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.

A Salmonella bacteriophage,PJN025,was isolated from wastewater and characterized for its biological properties,including whole-genome sequencing and assessment of therapeutic poten-tial in animal infection models.Transmission electron microscopy classified it within the Caudovi-ricetes family.PJN025 selectively lysed S.typhimurium and S.enteritidis with an incubation period of approximately 10 min,a burst time of 80 min,and an average burst size of approximately 132 PFU/cell,demonstrating effective bactericidal activity.The phage showed robust stability at temperatures ranging from 30 to 70 ℃ and pH levels from 3 to 12.Whole-genome sequencing re-vealed a complete genome length of 46 478 bp with a G+C content of 45.9％,consisting of 82 open reading frames and one tRNA.No known virulence or resistance genes were found.In Galleria mellonella infection model,a survival rate of 70％was achieved with a preventative dose of 1 × 108 PFU/mL PJN025,compared to a 5％survival rate in the positive control group after 48 h of bacterial challenge.In SPF mice infected with S.typhimurium via intraperitoneal injection,all mices in the positive control group died within five days.However,in the co-infection group treated with 1×108 PFU/mL PJN025,a promising survival rate of 60％was observed.This study showed that the bacteriophage PJN025 had strong specificity,high lytic efficiency,good acid and alkali tol-erance,strong heat resistance,and good safety and prevention effects,providing materials and ex-perimental basis for the development of subsequent phage products.

Objective To explore the impact of ondansetron's use within 24 h before delirium assess-ment in ICU patients on the risk of delirium occurrence.Methods All data were derived from the Critical Care Medical Information Database(MIMIC)-Ⅲ,MIMIC-Ⅳ and the eICU Collaborative Research Database.The research subjects were the patients who were admitted to ICU for treatment for the first time and had re-cords of delirium assessment.The research variable was whether ondansetron was used within 24 h before de-lirium assessment.The main observation indicator was whether delirium occurred after the patient entering to ICU,and whether the patient died during hospitalization or was discharged and returned home was taken as the secondary observation indicator.The propensity score matching eliminated confounding factors,and the stepwise logistic regression and nearest neighbor matching were used to analyze the influencing factors.Results A total of 78 364 patients had the delirium assessment records,among them 22 158 patients had the positive assessment results.A total of 294 patients who used ondansetron within 24 h before delirium assess-ment were taken as the ondansetron group,and 78 070 patients who did not use ondansetron were taken as the control group.Propensity score matching corrected most of the covariates between the two groups.The results of multivariate logistic regression analysis showed that the use of ondansetron was a protective factor for the delirium occurrence(OR=0.72,95％CI:0.53-0.96),and the results of nearest neighbor matching analysis also supported this association(OR=0.48,95％CI:0.31-0.76).However,the use of ondansetron had no effect on the outcome of in-hospital death or discharge home for critically ill patients(P＞0.05).Conclusion Ondansetron may be an effective drug for the prevention or treatment of delirium in critically ill patients.

[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.

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.

This study was aimed at investigating the effectiveness of various host nucleic acid removal and non-specific amplifica-tion techniques in animal tissue samples,to increase the accuracy of pathogen identification in tissue samples.Simulated samples were prepared with a mixture of mouse lung tissue homogenates and Klebsiella pneumoniae fluids,and processed with six host nucleic acid removal kits and three non-specific amplification techniques.The effectiveness of each method in removing host DNA and enriching nucleic acids of pathogenic microorganisms was evaluated through real-time fluorescence quantitative PCR and high-throughput se-quencing.For host nucleic acid removal techniques,the method of selective cleavage and quantitative degradation of host DNA(Com-plete5 kit)effectively decreased the host nucleic acid content in tissue samples and increased the relative abundance of pathogen nucleic acids.In contrast,the magnetic bead method for host DNA removal(Next microbiome DNA enrichment Kit kit)was less effec-tive.At lower pathogen concentrations(77 CFU/mL),the Vazyme kit was more effective than the other kits in removing host nucleic acids.Non-specific amplification techniques(MALBAC whole genome amplification,MDA isothermal amplification,and random primer amplification)were not applicable to tissue samples and were not effective in increasing the relative abundance of pathogen nucleic acids.Selective lysis and quantitative degradation of host DNA were suitable for processing tissue samples with high host back-ground and low pathogenic microorganism levels,whereas non-specific amplification methods were not applicable to tissue samples for pre-processing of macro-genome high-throughput sequencing.

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 diagnostic value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)combined with Doppler ultrasound and elastography in breast lesions.Methods A total of 91 patients with breast lesions confirmed by pathology were retrospectively selected and underwent DCE-MRI,Doppler ultrasound and elastography examinations.The imaging features of benign and malignant breast lesions were analyzed.The diagnostic value of DCE-MRI,Doppler ultrasound,and elastogra-phy in benign and malignant breast lesions were analyzed.Results Among the 91 cases,there were 62 cases with benign lesions(benign group)and 29 cases with malignant lesions(malignant group).There were statistically significant differences in DCE-MRI parameters,Doppler ultrasound parameters and elastography parameters between the two groups(P<0.05).Binary logistic regres-sion analysis found that enhancement characteristics,morphology,time-signal intensity curve(TIC),blood flow signals on Doppler ultrasound,elastography score,and strain rate(SR)were the influencing factors of benign and malignant breast lesions(P<0.05).The differential diagnostic efficacy of combination of the three examinations was highest.The sensitivity,specificity and accuracy were 88.71%,82.76%and 86.81%,respectively.Conclusion DCE-MRI,Doppler ultrasound,and elastography are effective for differentiating benign and malignant breast lesions.Combination of them can improve the diagnostic performance.