Objective To investigate the protective effects of ferroptosis inhibitor ferrostatin-1(Fer-1)on high-altitude hypoxic lung injury and explore novel preventive strategies for high-altitude hypoxia-induced lung injury.Methods ①Eighteen SPF male Wistar rats(5～6 weeks old,210～230 g)were randomly divided into 3 groups(n=6):normoxic control,hypoxic lung injury,and Fer-1 pretreatment groups.A hypobaric chamber was used to establish a rat model of high-altitude hypoxic lung injury.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was employed to compare pulmonary protein profiles between normoxic and hypoxic groups,followed by bioinformatics analysis of pathways enriched with differentially expressed proteins(DEPs).Histopathological changes and lung injury scores were assessed with HE staining.ELISA was used to quantify the inflammatory cytokines,flow cytometry and immunofluorescence assay were employed to measure the production of reactive oxygen species(ROS),and spectrophotometry was utilized to determine the contents of Fe2?,glutathione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)to evaluate oxidative stress and detect ferroptosis-related markers.② Human bronchial epithelial cells(bronchial epithelium transformed with Ad12-SV40,BEAS-2B)and macrophages induced by tumor human peripheral blood monocytes-1(THP-1)cells were placed in a low oxygen conditions for 48 h to establish a cellular model of hypoxic lung injury,on which Fer-1 was administered as a preventive group.Ferroptosis markers in BEAS-2B cells and inflammatory cytokine secretion in macrophages were analyzed.Results ①Proteomics identified 2 962 proteins,with 357 DEPs(199 up-regulated,158 down-regulated).Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed ferroptosis as the most enriched pathway.Hypoxic lung injury resulted in elevated ROS,MDA,Fe2?,and inflammatory cytokines(P<0.05),reduced SOD,GSH,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy chain 1(FTH1),and increased acyl-coa synthetase long chain family member 4(ACSL4)(P<0.05).Fer-1 pretreatment significantly mitigated oxidative stress(ROS,MDA,SOD,GSH;P<0.05),up-regulated SLC7A11 and FTH1,down-regulated ACSL4(P<0.05),and reduced inflammation(P<0.05).②In cellular models,Fer-1 increased SLC7A11,GPX4,FTH1,GSH,and SOD(P<0.05),declined ROS(P<0.05),and suppressed macrophage inflammatory cytokines(P<0.05).Conclusion Fer-1 alleviates high-altitude hypoxic lung injury by inhibiting ferroptosis in pulmonary epithelial cells and attenuating macrophage-driven inflammation,providing experimental evidence for novel therapeutic strategies.

The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

Quality marker (Q-Marker) is an innovative concept and model for quality control of Traditional Chinese medicines (TCMs), which will navigate the new direction of quality development of TCMs. Yet, how to characterize the overall quality attributes of TCMs and their biological effects is still debating. In view of this key scientific issue, this paper proposes a research method based on mass spectrometry imaging (MSI) technology for the discovery and confirmation of TCMs Q-Marker. MSI is powerful in investigating the spatial distribution of molecules in a variety of samples, and visualizing the information obtained from MS. On this basis, combine with the five principles of TCMs Q-Marker validation, i.e., specificity, transmission and traceability, testability, prescription compatibility, and validity, were applied to confirm the finalized Q-Marker. It will lead the new direction of quality development of TCMs.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective:To retrieve, evaluate, and integrate evidence on the humanistic care practice of physical restraints for adult patients in the ICU to inform the management of physical restraints for clinical ICU patients.Methods:Expert consensus, group standards, systematic reviews, clinical decisions, best practices, guidelines, evidence summaries, and other types of literature related to the humanistic care of physical restraints for adult patients in the ICU were electronically searched in Chinese and English databases, relevant association websites, and guideline websites. The search period was from database establishment to August 31, 2024. Evidence was extracted and summarized according to themes after an independent literature quality assessment by two researchers.Results:A total of 15 articles were included, including four guidelines, one group standard, three best practices, five systematic reviews, and two expert consensus. Literature reading, evidence extraction and categorization resulted in seven themes of 39 best evidence on respecting patients' personality and dignity, attending to patients' physical needs, attending to patients' psychological needs, attending to patients' social and cultural needs, establishing good communication and trusting relationships, attending to patients' family and social support, and providing comprehensive nursing services.Conclusions:The best evidence summarized in this study may provide an evidence-based basis for the proper use of physical restraints by ICU medical and nursing staff to ensure patient safety and improve the ICU patient experience.

Objective In this study,we investigated the correlation between the scores for different Liebowitz Social Anxiety Scale(LSAS)subscale models and the metabolic activity in specific regions of the brain using 18F-fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT)(18F-FDG PET),thereby improving the understanding of the neurobiological characteristics of social anxiety.Methods A total of 39 cognitively normal participants(29 men and 10 women,aged 30-63 years)were enrolled.All participants underwent LSAS assessment and brain 18F-FDG PET scanning.Correlations between metabolic activities in various brain regions and scores from the different LSAS subscales were analyzed accordingly.Results LSAS subscale scores were significantly correlated with metabolic activity in specific brain regions.In the Safren model,the score for the observation by others subscale was positively correlated with the left fusiform gyrus(P<0.001,false discovery rate[FDR]-corrected)and the left caudate tail(P<0.001,FDR-corrected),suggesting a close association between mood states related to observation by others and the metabolic activity in these regions.In the Baker model,the score for the eating and drinking subscale was negatively correlated with the right precuneus(P<0.001,FDR-corrected),while the score for the assertiveness subscale was positively correlated with the left caudate nucleus(P<0.001,FDR-corrected).These findings revealed the complex associative patterns between various mood and behavioral dimensions and metabolic activities in specific brain regions.Conclusion Social anxiety symptoms are closely associated with metabolic changes in specific brain regions,including the left insula,left caudate tail,and right precuneus.Moreover,different social situations activate distinct brain regions.Compared with individuals with social anxiety disorder,normal individuals exhibit involvement of fewer brain regions when experiencing social anxiety.These findings provide new experimental evidence for understanding the neural mechanisms underlying social anxiety.

Objective: To investigate the molecular regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) in mechanical stress-induced inflammatory cytokine expression in human periodontal ligament cells (hPDLCs), providing a theoretical basis and potential therapeutic target for inflammatory control during orthodontic treatment. Methods: This study was approved by the Institutional Ethics Committee. Primary human periodontal ligament cells (hPDLCs) were isolated and cultured in vitro. Self-renewal capacity was confirmed via colony-forming assays, while osteogenic and adipogenic differentiation potential was evaluated via Alizarin Red S staining, alkaline phosphatase (ALP) activity assays, and Oil Red O staining. An in vitro compressive force stimulation model (1.5 g/cm2, 12 h) was established to compare inflammatory cytokine expression of hPDLCs—interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and HIF-1α—between the Control group (no mechanical stimulation) and the Force group (1.5 g/cm2, 12 h) using quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence (IF) staining. Mechanically induced HIF-1α-regulated gene expression changes were analyzed through transcriptomic sequencing. To explore pharmacological inhibition, the small-molecule HIF-1α inhibitor LW-6 was applied at varying concentrations (10 μmol/L, 30 μmol/L, 50 μmol/L) to optimize the treatment dose. Subsequently, qRT-PCR, Western blot, and IF staining were conducted to evaluate inflammatory cytokine of hPDLCs and HIF-1α expression in three groups: Control (no force), Force (1.5 g/cm2, 12 h), and Force+LW6 (1.5 g/cm2, 12 h + 30 μmol/L LW-6). Results: Primary hPDLCs demonstrated self-renewal capacity along with osteogenic and adipogenic differentiation potential. Compared to the Control group, the Force group exhibited significantly increased mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6, and TNF-α, along with enhanced fluorescence intensity of IL-1β and TNF-α. Transcriptomic analysis revealed that mechanical compressive force activated the HIF-1 signaling pathway, which subsequently mediated inflammatory responses and bone remodeling processes in hPDLCs. Furthermore, the mRNA and protein levels of HIF-1α were considerably elevated in the Force group compared to the Control group. Treatment with LW-6 (10, 30, or 50 μmol/L) effectively suppressed HIF-1α expression, with 30 μmol/L LW-6 identified as the optimal concentration for intervention. In subsequent experiments, the Force group showed significant upregulation in mRNA/protein expression of IL-1β, IL-6, and TNF-α compared to the Control group, as well as intensified HIF-1α, IL-1β, and TNF-α fluorescence signals. Conversely, the Force+LW6 group (mechanical force + 30 μmol/L LW-6) exhibited a notable reduction in inflammatory cytokine expression levels and a weakening of HIF-1α, IL-1β, and TNF-α fluorescence signals compared to the Force group. Conclusion HIF-1α potentiates mechanical stress-induced inflammatory responses in hPDLCs and may serve as a promising therapeutic target for mitigating orthodontic-associated periodontal inflammation.

Abstract To explore the influence of the occurrence and development of bystander behavior in cyberbullying among adolescents, the paper reviews the factors influencing bystander behavior from the perspective of social ecosystem theory at the individual level, microsystem (family and school factors), peripheral system (contextual factors), macrosystem (cultural factors) and digital environment (media factors). It is pointed out that the future research needs to further explore the internal interaction of micro system, the influence of time system and technological development on bystanders, and the complex interaction between social ecosystems, and design feasible intervention strategies to transform passive bystanders into active interveners.

AIM:To investigate alterations in the expression levels of inflammatory cytokines and subsets of CD8+ T cells in the peripheral blood of patients with diabetic retinopathy(DR).METHODS:Retrospective study. A total of 40 patients with type 2 diabetes admitted to Xi'an People's Hospital(Xi'an Fourth Hospital)from April to July 2022 were recruited for this study and categorized into two groups: 20 cases in the simple type 2 diabetes mellitus(DM)group, and 20 cases in the DR group. Additionally, 20 healthy individuals undergoing routine physical examinations served as the control group. The expression levels of cytokines, including interleukin(IL)-6, IL-8, and IL-10 in peripheral blood were quantified using ELISA. Flow cytometry was employed to analyze the expression of programmed cell death-1(PD-1), T cell immunoglobulin domain and mucin domain protein-3(TIM-3), CD28, and CD57 on CD8+ T cells.RESULTS:The peripheral blood expression of IL-6, IL-8, and IL-10 inflammatory cytokines were significantly elevated in DR patients as detected by ELISA(all P<0.001); flow cytometry analysis showed that the expression of PD-1, TIM-3, and CD57 were elevated in peripheral blood CD8+ T cells of DR patients(all P<0.001), and the expression of CD28 was decreased(all P<0.001).CONCLUSION:In DR patients, CD8+ T cells may undergo depletion and senescence as a result of elevated pro-inflammatory cytokines, including IL-6, IL-8, and IL-10.