Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

Immunoglobulin A nephropathy （IgAN） is a common primary glomerular disease and a frequent cause of chronic renal failure. Tripterygium wilfordii is a traditional Chinese herbal medicine， which possesses the effects of promoting blood circulation， relieving swelling and pain， and dispelling wind and dampness. Modern pharmacological studies have shown that T. wilfordii multiglucoside exhibit anti-inflammatory and immunomodulatory effects， inhibit mesangial cell proliferation， protect podocytes， ameliorate endothelial cell injury， and regulate gut microbiota disturbances. Triptolide also possesses anti-inflammatory and immunomodulatory properties， suppresses mesangial cell proliferation， and protects podocytes. Celastrol demonstrates anti- inflammatory and immunomodulatory functions as well as the ability to improve endothelial cell damage. Through these mechanisms， T. wilfordii and its active components can play a role in alleviating clinical symptoms and delaying disease progression in the treatment of IgAN. Future research should focus on in-depth analysis and mechanistic investigation of these active ingredients， promote high-quality clinical studies， systematically evaluate the synergistic effects among them， and emphasize strategies for reducing toxicity and enhancing efficacy， thereby providing more comprehensive and reliable evidence-based foundations for the clinical treatment of IgAN.

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

Objective To investigate the effect of oral fish oil on wound healing and related indexes in patients with diabetic foot ulcer(DFU).Methods A randomized,double-blind,placebo-controlled design was used to recruit 68 patients with DFU aged 18-80 years old in the hospital,and the baseline clinical data of the patients were collected.The patients were randomly divided into experimental group(32 cases,fish oil soft capsule,3 g/d)and control group(33 cases,corn oil soft capsule,3 g/d)by random number generated by Ex-cel,and the intervention lasted for 12 weeks.The primary endpoints included the proportion of complete wound healing and healing area≥50%.The secondary endpoints included wound area,healing time,inflamma-tion index,glucose metabolism index,nutrition related index and wound reinfection.Additionally,the influen-cing factors of wound healing were analyzed.Results After intervention,the proportion of complete wound healing and healing area≥50%in the experimental group was significantly higher than that in the control group(P=0.007,0.039).In the subjects with complete wound healing,the mean healing time in the experi-mental group was shorter than that in the control group,but the difference was not statistically significant(P=0.132).The reduction area of wound area in the experimental group was significantly larger than that in the control group(P=0.045).The decrease of interleukin(IL)-6 and IL-8 in the experimental group was significantly higher than that in the control group(P<0.05).There was no significant difference in the reduc-tion of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),neutrophil-to-lymphocyte ratio(NLR),glycated hemoglobin A1c(HbA1c)and platelet-to-lymphocyte ratio(PLR)between the two groups(P>0.05).The improvement of prealbumin(PA)in the experimental group was higher than that in the control group,but the difference was not statistically significant(P>0.05).Multivariate logistic regression analysis showed that oral fish oil intervention(OR=6.771,95%CI:1.787-25.652),HbA1c(OR=4.149,95%CI:1.026-16.770)and ulcer type(OR=4.319,95%CI:1.026-18.173)were the influencing factors of wound healing(P<0.05).Conclusion Oral fish oil promotes wound healing in patients with DFU,which may be re-lated to improving the level of chronic inflammation in the body.

MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.

Background There are a variety of microorganisms in ambient air, and susceptible people can be infected once contact with pathogenic microorganisms in the environment. In order to avoid the spread of pathogenic bacteria, disinfection is the simplest and most effective way of killing pathogenic bacteria in the environment to block the contact between pathogenic bacteria and humans. Sodium hypochlorite (NaClO) is the most widely used disinfectant, but its safety in ambient air disinfection is not clear yet. Objective To establish a model of bronchial epithelial cell (BEAS-2B) injury induced by NaClO, and to explore the mechanism of the toxic effect of NaClO disinfectants on BEAS-2B. Methods Cells were treated with concentration gradients of 0, 25, 50,100, 200, and 400 μmol·L⁻¹ of the diluted NaClO (100 mmol·L⁻¹) standard solution, respectively, and cell activity was measured by cell counting kit-8 (CCK-8) assay after 15 and 30 min. Cells treated with 0, 25, and 50 μmol·L⁻¹ NaClO were selected to observe the cell morphology under an inverted microscope, apoptosis was determined by flow cytometry Annexin V FITC / PI double staining to determine the final experimental concentration. The morphology of organelles such as mitochondria was observed under a transmission electron microscope. Mitochondrial membrane potential of the cells was detected by JC-1 staining. Intracellular Ca²⁺ concentration was measured with a Fluo-4 AM fluorescent probe. Total cellular reactive oxygen species (ROS) was detected with a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe, cell mitochondrial ROS with a dihydroethidium (DHE) fluorescent probe, and lipid peroxidation intermediate malondialdehyde (MDA) with a commercial kit. Results Compared with 0 μmol·L⁻¹, NaClO treatment group, cell morphology did not change a lot after 25 μmol·L⁻¹ NaClO treatment for 30 min, and the cells began to wrinkle and become round after 30 min treatment with 50 μmol·L⁻¹ NaClO, showing about 70% of normal cell viability (P<0.01). So 30 min 50 μmol·L⁻¹ NaClO treatment was selected for the subsequent experiment. The experimental results found that compared with the 0 μmol·L⁻¹ NaClO treatment group, the number of apoptotic cells increased (P<0.05), the mitochondrial membrane potential decreased (P<0.01), the intracellular Ca²⁺ concentration increased (P<0.05), the cellular ROS level increased (P<0.05), the mitochondrial ROS level increased (P<0.01), and the MDA content increased (P<0.01) in the NaClO treatment group.. Conclusion The study has successfully established a model of BEAS-2B injury induced by NaClO, and found that NaClO can lead to cell damage by inducing apoptosis and oxidative stress in BEAS-2B cells. According to the results, there are two possible reasons. First, NaClO solves in water to form hypochlorous acid (HClO) which is oxidative and increases the intracellular ROS level after entering cells, leading to cellular oxidative stress. Second, HClO enters cells to directly attack the mitochondrial membrane, resulting in the imbalance of potential inside and outside the mitochondrial membrane, and apoptosis caused by Ca²⁺ efflux.

BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance