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.

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

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 dietary patterns of individuals aged ≥50 in Shanghai and analyze their association with frailty.Methods:Using data from the third wave of the Study on Global Ageing and Adult Health in Shanghai conducted between 2018 and 2019. We collected the frequency and average intake of food by the food frequency questionnaire. Factor analysis was used to extract dietary patterns, and a frailty index was constructed using the ratio of the cumulative total score of health deficits to 35 health-related variables considered. We used an ordinal multinomial logistic regression model to analyze the association between dietary patterns and frailty.Results:A total of 3 274 participants aged (67.9±9.2) years were included in the study, including 1 971 (60.2%) men and 1 303 (39.8%) women. We extracted four dietary patterns: high-protein-nuts pattern, potato-bean-vegetable-fruit pattern, poultry-meat pattern, and high-oil-salt pattern. After adjusting for confounding factors, the logistic regression analysis showed that compared with the high-oil-salt pattern, the high-protein-nuts pattern was negatively associated with the risk of higher frailty ( OR=0.743, 95% CI: 0.580-0.951). We did not find an association between dietary patterns and frailty between the different gender groups. In the age group 50-64, the high-protein-nuts and potato-bean-vegetable-fruit patterns were negatively correlated with a higher degree of frailty than the high-oil-salt pattern. In the low-level physical activity group, the high-protein-nuts pattern was negatively correlated with a higher degree of frailty than the high-oil-salt pattern ( OR=0.509, 95% CI: 0.361-0.720). However, we found no significant effect of the high-protein nuts pattern, potato-bean-vegetable-fruit pattern, and poultry-meat pattern on the risk of higher frailty compared to the high-oil-salt pattern in the moderate to high level of physical activity group. Conclusions:Compared to the high-oil-salt pattern, dietary patterns with a higher intake of high-protein nuts, potatoes, legumes, and fruits and vegetables might be associated with a lower risk of higher frailty in residents aged 50-64 years of age than with a high oil and salt pattern. At the same time, it may have a more significant protective effect in people with lower physical activity levels. It is suggested that a diet rich in high-protein foods, nuts, potatoes, beans, vegetables, and fruits may help reduce and delay the risk of frailty.

Objective:To understand the association between vitamin D level and grip strength in people aged ≥50 years in Shanghai.Methods:Data were obtained from the WHO's Study on Global Ageing and Adult Health in Shanghai during 2018-2019. Logistic regression model was used to analyze the association between vitamin D level and grip strength, and a stratified analysis was conducted for different gender, age and dairy product intake groups. Restricted cubic spline was used to evaluate the dose-response association between vitamin D level and low grip strength.Results:A total of 4 391 participants were included in the study, including 2 054 men (46.8%), with an average age of (67.02±8.81) years. And 1 421 individuals (32.4%) had low grip strength; 1 533 individuals (34.9%) had vitamin D deficiency, and 401 individuals (9.1%) had vitamin D deficiency. After adjusted for confounding factors, the logistic regression results analysis showed that individuals with vitamin D deficiency had a higher risk for low grip strength ( OR=1.41, 95% CI: 1.09-1.83). In men, after adjusting for confounding factors, vitamin D deficiency was positively associated with the risk for low grip strength ( OR=1.67, 95% CI: 1.12-2.50), but there was no significant association between vitamin D level and grip strength in women ( OR=1.30, 95% CI: 0.97-1.74). In age group 60-69 years and ≥80 years, there was significant association between vitamin D deficiency and low grip strength after adjusting for confounding factors ( OR=1.57, 95% CI: 1.05-2.35; OR=2.40, 95% CI: 1.08-5.31). In people who had daily intake of dairy product <250 ml, there was positive association between vitamin D deficiency and low grip strength, but there was no significant association in people who had daily dairy product ≥250 ml after adjusting for confounding factors. The restrictive cubic spline demonstrated that risk of low grip strength might decreased with the increase of vitamin D levels, however, the difference was not significant ( P>0.05). Conclusions:This study demonstrated that there is association between vitamin D level and grip strength. People with vitamin D deficiency have higher risk for low grip strength.

Background Chrysotile is widely used in construction and industry. Research has shown that it is associated with lung fibrosis in occupational groups, but the involvement of microRNAs (miRNAs) in chrysotile-induced lung fibrosis has been less well studied, and the specific mechanism is still unclear. Objective Using next-generation sequencing technology to analyze the effects of chrysotile exposure on the miRNAs expression profiles of human lung epithelial cells (BEAS-2B cells), to explore the variations of differentially expressed miRNAs and related signaling pathways, and to identify potential targets and molecular mechanisms of chrysotile-induced lung fibrosis. Methods Chrysotile was analyzed with a laser particle size analyzer and an X-ray diffractometer for particle size and physical phase. BEAS-2B cells were exposed to chrysotile for designed time sessions (12, 24, and 48 h) and doses (0, 50, 100, and 200 μg·mL⁻¹). Cell viability was detected with a cell viability assay kit (CCK8); expression levels of Fibronectin, Collagen-Ⅰ, and α-smooth muscle actin (α-SMA) were detected by Western blot after exposure to 200 μg·mL⁻¹ chrysotile for 24 h. Sample correlation and changes in miRNAs expression profiles between the chrysotile-exposed and the control groups were analyzed by next-generation sequencing technology. The target genes of differentially expressed miRNAs were predicted and subjected to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results The average particle size of the chrysotile dust sample used in this study was 3.58 μm, and the results of X-ray diffraction analysis confirmed the characteristic peaks of chrysotile. Compared with the control group, the chrysotile gradually inhibited the survival rate of BEAS-2B cells with increasing concentration and exposure time (P<0.01). The survival rates of the 50, 100, and 200 μg·mL⁻¹ chrysotile-exposed cells after 12 h exposure were 83.88%±1.86%, 78.07%±3.97%, and 71.95%±2.99%, respectively; the survival rates after 24 h exposure were 77.41%±1.58%, 69.57%±2.23%, and 62.79%±3.65%, respectively; the survival rates after 48 h exposure were 74.31%±4.93%, 65.84%±2.71%, and 52.74%±6.31%, respectively. The Fibronectin, Collagen-Ⅰ, and α-SMA protein expression levels were elevated in the 200 μg·mL⁻¹ chrysotile-exposed BEAS-2B cells (P <0.05). The results of principal component analysis showed that there were differences in the composition of the samples between the chrysotile exposure group and the control group, and a total of 163 differential miRNAs were screened, of which 79 were up-regulated and 84 were down-regulated. The results of GO analysis showed that the differential miRNAs were mainly associated with biological processes such as regulation of transcription by RNA polymerase II, regulation of DNA templated transcription, cellular differentiation, protein phosphorylation, lipid metabolism, and cell cycle, cellular components such as nucleus, cytomembrane, cytoskeleton, mitochondria, and endoplasmic reticulum, as well as molecular functions such as protein binding, metal ion binding, transferase activity, and DNA binding. The results of KEGG analysis revealed that the differential miRNAs were mainly enriched in cancer pathway, phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway, Ras-associated protein 1 (Rap1) pathway, calcium pathway, cyclic guanosine monophosphate/ protein kinase G (cGMP-PKG) pathway, Hippo pathway, cyclic adenosine monophosphate (cAMP) pathway, and Ras pathway. Conclusion Chrysotile exposure could significantly inhibit BEAS-2B cell survival, elevate the expression of lung fibrosis-associated proteins, and induce differential miRNAs expression, affecting biological processes (such as lipid metabolism, protein phosphorylation, and cell cycle) and cell components (such as mitochondria and endoplasmic reticulum), and interfering with PI3K/AKT pathway, Hippo pathway, cAMP pathway, Rap1 pathway, and Ras pathway.

Objective To adopt the systematical evaluation method to compare the efficacies between endoscopic retrograde appendicitis therapy (ERAT) versus laparoscopic appendectomy (LA) for treating feca-lith incarceration appendicitis.Methods The databases of PubMed,WANGFANG,CNKI,Cochrane Library and Embase were retrieved by computer.The retrieval time was 2016-2021.The EART related clinical trials were collected,the literatures conforming to the inclusion standard conducted the Jadad scoring,the basic situ-ation of each study and various observation indications (abdominal pain relief,time in bed,hospitalization du-ration,hospitalization expenses,postoperative CRP,postoperative complications) in the ERAT group and LA group were extracted respectively.The RevMan 5.3 software was used for conducting the statistical analysis. Results A total of 33 trials with a total of 2630 patients were included.There were 1294 cases in the ERAT group and 1336 cases in the LA group.The meta analysis results showed that the remission rate of abdominal pain at postoperative 12 h (RR=1.23,95％CI:1.06-1.43),time in bed (with d or h as the unit,WMD=-3.00,95％CI:-3.93 to-2.07;WMD=-9.51,95％CI:-16.12 to-2.90),hospitalization duration (WMD=-2.44,95％CI:-2.90 to-1.98),treatment costs (WMD=-3.00,95％CI:-5.34 to-0.67),postoperative CRP (WMD=-4.94,95％CI:-7.43 to-2.45) and postoperative complications incidence rate (RR=0.24,95％CI:0.18-0.32) had statistical difference between the two groups (P<0.05).Conclu-sion ERAT has more advantages than LA in treating fecalith incarceration appendicitis.