AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

Objective: To analyze characteristics of hepatitis B infection in HBsAg-/HBV DNA+ blood donors in Taiyuan, so as to provide evidence for adjusting blood screening strategies. Methods: Blood samples of HBsAg-/HBV DNA+ donors were tested using enzyme-linked immunosorbent assay (ELISA), chemiluminescence assay, nucleic acid qualitative test, and nucleic acid quantitative test. Data on HBsAg-/HBV DNA+ donors in Taiyuan region from January 1, 2016 to December 31, 2024 were statistically analyzed to evaluate the detection rate, demographic characteristics, influencing factors of detection rate, nucleic acid quantitative results, and serological patterns of HBsAg-/HBV DNA+ donors. Results: From January 1, 2016 to December 31, 2024, 991 565 donor samples underwent nucleic acid testing in Taiyuan. A total of 309 HBsAg-/HBV DNA+ samples were detected, resulting in an HBsAg-/HBV DNA+ detection rate of 3.12 per 10 000. The detection rate varied significantly across different years (P<0.05). Males had a significantly higher HBsAg-/HBV DNA+ detection rate than females, first-time donors had a higher rate than repeat donors, and whole blood donors had a higher rate than apheresis donors (P<0.05). The detection rate also differed significantly among age groups (P<0.05). Logistic regression analysis showed that gender, age, donation frequency, and donation type were all influencing factors for HBsAg-/HBV DNA+ detection (all P<0.05). The predominant serological patterns among HBsAg-/HBV DNA+ donors were HBsAb+/HBcAb+ (43.69%, 135/309) or HBcAb+ alone (24.27%, 75/309). Viral load was detectable in 53.40% (165/309) of the HBsAg-/HBV DNA+ donors. Among these, 61.21% (101/165) donors had a viral load<20 IU/mL, and 94.55% (156/165) had a viral load<200 IU/mL. Donors with viral load<200 IU/mL primarily exhibited HBsAb+/HBcAb+ (41.67%, 65/156) or HBcAb+alone (36.54%, 57/156) serological patterns. Conclusion: The prevalence of HBsAg-/HBV DNA+ is low among blood donors in Taiyuan. Higher detection rates were observed in the 46-55 years age group, males, first-time donors, and whole blood donors. HBsAg-/HBV DNA+ donors exhibit specific serological patterns and generally have low viral loads, indicating a potential residual transfusion risk. It is recommended to add HBcAb testing, together with high-sensitivity nucleic acid testing technologies and donor follow-up, to ensure blood safety and guide donor reentry.

Objective: To optimize the technology and process for recovering immune cells from discarded leukocyte filter through reverse flushing, and to investigate the effects of different reverse flushing solutions and physical conditions (temperature, soaking, and ultrasound) on the cell recovery rate. Additionally, to evaluate the feasibility and quality of isolating and culturing NK cells from the recovered cells. Methods: Normal saline, PBS, and PBS-EDTA were used as reverse flushing solutions to backwash the filter, and the white blood cell recovery rates were compared. The reverse flushing efficiency was optimized by adjusting the temperature of the reverse flushing solution, filter soaking treatment and ultrasonic treatment. The Ficoll separation method was employed to isolate peripheral blood mononuclear cells (PBMCs) from the elution solution and conduct in vitro expansion and culture. Lymphocyte subsets were identified and quantified using flow cytometry. Results: The physiological saline served as the backflush fluid was the most stable. The reverse temperature had a significant impact on the recovery rate of white blood cell subgroups. The recovery rates of lymphocytes and monocytes at 37℃ were significantly higher than those at 4℃ [(35.56±5.55)% vs (22.88±0.31)%, (32.42±4.82)% vs (8.00±1.6)%, t=5.581 and 5.758, respectively, both P<0.001)], and at 25℃ [(35.56±5.55)% vs (22.42±6.13)%, t=5.904, P<0.001; (32.4±4.82)% vs (21.11±1.23)%, t=2.629, P=0.030)]. The recovery rates of white blood cell subgroups after 37℃ immersion were higher than those after direct reverse flow at 37℃, but the difference was not statistically significant (P>0.05). The recovery rate of cells after ultrasonic immersion at 25℃ was further increased compared to that after immersion at 25℃, but the difference was not statistically significant (P>0.05). The purity of the NK cells obtained through sorting reached (94.2±4.5)%, and the viability was (94.8±0.9)%. After 15 days of culture, the cell count was expanded approximately 450 times, yielding more than 10 /mL highly active NK cells. Conclusion: By optimizing the backflushing process, immune cells can be efficiently recovered from discarded filters. The 37℃ backflow liquid has the best backflow effect; soaking and ultrasonic treatment can be used as auxiliary methods to improve recovery rates. The NK cells from this source have high purity, good activity, and strong expansion ability, and can be used as a reliable cell source for immunotherapy research, and in line with the circular economy concept of resource reuse.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

Mitochondria not only serve as the central hub for cellular energy metabolism,but also participate in crucial physiological processes such as signal transduction and activity regulation.Abnormal mitochondrial quantity,imbalance in mtDNA copy number,accumulation of genetic mutations,and aberrant activation of autophagic pathways can lead to mitochondrial dysfunction or even organelle disorders,while activating mechanisms of cellular damage and death,consequently contributing to the pathogenesis of various diseases.As a highly selective form of autophagy,mitophagy plays a pivotal regulatory role in organelle quality control and homeostasis maintenance.This article focuses on the classic PINK1/Parkin pathway-mediated mitophagy as an entry point,summarizing recent research advances regarding the role of mitophagy in neurodegenerative diseases,aiming to provide novel insights for developing targeted mitophagy regulation strategies to improve prevention and treatment approaches for neurodegenerative disorders.

Objective To analyze and preliminarily verify key genes and pathways in the transcriptome of peripheral blood of lung adenocarcinoma patients with metastasis bone pain(MBP),and to explore its underlying mechanism.Methods Nine lung adenocarcinoma patients with bone metastasis treated in the First Affiliated Hospital of Sun Yat-sen University from May 2020 to May 2021 were selected for retrospective analysis,including 4 patients with typical MBP clinical manifestations and visual analogue scale(VAS)≥4(MBP group)and 5 patients without suffering any pain(control group).Peripheral blood mRNA sequencing was performed to identify differentially expressed genes(DEGs),followed by functional pathways analysis and protein-protein interaction(PPI)network analysis.The most significant modules and hub genes were confirmed and visualized using Cytoscape software.The target miRNAs regulating these hub genes were predicted using Targetscan database,and long non-coding RNA(lncRNA)interacting with these miRNAs were also predicted using lncBase database.The relationships among lncRNA,miRNA and mRNA were visualized to construct a competing endogenous RNA(ceRNA)network through Cytoscape software,and the nodes of this network were verified using quantitative PCR(qPCR).Results A total of 1466 DEGs were identified,including 666 up-regulated genes and 800 down-regulated genes.Chemokine receptor 3(CXCR3),pro-opiomelanocortin(POMC),neuromedin U receptor 1(NMUR1),chemokine ligand 2(CCL2)and endocannabinoid receptor 1(CNR1)were identified as hub genes.The most significant enriched processes and pathways of DEGs included osteoclast differentiation,NOD like receptor signal transduction pathway,type Ⅰinterferon signal pathway,nuclear factor kappa-B(NF-κB)signal pathway,apoptosis/autophagy pathway,chemokine signal pathway,interleukin(IL)-1β pathway.Two ceRNA networks were identified:MALAT1-hsa-miR-124-3p.2-CCL2 and NEAT1-hsa-miR-325-3p-CXCR3.qPCR results showed that the expression levels of CCL2,CXCR3,MALAT1,NEAT1 and hsa-miR-325 were higher in MBP group than these in control group(P<0.05).Conclusions CXCR3,POMC,NMUR1,CCL2 and CNR1 may serve as key genes in the occurrence of MBP and could be important regulatory targets for MBP.The development of MBP in lung adenocarcinoma may be associated with the dysregulation of the networks:MALAT1-hsa-miR-124-3p.2-CCL2 and NEAT1-hsa-miR-325-3p-CXCR3.

To explore the value of the diaphragm thickness fraction (TF) and diaphragm mobility (DM) measured by ultrasound for predicting ventilator withdrawal success in patients with acute respiratory distress syndrome (ARDS) after cardiac surgery. Methods: This study included 246 patients undergoing the spontaneous breathing trial. Diaphragmatic function was evaluated by ultrasound, including the diaphragm thickness at the end of calm breathing (thickness of the diaphragm at functional residual capacity [TdiFRC]) and the maximum diaphragm thickness at the end of inspiration (thickness of the diaphragm at full vital capacity [TdiFVC]); TF=(TdiFVC–TdiFRC)/TdiFRC×100%. DM, the oxygenation index (the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen), and the rapid shallow breathing index (RSBI) were measured. Results: Successful liberation from mechanical ventilation was observed in 209 patients. There were no significant differences in the TdiFRC (0.3±0.1 cm vs. 0.3±0.1 cm) or TdiFVC (0.3±0.1 cm vs. 0.2±0.1 cm) between the ventilator withdrawal success group and the ventilator withdrawal failure group (P>0.05). The TF was greater in the ventilator withdrawal success group than in the ventilator withdrawal failure group (40.8%±15.8% vs. 37.7%±9.2%, P<0.01). DM in the ventilator withdrawal success group was greater than that in the ventilator withdrawal failure group (1.5±0.5 cm vs. 1.2±0.4 cm, P=0.040). The RSBI was lower in the ventilator withdrawal success group than in the ventilator withdrawal failure group (74.3±25.6 breaths·min–1·L –1 vs. 89.9±34.5 breaths·min–1·L –1, P<0.01). Conclusions: Diaphragmatic ultrasound can be used to predict the success of ventilator withdrawal in patients with ARDS.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Understory planting of medicinal plants is a new planting mode that connects Chinese herbal medicine(CHM) with forest resources.The complex and variable understory environmental factors will inevitably affect the yield and quality of understory CHM.This research summarized the research progress on understory planting of medicinal plants based on forest types and environmental factors within the forest from the perspectives of understory light, air temperature and humidity, soil characteristics, and the interaction between crops within the forest.The results showed that the complex and variable light, temperature and humidity, and soil factors(such as fertility, acidity and alkalinity, and microorganisms) under the forest could affect the yield and quality of medicinal plants to varying degrees through physiological activities such as photosynthesis and respiration, resulting in a significant increase or decrease in yield and quality compared to open field cultivation.In addition, the competition or mutual benefit between different crops within the forest could lead to differences in the yield and quality of understory medicinal plants compared to open field cultivation.A reasonable combination of planting could achieve resource sharing and complementary advantages.Therefore, conducting systematic research on the effects of understory environmental factors on the yield and content of medicinal plants with different growth and development characteristics can provide theoretical guidance and technical references for formulating comprehensive strategies for understory planting of medicinal plants, such as selecting suitable medicinal plant varieties, optimizing planting density, and conducting reasonable forest management, thus contributing to the sustainable development and ecological protection of CHM.
Plants, Medicinal/growth & development* ; Forests ; Soil/chemistry* ; Environment ; Ecosystem ; Temperature