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.

ObjectiveBased on literature data mining， this study explores the modeling elements of diarrhea-predominant irritable bowel syndrome （IBS-D） animal models in China and abroad， providing references and suggestions for improving modeling methods and evaluation indicators. MethodsRelevant literature on IBS-D animal experiments from 2014 to 2024 was retrieved through computer searches in databases such as China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， Chinese Medical Journals Full-text Database， and PubMed. Information on experimental animal species， gender， body weight， modeling methods， modeling periods， intervention controls， modeling standards， and detection indicators was organized. Microsoft Excel 2021 software was used to establish a database and perform statistical analysis to examine the characteristics of IBS-D animal models. ResultsA total of 398 articles that met the inclusion criteria were reviewed. The IBS-D animal models were predominantly established using SD rats， Wistar rats， and C57BL/6 mice. Male animals were more commonly used， with rats typically aged 6-8 weeks and mice aged 4-6 weeks. In terms of interventions， piverium bromide was the main Western medicine， Tongxieyaofang was the primary Chinese medicine， and electroacupuncture was the primary acupuncture method. Among the modeling methods， the multi-factor combined composite modeling approach was the most common. Modeling periods were mainly concentrated between 1-14 days and 15-30 days. The success criteria for modeling were mainly evaluated based on the animal's general condition， fecal appearance， visceral sensitivity， gastrointestinal motility， behavior， and pathology. Detection indicators included apparent indexes， pathological markers， biochemical indicators， oxidative stress， brain-gut peptides， neurotransmitters， inflammatory factors， immune function， intestinal permeability， autophagy， apoptosis， proteins related to relevant signaling pathways， intestinal microbiota and its metabolites， etc. ConclusionThere are various methods for establishing IBS-D animal models， but no unified and universally accepted method has been established. The operation of the same modeling methods and the evaluation standards of the models vary across studies. Based on the results of data mining， the authors suggest that the multi-factor combined composite modeling approach most closely reflects the pathophysiological processes of IBS-D， better simulating the complex clinical symptoms of IBS-D patients， such as abdominal pain and diarrhea， and has a high degree of clinical relevance. This method is relatively recommended. While animal models in general align with Western medicine standards， models incorporating traditional Chinese medicine （TCM） syndromes are relatively few. Therefore， one of the future directions for research is to establish IBS-D animal models that meet the combined clinical disease and syndrome requirements of both Western and Chinese medicine.

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*

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of renal solitary fibrous tumor (SFT).Methods:Five cases of renal SFT with unequivocal diagnoses at the Affiliated Hospital of Qingdao University between January 2011 and July 2025 were subject to analyses of their clinical, morphological, immunophenotypic, and molecular characteristics, accompanied by a literature review.Results:Two males and three females aged between 45 and 62 years were included, all of whom presented with the discovery of a renal mass during routine physical examinations. Gross examination showed that the five tumors were all confined in the kidney. The tumors were nodular with maximum diameters ranging from 2.5 cm to 11.0 cm (mean, 5.8 cm). Upon cross-sectioning, they exhibited gray-white or gray-yellow cut surface. Histologically, the tumor cells exhibited oval or short spindle shapes in four cases, presenting with varying densities and arranged in short bundles, woven patterns, and irregular formation. Various amounts of coarse collagen and scattered staghorn blood-vessels were found in the stroma. In one case (case 5), the tumor cells were long spindle-shaped, densely organized in bundles, and interwoven, exhibiting inconspicuous boundaries, moderate nuclear atypia, and at least 4 mitotic figures per 10 high-power fields. Irregular patchy collagen deposition was particularly prominent at the edges of the tumor tissue. In two cases (cases 3 and 5), scattered and various amounts of renal tubules were observed in the tumor. Two cases (cases 4 and 5) demonstrated focal invasion of the renal parenchyma, although no necrosis was noted. Immunohistochemical staining showed that the tumor cells were diffusely and strongly positive for vimentin and STAT6 in all 5 cases, and positive for CD34. Bcl-2 positivity was present in 4 of the 5 cases. All cases were negative for CKpan, EMA, PAX8, HMB45, Melan A, SMA, and S-100 protein. The p53 status was wild type, and the Ki-67 index ranged from 1% to 8%. Next-generation sequencing was conducted on one case (case 4), revealing the NAB2 (exon 3)::STAT6 (exon 18) gene fusion. The 5 patients were followed up for 1 to 158 months (mean, 56 months), and all were alive with no recurrence or metastasis.Conclusions:SFT of the kidney are rare and morphologically similar to extrarenal SFT. Key morphological features include short spindle-shaped tumor cells arranged in bundles, interwoven patterns or irregularly, accompanied by staghorn blood-vessels and scattered coarse hyaline collagen fibers. SFT with epithelial inclusions may represent a relatively common histological subtype in the kidney. Immunohistochemical staining that demonstrates diffuse and strong positivity for STAT6 and CD34 is instrumental in diagnosing this tumor. The pathogenesis is linked to the centromeric inversion of chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes. Most of these tumors exhibit favorable prognosis.

Objective:To identify the change trajectory of intrinsic capacity in people aged ≥50 years in Shanghai and explore the impact of intrinsic capacity trajectory change on overall function and dalily life activities in this population.Methods:The longitudinal data from round 1 to 3 Study of Global Ageing and Adult Health in Shanghai were used. The total intrinsic ability scores from five dimensions of cognition, psychology, sensory, vitality and locomotion were calculated. The censored normal model of group-based trajectory was used to identify the trajectory of intrinsic capacity change over time. Linear regression model and multivariate logistic regression model were used to analyse the effects of different levels intrinsic capacity trajectory on the scores of the WHO Disability Assessment Schedule (WHODAS), the activity of daily living (ADL) and the instrumental activities of daily living (IADL).Results:A total of 2 302 study participants aged ≥50 years with 3 round complete data were included in this study, and 3 levels of intrinsic capacity trajectory were identified, low-level trajectory (9.3%), medium-level trajectory (41.7%), and high-level trajectory (49.0%). Compared with the high-level group, the medium-level and low-level groups had higher WHODAS scores, which increased by 3.578 (95% CI: 2.028-5.129) and 12.620 (95% CI: 9.951-15.289), respectively, and those with more severe disability and those in the low-level group were at higher risk for severe difficulty in ADLs ( OR=12.450, 95% CI: 4.310-35.966) and IADLs ( OR=5.479, 95% CI: 1.311-22.904). Conclusions:Heterogeneity in trajectory of intrinsic capacity exists in people aged ≥50 years in Shanghai. Middle-aged and elderly people with low initial level and rapid decline trajectory of intrinsic capacity are at greater risk for the decline of daily life ability and the increase of disability. It is necessary to strengthen the long-term dynamic monitoring and evaluation of the change trajectory of intrinsic capacity in this population.

Objective:To investigate the relationship between thoracic aortic calcification (TAC) and autonomic nervous system (ANS) function in patients receiving continuous ambulatory peritoneal dialysis (CAPD).Methods:It was a cross-sectional study. The CAPD patients with dialysis duration >6 months between January and December 2022 were retrospectively enrolled. The baseline clinical data, heart rate variability (HRV) data such as standard deviation of all normal to normal intervals (SDNN), root mean square of successive differences between adjacent normal-to-normal intervals (RMSSD), high frequency (HF), very low frequency (VLF), low frequency (LF), LF/HF, acceleration capacity (AC) and deceleration capacity (DC), and skin sympathetic nerve activity (SKNA) were collected. TAC was defined as TAC score (TACS) >100 AU. The patients were divided into TACS >100 AU group and TACS≤100 AU group based on whether the thoracic aorta was calcified. The differences of those data between the two groups were compared. Logistic regression model was used to analyze the related factors of TAC. Spearman correlation analysis method was used to analyze the correlation between peripheral blood neuropeptide Y, ANS parameters, average amplitude SKNA (aSKNA) and TACS.　Cox regression model was used to analyze the risk factors of all-cause mortality in patients with CAPD.Results:The study included 106 CAPD patients with 50 males (47.2%), age of (46.04±11.10) years and dialysis duration of (41.55±30.52) months. TACS>100 AU group exhibited significantly lower heart rate ( t=2.015, P=0.046), DC ( t=2.131, P=0.035), LF/HF ( Z=3.332, P<0.001) and ln(LF/HF) ( t=3.326, P=0.001), and higher AC ( t=-2.392, P=0.019) than TACS≤100 AU group. Multivariate logistic regression analysis results showed that after adjusting for age and eosinophil count, lnVLF ( OR=0.66, 95% CI 0.45-0.98, P=0.038), lnLF ( OR=0.69, 95% CI 0.49-0.97, P=0.032), DC ( OR=0.79, 95% CI 0.64-0.99, P=0.039) and AC ( OR=1.32, 95% CI 1.04-1.68, P=0.021) were independently correlated with the risk of TAC. Spearman correlation analysis showed that neuropeptide Y level in peripheral blood was correlated with aSKNA ( r=0.23, P=0.017), lnSDNN ( r=-0.20, P=0.036) and TACS ( r=0.19, P=0.048). During the follow-up period of (25.8±4.2) months, 5 patients (4.72%) died, including 1 patient in the TACS≤100 AU group and 4 patients in the TACS>100 AU group. Compared with the survival group, the death group had higher TACS ( Z=-2.262, P=0.024) and lower LF/HF ( Z=-2.750, P=0.006). Cox regression analysis results showed that increased ln(LF/HF) was an independent influencing factor for all-cause mortality in CAPD patients ( HR=0.22, 95% CI 0.05-0.83, P=0.026). Conclusions:HRV parameters (lnVLF, lnLF, AC and DC) of CAPD patients are independently associated with TAC. The dysfunction of ANS in CAPD patients (especially the decreased vagus nerve activity) may promote TAC.

Objective To elucidate the causal relationship between specific immune cells and autoimmune hepatitis(AIH)using a two-sample Mendelian randomization(MR)approach.Methods A bidirectional MR analysis was conducted using data from large publicly accessible Genome-Wide Association Study(GWAS)databases.The inverse variance weighted(IVW)method was employed as the primary method to evaluate the relationship between 731 immune cell traits and AIH.The false discovery rate(FDR)was controlled using the Benjamini-Hochberg correction.Additionally,pleiotropy and heterogeneity tests were performed,and a leave-one-out sensitivity analysis was conducted to further validate the robustness of the results.Results At a significance level of 0.20,it was found that the absolute count of CD28-CD8+regulatory T-cells(IVW:odds ratio[OR]=1.486;95％confidence interval[CI],1.189-1.859;P＜0.001;PFDR=0.185),the level of CD28 on CD39+secreting regulatory T-cells(IVW:OR=1.194;95％CI,1.074-1.328;P=0.001;PFDR=0.185),and the level of CD45 on mononuclear myeloid-derived suppressor cells(IVW:OR=1.243;95％CI,1.108-1.394;P＜0.001;PFDR=0.143)were associated with an increased risk of AIH.The level of programmed death-ligand 1 on CD14+CD16+monocytes(IVW:OR=0.849;95％CI,0.771-0.935;P＜0.001;PFDR=0.185)was associated with a reduced risk of AIH.Conclusion Four immune cell phenotypes associated with AIH risk are identified.Further investigation is needed to validate these findings and explore new therapeutic avenues.

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