Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

This study aims to establish BHK-21 stable cell lines expressing APN from four species(human,pig,dog,and cat),the APN fragments were amplified from pEGFP-C1-APN plasmids of the four species stored in the laboratory to generate the recombinant plasmids pcDNA4.0-APN.Af-ter the recombinant plasmids were transfected into BHK-21 cells,the stable BHK-21 cell lines ex-pressing the APNs were selected by two rounds of limited dilution.The constructed BHK-21 cell lines were identified by indirect immunofluorescence assay(IFA),and their susceptibility to PD-CoV and TGEV was tested for these four cell lines.Virus infection experiments revealed that PD-CoV infected cells expressing human,pig,and dog APNs,while it did not infect cells expressing cat APN.Simultaneously,TGEV infected cells expressing pig,dog,and cat APNs,but did not infect cells expressing human APN.The results suggest that the risk of cross-species infection for different coronaviruses and the established cell line can be used effectively to evaluate the virus in-fection.The findings also revealed that PDCoV has the potential risk of cross-species infection of human and dog,and TGEV has the potential risk of cross-species infection of dog and cat.These results provide a basis for the prevention and control strategy of coronaviruses.

Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,and China is facing a severe challenge of rapidly increasing MASLD burden.Beverages,as an important modifiable factor,have become a research focus for primary prevention and lifestyle management of MASLD.This article reviews beverage consumption trends,provides an in-depth analysis of the mechanisms and health effects of sugar-sweetened beverages,alcoholic drinks,coffee,and tea on MASLD,summarizes their potential pathogenic and protective pathways,and explores comprehensive strategies including beverage intervention,lifestyle coordination,functional beverage development,psychological and behavioral mechanism regulation,and targeted population prevention.The aim is to provide theoretical basis and practical guidance for the localized and precise prevention and control of MASLD.

Objective:To explore the molecular mechanism of miR-4508 regulating the inflammatory response of human bronchial epithelial cells induced by representative chrysotile asbestos.Methods:The chrysotile asbestos was ground into ultrafine dust using a horizontal planetary instrument, and human bronchial epithelium (16HBE) cells were taken as the object of infection. Cell survival rate was detected by cell counting kit-8 method, cytotoxicity was detected by lactate dehydrogenase (LDH) kit. The released of inflammatory factor IL-6 was detected by electrochemical luminescence. The released inflammatory factor IL-8 was detected by enzyme-linked immunosorbent assay. The expression level of miR-4508 was screened and verified by reverse transcription-quantitative real-time polymerase chain reaction. After 16HBE cells were treated with AKT inhibitor MK2206, the phosphorylation levels of AKT and PTEN were detected by western blot. The expression levels of AKT and PTEN and the contents of IL-6 and IL-8 were detected in miR-4508 overexpression and interference experiments.Results:With the increase of chrysotile asbestos exposure concentration, the cell survival rate decreased in a concentration-dependent manner, and the LDH content gradually increased. The secretion of IL-6 and IL-8 in chrysotile 25, 50 and 75 μg/ml groups were (325.92±8.61) pg/ml, (331.51±4.96) pg/ml, (378.74±13.77) pg/ml, and (94.95±3.11) pg/ml, (357.60±1.80) pg/ml, (537.19±3.11) pg/ml, respectively, while the group with 0 μg/ml chrysotile was (95.85±1.20) pg/ml and (7.81±0.00) pg/ml ( P＜0.05). In addition, chrysotile asbestos exposure to 16HBE could induce the high expression of miR-4508 . After pretreatment with MK2206, the phosphorylation levels of AKT and PTEN were decreased, the contents of IL-6 and IL-8 were significantly decreased, and the expression level of miR-4508 was significantly reduced. Overexpression of miR-4508 significantly increased the expressions of AKT and PTEN, and the contents of IL-6 and IL-8 ( P＜0.01). After interfering with miR-4508, the expressions of AKT and PTEN were significantly decreased, and the contents of IL-6 and IL-8 were significantly decreased ( P＜0.01). Conclusions:Chrysotile asbestos can induce the inflammatory response of 16HBE cells and up-regulate the expression level of miR-4508. The up-regulation of miR-4508 promotes the 16HBE inflammatory response induced by chrysotile asbestos through the PI3K/AKT pathway.