Ferroptosis, an iron-dependent form of programmed cell death characterized by lipid peroxidation, oxidative stress, and dysregulated iron metabolism, plays a significant role in the pathogenesis of glaucoma. This review systematically summarizes the fundamental mechanisms of ferroptosis, the involvement of oxidative stress and ferroptosis in glaucoma, the relationship between ferroptosis and glaucomatous neurodegeneration, and the potential therapeutic strategies targeting ferroptosis in glaucoma. Studies have shown that ferroptosis-regulating factors play a crucial role in mitigating oxidative damage and preserving cellular function. However, the complexity of their regulatory mechanisms not only hinders a comprehensive understanding of their roles but also impedes clinical translation. Although ferroptosis inhibitors have demonstrated promising neuroprotective effects in animal models, their clinical application remains challenged by issues such as drug safety and target specificity. Therefore, the development of more targeted and low-toxicity therapeutic strategies is essential to advance personalized and precise treatment for glaucoma.

Objective To analyze the clinical characteristics of recipients with interstitial lung disease (ILD) who underwent second lung transplantation and summarize the diagnostic and therapeutic experience. Methods A retrospective analysis was conducted on the clinical data of 14 patients who underwent first and second lung transplants for ILD at the First Affiliated Hospital of Guangzhou Medical University from January 2015 to December 2024. The preoperative conditions, intraoperative events, postoperative treatments and prognoses of the first and second lung transplantation were compared, and the postoperative survival of ILD patients after the second lung transplantation was analyzed. Results Among the 14 recipients of the second lung transplant, 13 underwent the procedure due to chronic lung allograft dysfunction, and 1 due to airway complications. The median interval time from the first to the second lung transplant was 32 (2, 80) months. Before the second transplantation, 2 recipients required endotracheal intubation and mechanical ventilation, and 2 required endotracheal intubation, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO) support. The surgical time for the second lung transplantation was longer than that for the first, with increased intraoperative red blood cell and plasma transfusion volumes, the proportion of ECMO support during the second lung transplantation was higher than that during the first (all P<0.05). However, the cold ischemia time for one-sided lung transplant completion in the first lung transplant was similar to that in the second lung transplantation (P>0.05). The median follow-up time after the second lung transplantation was 32 (1, 63) months. The 1-month, 6-month and 1-year survival rates after the second lung transplantation were 79%, 57% and 50%, respectively, with causes of death being infection, multiple organ failure and gastrointestinal bleeding. Conclusions For ILD patients undergoing second lung transplantation after the first lung transplantation, the second lung transplantation is more challenging, with longer surgical time and higher intraoperative blood loss. It requires higher surgical skills and perioperative management. Non-emergency second transplantation may still achieve good results.

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans ; Uterine Cervical Neoplasms/pathology* ; Oncolytic Viruses/genetics* ; Female ; HEK293 Cells ; Oncolytic Virotherapy/methods* ; Adenoviridae/genetics* ; Gene Editing/methods* ; Telomerase/genetics* ; Adenovirus E1A Proteins/genetics* ; Genetic Vectors/genetics* ; HeLa Cells

Objective: To explore the causal relationship between adolescent school connectedness and the co-occurrence with health risk behaviors among junior high school students, so as to provide the reference for reducing the occurrence of adolescents health risk behaviors among junior high school students. Methods: A total of 924 students from two junior high schools in Jishou City were selected by the convenience sampling and cluster sampling methods, and two follow up surveys were conducted at 6 month intervals in April (T1) and October (T2) of 2023 using the Adolescent Health Risk Behavior Questionnaire and the School Connection Scale. The scores of the co-occurrence of school connectedness and health risk behaviors among junior high school students were compared by different survey periods and genders using the t-test, and cross lagged analyses were performed using Mplus 8.3 software. Results: School connectedness scores among junior high school students in T1 and T2 surveys were (38.86±7.46) (37.87± 7.71 ) and co-occurrence of health risk behaviors scores were (1.64±0.68) (1.83±0.53), respectively, and the differences between the scores of the 2 surveys were statistically significant ( t=4.24, -4.14, P <0.05). The correlation between school connectedness and co-occurrence of health risk behaviors were statistically significant in both surveys ( r =-0.46 to -0.33, P <0.05). Cross lagged analyses showed that school connectedness in T1 negatively predicted the co-occurrence of health risk behaviors in T2 ( β =-0.08), and the co-occurrence of health risk behaviors in T1 negatively predicted the school connectedness in T2 ( β =-0.15) ( P <0.05). Conclusions There is a longitudinal causal relationship between school connectedness and co-occurrence of health risk behaviors among junior high school students. School connectedness should be improved through various ways to reduce the co-occurrence of health risk behaviors.

OBJECTIVE To establish the quality standard of Triadica cochinchinensis and to perform the acute toxicity study. METHODS Appearance properties, powder microscopic identification, and thin-layer chromatography(TLC) identification were researched. The specific chromatogram was established by HPLC. The content of cadmium(Cd), lead(Pb), arsenic(As), copper(Cu), and mercury(Hg) was determined by inductively coupled plasma-mass spectrometry(ICP-MS). Acute toxicity was studied by maximum dose. RESULTS The outer skin of herbs was dark brown, and the inner surface was light yellow brown and fibrous. Besides, crystal sheath fiber was common, and calcium oxalate clusters arranges in rows. In the TLC diagram of the test product, the fluorescent spots of the same color were displayed at the corresponding position of the control product(scopoletin, isofraxidin). Five common peaks were calibrated in the characteristic map and the three characteristic peaks(scopoletin, isofraxidin, dimethylfraxetin) were recognized. The content of the measured heavy metal elements was lower than the national limit standard. The linear correlation coefficient was R2 > 0.999. The precision, stability, repetitive RSD were < 10%. The average recovery rate of the added sample was 80%−120%, and the RSD was < 10%. The maximum dose of the acute toxicity test was 184.09 g·kg−1. The 14 d internal body mass, food intake, organ-body ratios, the serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, blood urea nitrogen, and creatinine were not significantly different by comparing with the normal controls. Therefore, no significant toxicity was observed. CONCLUSION The established standard can provide a reference for evaluating the quality of Triadica cochinchinensis. The heavy metal content of ten batches of medicinal materials is within the safe range. Acute toxicity test show that there is no obvious significant adverse teactions after oral administration, and the safe dose range is large, which can provide a reference for the subsequent development and utilization.

OBJECTIVE In the process of drug dispensing, using computer vision technology to identify drugs is vulnerable to the influence of lighting, angle, packaging and other factors, which will produce large identification errors. Therefore, this paper proposes an object detection algorithm for drug appearance recognition(YOLOv4-GhostNet-CMB). METHODS Firstly, the algorithm redesigned the backbone feature extraction network in YOLOv4 by using GhostNet. Secondly, the CA attention model was brought into the Ghost module, aggregate features along horizontal and vertical directions to enhance the precise positioning of drugs. Finally, Bi-FPN feature pyramid structure was introduced to connect with the new backbone, and added a feature graph output which could enhance feature extraction and improved the detection accuracy of drugs. RESULTS The experimental results show that the average detection accuracy of YOLOv4-GhostNet-CMB algorithm reached 92.24%, which was a significant improvement of 4.49% compared with YOLOv4 algorithm in term of detection accuracy. CONCLUSION The model size is only 150 MB, nd this algorithm can effectively identify drugs.

Objective To understand the research status of osteoimmunology by a bibliometric study and provide reference for potential research hotspots in the future. Methods The articles and reviews related to osteoimmunology were retrieved from the Web of Science Core Collection with the time interval from 2002 to 2022.VOSviewer,CiteSpace,and the Bibliometrix package in R were used to analyze the contributions and co-citation relationships of countries/regions,institutions,journals,authors,references,and keywords,and identify research hotspots. Results A total of 812 English-language articles published between 2002 and 2022 were collected,and the annual number of articles was increasing year by year.China had the most articles (n=233,28.69%),followed by the United States and Japan.Sichuan University had the highest number of articles (n=35,4.27%).Takayanagi H ranked first among both publishing authors and co-cited authors.Froniters in Immunology was the journal publishing the highest number of articles (n=45,impact factor of 7.3 in 2023) in this field.The clustering of key nodes and identification of keywords in co-cited references indicated that the research of osteoimmunology mainly focused on signal transduction mechanisms of bone immunity,bone immunity-mediated diseases,and drug treatment.In recent years,the research hotspots of osteoimmunology included macrophage polarization,bone biomaterials,bone regeneration,and therapy. Conclusion This study employed bibliometric methods to comprehensively analyze the countries,institutions,authors,keywords,and references of articles in osteoimmunology,providing guidance and reference for researchers engaged in this field.
Humans ; Bibliometrics ; China ; Allergy and Immunology ; Osteology

OBJECTIVE To explore the mechanism of action of active components of Nostoc commune in anti-triple-negative breast cancer(TNBC) by the network pharmacology method and molecular biology experiment. METHODS The active components of Nostoc commune were collected by consulting the literature and combined with the preliminary research in the laboratory, the Swiss Target Prediction database was used for target prediction, and the disease targets were obtained in the TTD, Genecards and OMIM databases. The STRING online platform was used for protein-protein interaction, and the KEGG signaling pathway and GO gene function enrichment analysis were performed using the Metascape database. Molecular docking of N-acetyltryptamine, a component of Nostoc commune, and target AKT1 by AutoDock software. Annexin V-FITC/PI double staining method was performed to analyze the apoptotic rate of cells. RT-qPCR and Western blotting were used to detect the mechanism of action of the active components of Nostoc commune on anti-TNBC. RESULTS The results of network pharmacology showed that there were 8 effective components, such as N-acetyltryptamine, Scytonemin and Nostocionone, involved 75 key targets such as signal transduction and AKT1, STAT3 and CCND1. The KEGG signaling pathway and GO gene function enrichment analysis results involved cancer-related signaling pathways, PI3K-Akt signaling pathways and MAPK signaling pathways. Molecular docking showed that N-acetyltryptamine had better affinity with AKT1. N-acetyltryptamine could not significantly promote apoptosis of breast cancer cells. Western blotting showed that N-acetyltryptamine could down-regulate the protein expressions of AKT1. The results of RT-qPCR showed that N-acetyltryptamine could effectively reduce the mRNA expression of AKT1 in cells. CONCLUSION N-acetyltryptamine may inhibit the proliferation of TNBC cells by inhibiting the AKT1 signaling pathway, thereby exerting anti-TNBC effects.

OBJECTIVE To investigate the therapeutic effect of natural phenolic compound p-hydroxybenzoic acid(HA) on adjuvant arthritis(AA) induced by the complete Freund's adjuvant(CFA), and to clarify the mechanism of HA preliminary. METHODS Apart from the normal group, all rats received 0.1 mL CFA by plantar subcutaneous injection to induce AA rats model. And rats with AA were randomized to the model group, the low-, medium-, and high-dose HA group(2.5, 5, and 10 mg·kg-1, respectively), the positive control group(indomethacine, 5 mg·kg-1). The rats in each group were orally treated with the corresponding drugs for therapeutic intervention. The volume and leg thickness of the rats in each group were recorded and an inflated articular score was obtained. Inflammation cytokine expression(TNF-α, IL-1β and IL-6) was determined by ELISA and qPCR. Radiographs and HE staining were used to observe histopathological and pathological changes in the foot. The expressions of caspase-1 and NF-κB were examined in Western blotting. RESULTS HA could significantly alleviate joint swelling in AA rat(P<0.05), inhibited the production of inflammatory factors(TNF-α, IL-1β and IL-6) from protein and mRNA levels(P<0.05), and decreased the expression levels of caspase-1 and NF-κB at protein level(P<0.05). HA alleviated ankle injury in rats by X-ray examination, and HE staining showed that HA could significantly inhibit the infiltration of inflammatory cells and the destruction of cartilage surface(P<0.05), and these results were dose-dependent. CONCLUSION HA may relieve rheumatoid arthritis by inhibiting the NF-κB/casepase-1 signaling pathway.