BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

Objective:To investigate the correlation between multifidus muscle cross-sectional area (CSA), fat infiltration index (FI), and the grading of lumbar facet joint degeneration (FJD).Methods:A retrospective analysis was conducted on the clinical data of 105 patients with lumbar FJD treated at Sichuan Orthopaedic Hospital between January 2015 and December 2020. Patients were divided into three groups according to the Weishaupt grading system: 37 cases with Weishaupt grade 1 (Mild Group), 44 cases with Weishaupt grade 2 (Moderate Group), and 24 cases with Weishaupt grade 3 (Severe Group). Baseline characteristics [sex, age, body mass index (BMI), treatment duration], pathological features at initial diagnosis [segmental distribution, bone mineral density (BMD) T-score, facet joint asymmetry, endplate morphology, Modic classification, Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score], and multifidus muscle MRI findings [multifidus cross-sectional area (CSA) and fat infiltration index (FI)] were compared among the three groups. The correlation between lumbar multifidus CSA, FI, and FJD grade was analyzed. Normally distributed measurement data were expressed as xˉ± s; comparisons among multiple groups were performed by one-way ANOVA, pairwise comparisons were performed by LSD- t tests. Counting data were expressed as case (%) and compared by χ2 test. Spearman correlation analysis was used to analyze the correlation between lumbar multifidus MRI parameters and FJD grade. Results:There were no statistically significant differences among the three FJD groups in sex, age, BMI, treatment duration, segmental distribution, BMD T-score, proportion of facet joint asymmetry, endplate morphology, Modic classification, ODI, or JOA score (all P>0.05). At the L4-5 level, the multifidus CSA on the affected side in the severe group was significantly smaller than in the moderate group and mild group [(6.2±1.2) cm2 vs. (7.0±1.1) cm2 vs. (7.8±1.2) cm2], and the CSA in the moderate group was smaller than in the mild group (all P<0.05). At both the L4-5 and L5-S1 levels, the FI on the affected side in the severe group was significantly greater than in the moderate group and mild group [(0.48±0.12) vs. (0.39±0.15) vs. (0.29±0.10) at L4-5; (0.49±0.12) vs. (0.41±0.10) vs. (0.30±0.13) at L5-S1], and the FI in the moderate group was greater than in the mild group (all P<0.05). Spearman correlation analysis showed that at the L4-5 level, multifidus CSA on the affected side was negatively correlated with FJD grade ( r=-0.41, P=0.004). At the L5-S1 level, FI on the affected side was positively correlated with FJD grade ( r=0.58, P<0.001). Conclusion:The CSA and FI of the multifidus muscle on the affected side in the lumbar spine exhibit significant correlations with the severity of FJD grading. Clinically, early functional exercises can be implemented based on the degree of multifidus muscle degeneration observed in patients.

Here we report the case of a CBF-AML patient with KIT p.D816V mutation who failed avapritinib induction therapy and subsequently underwent bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT), along with a literature review. The patient was a 64-year-old male who did not achieve remission after induction therapy with the DA regimen (Daunorubicin + Cytarabine). After reinduction with avapritinib combined with the DCHG regimen (Decitabine + Homoharringtonine + Cytarabine + Granulocyte colony-stimulating factor), he attained complete remission (CR) and flow cytometry minimal residual disease (MRD) negativity, but the RUNX1::RUNX1T1 fusion gene remained positive. During consolidation therapy, flow MRD reappeared, and the fusion gene level progressively increased. The patient then underwent a 9/10 HLA-matched unrelated donor allo-HSCT. Post-transplant, the fusion gene persisted, prompting treatment with the "ITI" regimen (with dose adjustments, including sequential addition of interferon and interleukin-2, pomalidomide incorporation, and standard vs. escalated dosing of "ITI" regimen). Currently, MRD negativity has been maintained for over 5 months, with good treatment tolerance. This finding suggest that the "ITI" regimen may serve as a novel and well-tolerated therapeutic option for CBF-AML patients with persistent RUNX1::RUNX1T1 fusion gene positivity after allo-HSCT and KIT p.D816V mutation, particularly in cases of avapritinib treatment failure.

Objective To assess the anti-skin photoaging properties of total flavonoids(TFT)extracted from the Chinese herb tulip,a preliminary analysis of its mechanism in combating skin photoaging were conducted.Methods UVB-induced photoaging mouse model was used to assess the anti-skin photoaging effects of TFT.A network pharmacology approach was used to conduct a preliminary analysis of TFT's mechanism of action against skin photoaging.Furthermore,molecular simulation was employed to predict the interactions between the active ingredients and target proteins.Results Treatment with TFT effectively improved skin condition in UVB-induced photoaging mice.The mechanism of action of TFT against skin photoaging likely involved the regulation of transcription factors such as NF-κB and AP-1,modulation of SASPs transcription,and inhibition of MMPs activity.Conclusion TFT is an effective anti-skin photoaging ingredient that deserves further research and development.

Objective:To evaluate the advantages and short-term clinical effects of totally robotic Nissen 360° fundoplication compared with laparoscopic surgery.Methods:A retrospective analysis was conducted on data of 110 patients undergoing Nissen 360° fundoplication at the Second Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University from Aug 2023 to Aug 2024. Among them, 50 cases underwent totally robotic fundoplication, and 60 cases underwent laparoscopic fundoplication. By comparing and analyzing the fatigue level of the primary surgeon during the operations, postoperative incisional pain in patients, swallowing function recovery and the time to resume a normal solid-food diet within 3 months post-surgery, the advantages of totally robotic surgery were evaluated. Additionally, by examining the postoperative recovery of reflux symptoms, postoperative patient comfort, and satisfaction levels in both groups, the short-term clinical outcomes of totally robotic surgery were assessed.Results:Both groups of patients successfully completed the surgeries without any intraoperative or postoperative complications occurring. The fatigue score of the primary surgeon in the totally robotic group was significantly better than that in the laparoscopic group[ (2.34±1.38) vs. (2.89±1.51), t=1.385, P<0.01]. The time taken to resume a normal solid-food diet postoperatively in the totally robotic group was significantly shorter than that in the laparoscopic group[ (27.90±6.77) d vs. (40.78±13.60) d, t =5.765, P<0.01]. Moreover, the postoperative pain comfort level was better in the robotic group than in the laparoscopic group [(1.65±0.72) points vs. (2.23±0.59) points, t=3.742, P<0.01]. Within 12 months postoperatively, the GERD-Q scores in the totally robotic group decreased significantly, and reflux symptoms disappeared, comparable to that in the laparoscopic group. Conclusions:The totally robotic Nissen 360° fundoplication leads to lower fatigue levels for the surgeon. Patients experience significant advantages in terms of postoperative pain perception and dietary recovery. Additionally, it demonstrates excellent postoperative anti-reflux efficacy, high patient comfort, and the surgery is safe and reliable.

Objective To investigate the damage mechanism of extracellular vesicles(EVs)derived from ves-tibular schwannoma(VS)on HEI-OC1 cells and the protective effect of the ferroptosis inhibitor ferrostatin-1(Fer-1).Methods Tumor tissues and clinical data were collected from four patients with stage Ⅱ or Ⅲ VS,classified as grade D according to the AAO-HNS hearing classification.Primary VS cells were extracted,and their conditioned supernatant was collected.EVs were isolated using ultracentrifugation and identified.HEI-OC1 cells were cultured in vitro and divided into three groups:the control group(no treatment),the EVs group(treated with 3000 parti-cles/cell VS-EVs for 24 hours),and the EVs+Fer-1 group(pretreated with 20 μmol/L Fer-1 for 2 hours followed by co-culture with 3000 particles/cell VS-EVs for 24 hours).Cell viability was assessed using the CCK-8 assay,re-active oxygen species(ROS)levels were quantified using the DCFH-DA fluorescent probe,and lipid peroxidation was evaluated using the BODIPY 581/591 C11 probe.Results Compared with the control group,the EVs group showed significantly reduced cell viability(P＜0.001)and increased levels of ROS(P＜0.001)and lipid peroxides(P＜0.001).However,the EVs+Fer-1 group exhibited significantly restored cell viability(P＜0.001)and re-duced levels of ROS and lipid peroxidation(P＜0.001).Conclusion VS-derived EVs disrupts redox homeostasis,promotes intracellular accumulation of lipid peroxides and ROS,and induces ferroptosis in HEI-OC1 cells.Fer-1 significantly alleviates VS-EVs-induced ferroptosis,thereby protecting HEI-OC1 cells from damage.

Objective To investigate the correlation between peripheral blood CD14+CD16+monocytes and IgG N-glycosyl levels and disease activity in patients with systemic lupus erythematosus(SLE).Methods A total of 109 SLE patients admitted to Xingtai Cental Hospital from August 2021 to November 2024 were retrospectively selected as the study objects.According to SLE disease activity index(SLE-DAI),the patients were divided into active group(n=52)and stable group(n=57).In addition,56 patients who underwent physical examination during the same period were selected as the control group.Clinical data of patients were collected,CD14+CD16+mononuclear cells were detected by flow cytometry(FCM),and IgG N-glycosyl levels were detected by hydrophilic interaction chromatography-mass spectrometry.Logistic regression analysis was performed to analyze the influencing factors of SLE-DAI,and multicollinearity test[variance inflation factor(VIF)]was performed for independent variables.The prediction model of disease activity was constructed.The effectiveness of the predictive model was evaluated by describing the recviver operator characteristic(ROC)curve and calculating the area under the curve(AUC)value.Hosmer-Lemeshow goodness-of-fit test predicted the calibration degree of the model.Results The levels of WBC,Hb,PLT,ALB,complement C3 and complement C4 in control group were higher than those in SLE group(t=8.917～22.171),and the levels of CRP were lower than those in SLE group(t=-17.359),with differences were statistical significance(all P<0.05).The CRP level and the proportion of CD14+CD16+mononuclear cells in the active group were higher than those in the stable group,and the differences were statistically significant(t=5.449,11.112,all P<0.05).The IgG glycosylation characteristics of galactosylation,sialylation and N-acetylglucosamine modification were lower than those in the stable group,and the differences were statistical significance(Z=-2.432～-0.158,all P<0.05).Spearman correlation analysis showed that the proportion of CD14+CD16+monocytes was significantly negatively correlated with IgG galactosylation,sialylation level and bisection N-acetylglucosamine modification(r=-0.656,-0.531,-0.608,all P<0.01).CD14+CD16+monocyte ratio was positively correlated with SLE-DIA(r=0.581,all P<0.01).IgG galactosylation,sialylation levels and bisection N-acetylglucosamine modification were negatively correlated with SLE-DIA(r=-0.645,-0.609,-0.503,all P<0.01).Logistic regression analysis showed that CRP>8.21mg/L,CD14+CD16+≥16.17%,sialylation<22.05%and isotropic N-acetylglucosamine modification<16.53%were independent risk factors for disease activity in SLE patients(Wald χ2=4.471～12.811,all P<0.05).The VIF values of the above independent variables were all less than 10.By establishing the Logistic regression prediction model and drawing the ROC curve,the AUC value for diagnosing SLE disease activity was 0.821(95%CI:0.733～0.905),the sensitivity,specificity and the Yodon index were 85.37%,75.67%,0.677,respectively.and the P values of Hosmer-Lemeshow goodness-of-fit test models were 0.568,respectively.Conclusion The proportion of CD14+CD16+monocytes in peripheral blood of SLE patients increase significantly,and the level of IgG glycosylation characteristics decrease,both of which are correlated with SLE-DIA.The predictive model constructed based on the two had a good ability to distinguish SLE-DIA from inactive state,with high sensitivity and moderate specificity conducive to early clinical recognition,and the model fitting effect is good.SLE-DIA can be evaluated more accurately.

During hospitalization in the ICU, rehabilitation exercises were recognized as a crucial method for enhancing patients′ quality of life, and the volume of exercise was shown to significantly influence the effectiveness of rehabilitation for ICU patients. This article reviews the definition of exercise volume in the context of ICU patient rehabilitation, the current status of reporting, its correlation with patient outcomes, and the available measurement tools. The aim is to provide a foundational reference for quantitative research on exercise rehabilitation in ICUs within our country.

Objective To assess the anti-skin photoaging properties of total flavonoids(TFT)extracted from the Chinese herb tulip,a preliminary analysis of its mechanism in combating skin photoaging were conducted.Methods UVB-induced photoaging mouse model was used to assess the anti-skin photoaging effects of TFT.A network pharmacology approach was used to conduct a preliminary analysis of TFT's mechanism of action against skin photoaging.Furthermore,molecular simulation was employed to predict the interactions between the active ingredients and target proteins.Results Treatment with TFT effectively improved skin condition in UVB-induced photoaging mice.The mechanism of action of TFT against skin photoaging likely involved the regulation of transcription factors such as NF-κB and AP-1,modulation of SASPs transcription,and inhibition of MMPs activity.Conclusion TFT is an effective anti-skin photoaging ingredient that deserves further research and development.

Objective To investigate the damage mechanism of extracellular vesicles(EVs)derived from ves-tibular schwannoma(VS)on HEI-OC1 cells and the protective effect of the ferroptosis inhibitor ferrostatin-1(Fer-1).Methods Tumor tissues and clinical data were collected from four patients with stage Ⅱ or Ⅲ VS,classified as grade D according to the AAO-HNS hearing classification.Primary VS cells were extracted,and their conditioned supernatant was collected.EVs were isolated using ultracentrifugation and identified.HEI-OC1 cells were cultured in vitro and divided into three groups:the control group(no treatment),the EVs group(treated with 3000 parti-cles/cell VS-EVs for 24 hours),and the EVs+Fer-1 group(pretreated with 20 μmol/L Fer-1 for 2 hours followed by co-culture with 3000 particles/cell VS-EVs for 24 hours).Cell viability was assessed using the CCK-8 assay,re-active oxygen species(ROS)levels were quantified using the DCFH-DA fluorescent probe,and lipid peroxidation was evaluated using the BODIPY 581/591 C11 probe.Results Compared with the control group,the EVs group showed significantly reduced cell viability(P＜0.001)and increased levels of ROS(P＜0.001)and lipid peroxides(P＜0.001).However,the EVs+Fer-1 group exhibited significantly restored cell viability(P＜0.001)and re-duced levels of ROS and lipid peroxidation(P＜0.001).Conclusion VS-derived EVs disrupts redox homeostasis,promotes intracellular accumulation of lipid peroxides and ROS,and induces ferroptosis in HEI-OC1 cells.Fer-1 significantly alleviates VS-EVs-induced ferroptosis,thereby protecting HEI-OC1 cells from damage.