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 investigate the clinical utility of krebs von den lungen-6(KL-6),a sialoglycan antigen,in the auxiliary diagnosis of idiopathic pulmonary hemosiderosis(IPH)in children.Methods A total of 140 children admitted to the First Affiliated Hospital of Guangzhou Medical University from June 2014 to July 2024 were categorized into a case group and a control group.The case group was further subdivided into four subgroups based on disease type:IPH group(n=32),interstitial lung disease(ILD)group(n=22),pneumonia(PN)group(n=60),and non-pulmonary disease(NPD)group(n=26).Serum KL-6 levels were measured for all children across these groups,and the differences in KL-6 expression between children with IPH and those without IPH(including the ILD,PN,and NPD groups)were analyzed.Results The positive rates of KL-6 in each group of children,from highest to lowest,were as follows:IPH(68.75%),ILD(45.45%),PN(1.69%),and NPD(0.00%).The differences in positive rates between groups were statistically significant(χ2=66.10,P<0.001).The mean serum level of KL-6 in the IPH group was significantly higher than that in the PN group(Z=-6.92,P<0.001).Diagnostic test results indicated that the area under the ROC curve was 0.940(95%CI:0.89 to 1.00,P<0.001),with a cut off value of 392.00 U/mL,sensitivity of 81.30%,and specificity of 95.00%.Conclusions KL-6 demonstrates significant diagnostic value in distinguishing IPH children from those with PN and NPD,making it a promising blood biomarker for aiding in the diagnosis of IPH.

AIM:To explore the correlation be-tween trimethylamine N-oxide(TMAO)and Hashi-moto's thyroiditis(HT)and to provide new ideas for early clinical diagnosis of HT.METHODS:A total of 102 patients with Hashimoto's thyroiditis(HT group)and 204 healthy individuals(control group)were included in the study and clinical data were collected.Serum TMAO levels was determined by stable isotope dilution high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).SPSS 26.0 was used for statistical analysis.RESULTS:Analysis of the baseline data revealed that there was a statistically significant difference between the TMAO levels and gender between the HT group and the control group(P<0.05).In the high-level TMAO group,the proportion of HT(63.7%)was significantly higher than that of the control group(18.6%),the regression analysis showed that high levels of TMAO were correlated with HT and positively correlated with the levels of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TgAb),Logistic regression analysis further revealed that serum TMAO was a risk factor for the development of HT.CONCLUSION:In the TMAO>6.80 μmol/L group,the level of TMAO was correlat-ed with HT,and the high level of TMAO was posi-tively correlated with TPOAb and TgAb,which were risk factors for the occurrence of HT.It is suggested that TMAO can predict the risk of HT and has cer-tain clinical value.

AIM:To explore the correlation be-tween trimethylamine N-oxide(TMAO)and Hashi-moto's thyroiditis(HT)and to provide new ideas for early clinical diagnosis of HT.METHODS:A total of 102 patients with Hashimoto's thyroiditis(HT group)and 204 healthy individuals(control group)were included in the study and clinical data were collected.Serum TMAO levels was determined by stable isotope dilution high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).SPSS 26.0 was used for statistical analysis.RESULTS:Analysis of the baseline data revealed that there was a statistically significant difference between the TMAO levels and gender between the HT group and the control group(P<0.05).In the high-level TMAO group,the proportion of HT(63.7%)was significantly higher than that of the control group(18.6%),the regression analysis showed that high levels of TMAO were correlated with HT and positively correlated with the levels of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TgAb),Logistic regression analysis further revealed that serum TMAO was a risk factor for the development of HT.CONCLUSION:In the TMAO>6.80 μmol/L group,the level of TMAO was correlat-ed with HT,and the high level of TMAO was posi-tively correlated with TPOAb and TgAb,which were risk factors for the occurrence of HT.It is suggested that TMAO can predict the risk of HT and has cer-tain clinical value.

Objective To investigate the clinical utility of krebs von den lungen-6(KL-6),a sialoglycan antigen,in the auxiliary diagnosis of idiopathic pulmonary hemosiderosis(IPH)in children.Methods A total of 140 children admitted to the First Affiliated Hospital of Guangzhou Medical University from June 2014 to July 2024 were categorized into a case group and a control group.The case group was further subdivided into four subgroups based on disease type:IPH group(n=32),interstitial lung disease(ILD)group(n=22),pneumonia(PN)group(n=60),and non-pulmonary disease(NPD)group(n=26).Serum KL-6 levels were measured for all children across these groups,and the differences in KL-6 expression between children with IPH and those without IPH(including the ILD,PN,and NPD groups)were analyzed.Results The positive rates of KL-6 in each group of children,from highest to lowest,were as follows:IPH(68.75%),ILD(45.45%),PN(1.69%),and NPD(0.00%).The differences in positive rates between groups were statistically significant(χ2=66.10,P<0.001).The mean serum level of KL-6 in the IPH group was significantly higher than that in the PN group(Z=-6.92,P<0.001).Diagnostic test results indicated that the area under the ROC curve was 0.940(95%CI:0.89 to 1.00,P<0.001),with a cut off value of 392.00 U/mL,sensitivity of 81.30%,and specificity of 95.00%.Conclusions KL-6 demonstrates significant diagnostic value in distinguishing IPH children from those with PN and NPD,making it a promising blood biomarker for aiding in the diagnosis of IPH.

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.

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.

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.

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.