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.

Objective:To explore the relationship between 24-hour movement behavior and anxiety in middle school students.Methods:Totally 2 690 students from 8 middle schools in Hubei Province were selected as research subjects.The Health Behavior in School-aged Children,Pittsburgh Sleep Quality Index and Self-Rating Anxiety Scale were used to assess 24-hour movement behavior[i.e.,moderate to vigorous physical activity(MVPA),screen time(ST),and sleep duration(SD)]and anxiety symptoms.The binary logistic regression analysis was per-formed to examine the relationship between 24-hour movement behavior and anxiety for middle school students.Results:In middle school students,the compliance rate of 24-hour movement behavior was 4.2％,that of MVPA being 15.8％,that of ST being 27.1％,that of SD being 64.2％,and the detection rate of anxiety was 21.7％.The binary logistic regression analysis showed that,compared with the situation when three factors met with the 24-hour movement guidelines,the anxiety risk of middle school students increased when single factor(i.e.,MVPA,ST and SD)and some two factors(i.e.,MVPA+ST and MVPA+SD)met 24-hour guidelines,with odds ratios being respectively 2.62,2.22,2.80,2.62,2.52.Conclusion:The detection rate of anxiety in middle school students was probably negatively correlated with the compliance rate of 24-hour movement behavior.

Objective To evaluate the impact of different exercise frequencies on the symptoms,quality of life,and duration of rehabilitative effects in patients with Parkinson's disease(PD).Methods A total of 90 PD patients(Hoehn and Yahr stage ≤3,receiving continuous dopaminer-gic stimulation)admitted in Department of Neurology of Chinese PLA General Hospital were en-rolled and randomly divided into groups G1,G2 and G3,with 30 participants in each group.They received rehabilitation exercises of Parkinson's Wellness Recovery(PWR)1 h per time,at differ-ent frequencies,that is,once(G1),twice(G2)and three times(G3)a week,for totally 6 months.Unified Parkinson's disease rating scale(UPDRS),levodopa equivalent dose,10-meter walk test(10-MWT),Fullerton advanced balance(FAB)Scale,trail making test-A(TMT-A),nine-hole peg test(9-HPT)and Parkinson's disease questionare-39(PDQ-39)were applied to evaluate the efficacy of the rehabilitation.Results The PDQ-39 score was significantly decreased in all the three groups after PWR exercise(P＜0.05,P＜0.01).Compared with the corresponding levels before intervention,the group G2 had obviously lower 10-MWT score and higher FAB score(P＜0.05),and the group G3 obtained notably decreased scores in UPDRS,UPDRS-Ⅲ,10-MWT,TMT-A,9-HPT,and PDQ-39[30.72±11.31 vs 31.41±10.42,P=0.001;19.21±9.72 vs 20.17±8.80,P=0.001;7.38(6.26,8.49)s vs 7.48(6.53,8.56)s,P=0.004;53.97±8.74 s vs 54.07±8.62 s,P=0.026;38.71(33.71,49.71)s vs 38.90(33.78,49.82)s,P=0.001;28.00(14.50,36.00)vs 30.00(15.50,38.50),P=0.001],and increased FAB score[23.00(16.00,33.00)vs 21.00(16.00,32.00),P=0.005].In addition,the patients in the G3 group experienced the most pronounced re-habilitation effect immediately after exercise,but,all aforementioned indicators remained augmen-ted even 4 weeks after exercise.Conclusion Exercise rehabilitation three times weekly can greatly enhance the motor function of PD patients,ameliorate non-motor symptoms,and the overall quali-ty of life,with the beneficial effects persisting for a minimum of 4 weeks.

OBJECTIVE To evaluate the effects of phthalic acid esters(PAEs)on the expression of heme oxygenase-1(HO-1)in HepG2 cells,and to construct an HO-1-based three-dimensional quantita-tive structure-activity relationship(3D-QSAR)model.METHODS ① HepG2 cells were treated with seven types of PAEs:di-(2-ethylhexyl)phthalate(DEHP),di-n-octyl phthalate(DnOP),dimethyl phthalate(DMP),diethyl phthalate(DEP),dihexyl phthalate(DHXP),dimethylglycol phthalate(DMEP),and dibutyl phthalate(DBP),at final concentrations of 0(DMSO,solvent control),0.062 5,0.125,0.25,0.5 and 1 mmol·L-1(n=6)for 48 h at 37℃.The expression level of HO-1 was measured by Western blotting.② A 3D-QSAR model was constructed using comparative molecular similarity indices analysis(CoMSIA)based on the measured HO-1 levels.The applicability domain(AD)of the model was evaluated using the leverage method.Model fitting quality and predictive ability were evaluated via the KNIME Enalos+node to verify model stability.Additionally,molecular docking was performed to validate the binding interactions between PAEs and HO-1.RESULTS ① Compared with the solvent control group,48 h of exposure to 0.062 5 mmol·L-1 PAEs(DMP,DMEP,DEHP,DnOP and DEP)significantly increased HO-1 protein expressions,while 1 mmol·L-1 PAEs(DMP,DBP,DnOP,DEP and DHXP)significantly suppressed HO-1 expressions.② The 3D-QSAR model showed a non-cross-validated coefficient(R2)of 0.996 and a cross-validated coefficient(Q2)of 0.548.All the seven PAEs in the 3D-QSAR model were within the applicability domain(AD)and passed external validation.Molecular docking results indi-cated that DBP,DnOP,DEHP and DHXP exhibited stronger binding affinities to HO-1.CONCLUSION Forty-eight hours of exposure of HepG2 cells to 1 mmol·L-1 PAEs can significantly suppress HO-1 expres-sions.The 3D-QSAR model established in this study provides a potential tool for predicting the HO-1-related toxic effects of novel PAEs.

Drug addiction,also referred to as drug dependence or substance use disorder,is a chronic and recurrent brain disease.Its main characteristics are compulsive drug-seeking behavior,continued use of drugs,and a loss of control over intake.Prolonged use of addictive substances can result in both physiological and psychological dependence.When usage is ceased,individuals may experience intense discomfort,including anxiety,insomnia,nausea,vomiting,and a strong craving for the substances.Drug dependence is classified into two types:physical dependence and psychological dependence.Physical dependence describes a pathological state of adaptation that results from the repeated use of addictive substances,leading to severe withdrawal syndrome upon cessation.Psychological dependence involves a mental craving for addictive substances,which is needed to experience the specific euphoria that follows consumption.Regular or continuous use is required to sustain these euphoric effects.The mechanisms of addiction are complex and influenced by genetic,environmental,and various other factors.They involve higher-level neurological activities,such as memory,reward,and decision-making.Currently,effective treatment methods for drug addiction are insufficient.Due to the complexity of drug addiction,laboratory animal research is essential.Using animal behavioral models to simulate human drug addiction can enhance our understanding of the mechanisms of addiction.This research offers a comprehensive overview of various animal experimental models that explore both physical and psychological dependence.It includes detailed descriptions of the methods and procedures used to assess physical dependence,behavioral sensitization,conditioned place preference,drug discrimination,and self-administration experiments.Additionally,the characteristics of each experimental model are compared,and the relevance of these models is discussed,aiming to provide support for the research on addiction mechanisms and the development of therapeutic methods.

Drug addiction,also referred to as drug dependence or substance use disorder,is a chronic and recurrent brain disease.Its main characteristics are compulsive drug-seeking behavior,continued use of drugs,and a loss of control over intake.Prolonged use of addictive substances can result in both physiological and psychological dependence.When usage is ceased,individuals may experience intense discomfort,including anxiety,insomnia,nausea,vomiting,and a strong craving for the substances.Drug dependence is classified into two types:physical dependence and psychological dependence.Physical dependence describes a pathological state of adaptation that results from the repeated use of addictive substances,leading to severe withdrawal syndrome upon cessation.Psychological dependence involves a mental craving for addictive substances,which is needed to experience the specific euphoria that follows consumption.Regular or continuous use is required to sustain these euphoric effects.The mechanisms of addiction are complex and influenced by genetic,environmental,and various other factors.They involve higher-level neurological activities,such as memory,reward,and decision-making.Currently,effective treatment methods for drug addiction are insufficient.Due to the complexity of drug addiction,laboratory animal research is essential.Using animal behavioral models to simulate human drug addiction can enhance our understanding of the mechanisms of addiction.This research offers a comprehensive overview of various animal experimental models that explore both physical and psychological dependence.It includes detailed descriptions of the methods and procedures used to assess physical dependence,behavioral sensitization,conditioned place preference,drug discrimination,and self-administration experiments.Additionally,the characteristics of each experimental model are compared,and the relevance of these models is discussed,aiming to provide support for the research on addiction mechanisms and the development of therapeutic methods.

OBJECTIVE To evaluate the effects of phthalic acid esters(PAEs)on the expression of heme oxygenase-1(HO-1)in HepG2 cells,and to construct an HO-1-based three-dimensional quantita-tive structure-activity relationship(3D-QSAR)model.METHODS ① HepG2 cells were treated with seven types of PAEs:di-(2-ethylhexyl)phthalate(DEHP),di-n-octyl phthalate(DnOP),dimethyl phthalate(DMP),diethyl phthalate(DEP),dihexyl phthalate(DHXP),dimethylglycol phthalate(DMEP),and dibutyl phthalate(DBP),at final concentrations of 0(DMSO,solvent control),0.062 5,0.125,0.25,0.5 and 1 mmol·L-1(n=6)for 48 h at 37℃.The expression level of HO-1 was measured by Western blotting.② A 3D-QSAR model was constructed using comparative molecular similarity indices analysis(CoMSIA)based on the measured HO-1 levels.The applicability domain(AD)of the model was evaluated using the leverage method.Model fitting quality and predictive ability were evaluated via the KNIME Enalos+node to verify model stability.Additionally,molecular docking was performed to validate the binding interactions between PAEs and HO-1.RESULTS ① Compared with the solvent control group,48 h of exposure to 0.062 5 mmol·L-1 PAEs(DMP,DMEP,DEHP,DnOP and DEP)significantly increased HO-1 protein expressions,while 1 mmol·L-1 PAEs(DMP,DBP,DnOP,DEP and DHXP)significantly suppressed HO-1 expressions.② The 3D-QSAR model showed a non-cross-validated coefficient(R2)of 0.996 and a cross-validated coefficient(Q2)of 0.548.All the seven PAEs in the 3D-QSAR model were within the applicability domain(AD)and passed external validation.Molecular docking results indi-cated that DBP,DnOP,DEHP and DHXP exhibited stronger binding affinities to HO-1.CONCLUSION Forty-eight hours of exposure of HepG2 cells to 1 mmol·L-1 PAEs can significantly suppress HO-1 expres-sions.The 3D-QSAR model established in this study provides a potential tool for predicting the HO-1-related toxic effects of novel PAEs.

Objective To evaluate the impact of different exercise frequencies on the symptoms,quality of life,and duration of rehabilitative effects in patients with Parkinson's disease(PD).Methods A total of 90 PD patients(Hoehn and Yahr stage ≤3,receiving continuous dopaminer-gic stimulation)admitted in Department of Neurology of Chinese PLA General Hospital were en-rolled and randomly divided into groups G1,G2 and G3,with 30 participants in each group.They received rehabilitation exercises of Parkinson's Wellness Recovery(PWR)1 h per time,at differ-ent frequencies,that is,once(G1),twice(G2)and three times(G3)a week,for totally 6 months.Unified Parkinson's disease rating scale(UPDRS),levodopa equivalent dose,10-meter walk test(10-MWT),Fullerton advanced balance(FAB)Scale,trail making test-A(TMT-A),nine-hole peg test(9-HPT)and Parkinson's disease questionare-39(PDQ-39)were applied to evaluate the efficacy of the rehabilitation.Results The PDQ-39 score was significantly decreased in all the three groups after PWR exercise(P＜0.05,P＜0.01).Compared with the corresponding levels before intervention,the group G2 had obviously lower 10-MWT score and higher FAB score(P＜0.05),and the group G3 obtained notably decreased scores in UPDRS,UPDRS-Ⅲ,10-MWT,TMT-A,9-HPT,and PDQ-39[30.72±11.31 vs 31.41±10.42,P=0.001;19.21±9.72 vs 20.17±8.80,P=0.001;7.38(6.26,8.49)s vs 7.48(6.53,8.56)s,P=0.004;53.97±8.74 s vs 54.07±8.62 s,P=0.026;38.71(33.71,49.71)s vs 38.90(33.78,49.82)s,P=0.001;28.00(14.50,36.00)vs 30.00(15.50,38.50),P=0.001],and increased FAB score[23.00(16.00,33.00)vs 21.00(16.00,32.00),P=0.005].In addition,the patients in the G3 group experienced the most pronounced re-habilitation effect immediately after exercise,but,all aforementioned indicators remained augmen-ted even 4 weeks after exercise.Conclusion Exercise rehabilitation three times weekly can greatly enhance the motor function of PD patients,ameliorate non-motor symptoms,and the overall quali-ty of life,with the beneficial effects persisting for a minimum of 4 weeks.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

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*