Objective:To investigate effective strategies to reduce the high risk of recurrence after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with minimal residual disease(MRD)-positive B-lineage acute lymphoblastic leukemia(B-ALL).Methods:A retrospective analysis was performed for ten B-ALL patients with positive MRD before transplantation at our center from November 2022 to November 2024.There were four male patients and six female patients,with a median age of 30(7-56)years.Of all patients,four received transplantation from unrelated donors,and six received haploidentical transplantation from relatives.All ten patients received blinatumomab(28 μg/day for 14 days for patients≥45 kg;5 μg/m2/day for 14 days for patients<45 kg)and were bridged to the conditioning regimen for allo-HSCT within 7 days.Results:After treatment with blinatumomab,all ten patients achieved the clearance of MRD.After allo-HSCT,100%of the patients achieved donor hematopoietic reconstitution.The median time to neutrophil reconstitution was 12(9-22)days,and the median time to platelet reconstitution was 13.5(9-22)days.As of January 2025,the median observation time was 14(2-26)months;of all patients,two experienced recurrence,and one had positive MRD again,with a recurrence rate of 20%.Among the ten patients,nine survived and one died of disease recurrence.One patient achieved complete re-mission again after chimeric antigen receptor T-cell(CAR-T)therapy following recurrence,and the patient with positive MRD achieved the clearance of MRD again after interleukin-2 treatment;both patients were currently alive.During treatment,one patient developed cytokine release syndrome,one patient was comorbid with SARS-CoV-2 infection,one patient had herpes zoster and viral encephalitis,three patients developed grade Ⅰ-Ⅱ acute graft-versus-host disease,and four patients developed chronic graft-versus-host disease;no transplantation-associated thrombotic microangiopathy was observed.Conclusion:For patients with MRD-positive B-ALL,blinatumomab as a bridge therapy for allo-HSCT can significantly reduce recurrence after transplantation,with fewer complica-tions that are easy to control.Multicenter randomized controlled clinical studies can be performed to further verify its efficacy and safety.

Objective:To study the feasibility of magnetic resonance imaging(MRI)technique with amide proton transfer(APT)in predicting the prognosis of cerebral stroke.Methods:A total of 71 patients with acute cerebral stroke who admitted to the Nanjing First Hospital,Nanjing Medical University from September 2022 to May 2023 were selected.All of them underwent the test of National Institute of Health Stroke Scale(NIHSS),and received the MRI examination with chemical exchange saturation transfer(CEST).According to the modified Rankin scale(mRS)values of 1-month follow-up,they were divided into favorable recovery group(mRS<2,44 cases)and poor group(mRS≥2,27 cases).The asymmetric magnetization transfer ratio(MTRasym)image(APT)was obtained by analyzing data with special software.And then,the difference(△APTw)of APT values between ischemic zone and contralateral normal tissue was further calculated.The △APTw values of two groups were compared and analyzed,and the Pearson correlation analysis was adopted to analyze the correlation among △APTw,NIHSS and mRS.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of ROC curve was calculated.Results:There were significant positive correlations among △APTw,NIHSS and mRS scores(R2=0.659,0.522,P<0.001),and the differences of △APTW,NIHSS and mRS scores between the favorable recovery group and poor group were significant(t=5.73,6.36,13.92,P<0.05),respectively.The AUC value was 0.886,and the sensitivity and specificity of prediction were respectively 77.8%and 95.5%.The positive and negative predictive values were respectively 91.3%and 87.5%.Conclusion:APT imaging technique has feasibility in predicting the prognosis of acute cerebral ischemic stroke.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

Evidence-based medicine (EBM) is a science that uses the best available research data to make decisions, and the core is that clinical decision-making is supported by the best research evidence. Incorporating EBM into traditional standardized residency training in hematology can foster residents' professional theoretical knowledge and clinical skills, improve the quality of standardized training, and provide ideas and methods for standardized training of hematology residents, which is worthy of further research and exploration.

Purpose: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Methods: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Results: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. Conclusions This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

Objective To investigate the mechanical responses of mitochondrial morphology to extracellular matrix stiffness in human mesenchymal stem cells(hMSCs)and the role of AMP-activated protein kinase(AMPK)in the regulation of mitochondrial mechanoresponses.Methods Two polyacrylamide(PAAm)hydrogels,a soft one with a Young's modulus of 1 kPa and a stiff one of 20 kPa,were prepared by changing the monomer concentrations of acrylamide and bis-acrylamide.Then,hMSCs were cultured on the soft and stiff PAAm hydrogels and changes in mitochondrial morphology were observed using a laser confocal microscope.Western blot was performed to determine the expression and activation of AMPK,a protein associated with mitochondrial homeostasis.Furthermore,the activation of AMPK was regulated on the soft and stiff matrixes by AMPK activator A-769662 and the inhibitor Compound C,respectively,to observe the morphological changes of mitochondria.Results The morphology of the mitochondria in hMSCs showed heterogeneity when there was a change in gel stiffness.On the 1 kPa soft matrix,74%mitochondria exhibited a dense,elongated filamentous network structure,while on the 20 kPa stiff matrix,up to 63.3%mitochondria were fragmented or punctate and were sparsely distributed.Western blot results revealed that the phosphorylated AMPK(p-AMPK)/AMPK ratio on the stiff matrix was 1.6 times as high as that on the soft one.Immunofluorescence assay results revealed that the expression of p-AMPK was elevated on the hard matrix and showed nuclear localization,which indicated that the activation of intracellular AMPK increased continuously along with the increase in extracellular matrix stiffness.When the hMSCs on the soft matrix were treated with A-769662,an AMPK activator,the mitochondria transitioned from a filamentous network morphology to a fragmented morphology,with the ratio of filamentous network decreasing from 74%to 9.5%.Additionally,AMPK inhibition with Compound C promoted mitochondrial fusion on the stiff matrix and significantly reduced the generation of punctate mitochondria.Conclusion Extracellular matrix stiffness regulates mitochondrial morphology in hMSCs through the activation of AMPK.Stiff matrix promotes the AMPK activation,resulting in mitochondrial fission and the subsequent fragmentation of mitochondria.The impact of matrix stiffness on mitochondrial morphology can be reversed by altering the level of AMPK phosphorylation.

Objective To evaluate the value of magnetic resonance imaging (MRI) in screening for prostate cancer. Methods A total of 120 patients with a confirmed diagnosis of prostate cancer were enrolled in Nanjing Municipal First Hospital from March 2020 to March 2023, and 100 age-matched health volunteers during the study period served as controls. All patients and healthy individuals received prostate MRI scanning, and apparent diffusion coefficient (ADC) was estimated. Post-surgical pathology was used as a gold standard to evaluate the sensitivity and specificity of MRI in screening for prostate cancer. The correlation between pathological staging and ADC values in prostate cancer patients was investigated using Spearman correlation analysis. Results The mean ADC values were (1.01 ± 0.15) × 10⁻³, (0.88 ± 0.21) × 10⁻³, (0.72 ± 0.11) × 10⁻³, and (0.59 ± 0.09) × 10⁻³ mm²/s, respectively, for stage A, B, C, and D prostate cancer patients, and the differences were significant (F = 38.99, P < 0.01).Pearson correlation analysis showed a significant negative correlation between pathological staging and ADC value (r = −0.81, P < 0.05). In addition, the sensitivity and specificity of MRI in prostate cancer screening were 92.50% and 91.00%, respectively. Conclusion MRI shows a high value in screening for prostate cancer, and the ADC value is of great significance for staging prostate cancer.

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.
Humans ; Fecal Microbiota Transplantation ; Complement C3 ; Convalescence ; Prospective Studies ; Feces

Linarin, as a natural coumponent belongs to flavonoid glycoside, is widely existed in herbal plants such as chrysanthemum indicum and Mongolian flower, which has a variety of pharmacological effects, such as anti-inflammation, anti-cancer, liver protection, analgesia, antipyretic, anti-oxidation, anti-apoptosis, sedation and sleep, neuroprotection, preventing and treating hypertension, treatingdiabetes, preventing and treating osteoporosis, whitening, skin care and sunscreen. It is difficult to dissolve in water and has poor oral efficacy, but when combined with different substances or combined (forming phospholipid complex), its bioavailability can be improved, so as to improve its pharmacological efficacy.

Objective:To explore the clinical effect of the integrated model of doctors, nurses and patients in postoperative pain nursing of patients with osteosarcoma.Methods:A total of 20 patients with osteosarcoma who underwent surgical treatment in the Department of Orthopedics of Henan Provincial People's Hospital from June 2018 to June 2019 were selected as control group, and 20 patients with osteosarcoma surgery from July 2019 to July 2020 were selected as observation group. Control group was given routine nursing, and observation group carried out the integrated nursing of doctors, nurses and patients. One day before discharge, the Satisfaction Questionnaire on Postoperative Pain Management by the Patient and the limb salvage surgery efficacy scoring system (Musculoskeletal Tumor Society, MSTS) were distributed to patients to compare patients' satisfaction with postoperative pain management, pain status and limb function between two groups.Results:The hospital stay of control group was (45.63±8.56) d, and that of observation group was (36.78±7.69) d, the difference was statistically significant ( t=7.868, P<0.01) . The most severe postoperative pain score of observation group was (3.94±1.29) , which was lower than that of control group, and the difference was statistically significant ( t=4.458, P<0.01) . The satisfaction score of observation group for the pain effect was (4.11±0.64) , which was higher than that of control group, and the difference was statistically significant ( t=4.921, P<0.05) . The total score of MSTS in observation group was (25.98±2.15) , and that of control group was (20.54±2.08) , and the difference was statistically significant ( t=8.132, P<0.01) . Conclusions:The integrated model of doctors, nurses and patients can improve the satisfaction of perioperative pain management of patients with osteosarcoma, reduce the level of pain, and improve the level of limb function of patients.