing workload and time allocation, working environment and resources, special care for critical patients and inter-personnel relationships between the head of nurses and other nurses. The correlations between the ICU nursing working stress and alternative factors were analyzed.Results Ninety-six nurses said the job was stressful, and 88.5% of them expressed that the degree of pressure was more than medium. The correlation analysis showed that ICU nurse working stress was correlated with 29 items in the survey scale (allP < 0.05), of which the top 6 items the mostly closely related were the frequent working shift (r = 0.58,P = 0.000), low nursing social status (r = 0.54,P = 0.000), less promotion opportunities (r = 0.54,P = 0.000), less opportunities to pursue further study (r = 0.53, P = 0.000), nurse low salary (r = 0.52,P = 0.000) and excessive workload (r= 0.50,P = 0.000).Conclusions ICU nurses face a lot of pressure in their work, the management departments should pay more attention to them, and actively energetically improve the nurse system construction, raise ICU nurses' pride, enhance the quality of nurse care and promote the healthy development of nursing profession.

Objective To investigate the possible brain diffusion changes in different sites of the brain,particularly in areas associated with vision function,of patients with proliferative and nonproliferative retinopathy by using diffusion-weighted imaging (DWI).Methods Forty-five type 2 diabetic patients,admitted to our hospital from March 2012 to March 2013,were chosen in our study;according to the fundus examination,they were divided into group of proliferative retinopathy (n=15) group of non-proliferative retinopathy (n=15) and group of no retinopathy (n=15); another 15 healthy controls were chosen.T2WI and DWI with 3.0T magnetic resonance imaging (MRI) were performed; the apparent diffusion coefficient (ADC) values in the orbitofrontal cortex,cingulated gyrus,thalamus,dorsomedial and dorsolateral frontal cortex,and corona radiate were calculated; and then,Spearman's correlation analysis was performed between ADC values and both course of disease and glycosylated hemoglobin level.Results The ADC values of orbitofrontal cortex,cingulated gyrus and visual cortex in groups of proliferative and non-proliferative retinopathy were significantly increased as compared with group of no retinopathy and control group (F=95.268,P＜0.05); the ADC values of orbitofrontal cortex,cingulated gyrus and visual cortex in group of proliferative retinopathy were significantly increased as compared with those in group of non-proliferative retinopathy (P=0.004,0.001 and 0.009,respectively);no significant difference of them was noted between group of no retinopathy and control group (P＞0.05).The mean ADC values of orbitofiontal cortex,cingulated gyrus and visual cortex was positively correlated to the duration of disease (r=0.567 and P=0.001; r=0.491 and P=0.01; r=0.428 and P=0.003) and glycosylated hemoglobin level (r=0.336 and P=0.014; r=0.296 and P=0.049; r=0.370 and P=0.012).Conclusion Increased ADC values of visual center (orbitofrontal cortex,cingulated gyrus and visual cortex) conform the association between diabetic retinopathy and brain functioning impairment; DWI may serve to assess subclinical neurogical involvement in diabetic retinopathy,even when brain structural changes are absent.