Objective:This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD + R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods:The clinical data of 26 patients with FLT3-ITD + R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results:A total of 26 patients with FLT3-ITD + R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment ( P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion:The Gilt-based combination therapy is highly effective in treating FLT3-ITD + R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

Adult ; Humans ; Retrospective Studies ; Pneumonia ; Community-Acquired Infections/epidemiology* ; Hospitalization

Objective:To explore the disease-related impairment of functional and structural connectivity network and their relationship with psychometric hepatic encephalopathy score (PHES) in patients with chronic hepatitis B virus-related cirrhosis (HBV-RC) by combining resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI).Methods:Data of 30 HBV-RC patients [including 13 HBV-RC patients with minimal hepatic encephalopathy (MHE) and 17 HBV-RC patients without MHE (NMHE)] from April 2011 to October 2011 in Guangdong No.2 People′s Hospital were analyzed prospectively, and 38 healthy individuals matched for age, sex, and education with HBV-RC patients (HC group) were included during the same period. Rs-fMR and DTI data as well as PHES data of all participants were collected. Gretna and PANDA software package were used to preprocess the imaging data and construct the functional and structural network respectively. The network-based statistic (NBS) approach was used to compare the differences of the functional and structural connections among three groups. Spearman′s correlation analysis was used to identify the relationship between functional or structural connectivity and PHES. The structural equation modeling (SEM) was used to explore the relationships among functional connectivity, structural connectivity, and PHES.Results:Compared to HC group, both functional and structural connectivity in the whole brain progressively destroyed from NMHE to MHE, mainly involving cognitive control network, default mode network, and limbic network (NBS corrected, all P<0.01). There were significantly negative relationships between functional or structural connectivity and PHES in HBV-RC patients (false discovery rate corrected, all P<0.05). The SEM results showed the influence of structural connectivity on neurocognitive impairment was mediated by functional connectivity ( P<0.05). Conclusion:Both functional and structural networks progressively destroy in HBV-RC patients as the disease advanced and these alterations significantly correlate with PHES. Besides, the influence of structural connectivity on neurocognitive impairment is mediated by functional connectivity.

Objective:To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness.Methods:This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives.Results:30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day.Conclusions:Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

BACKGROUND: Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring. METHODS: Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting. RESULTS: There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment. CONCLUSIONS The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.
Animals ; Cytoskeletal Proteins/metabolism* ; Female ; Gene Expression Regulation ; Hippocampus/metabolism* ; Insulin-Like Growth Factor II/metabolism* ; Learning ; Learning Disabilities/psychology* ; Male ; Memory Disorders/psychology* ; Nerve Tissue Proteins/metabolism* ; Pregnancy ; Prenatal Exposure Delayed Effects/psychology* ; Random Allocation ; Rats ; Rats, Wistar ; Social Environment ; Stress, Psychological/genetics*

Objective:To compare the four nucleic acid detection method of hepatitis A virus.Methods:Using method A, B, and C real-time fluorescent quantitative RT-PCR(RT-qPCR)and method D droplet chip digital PCR(RT-dPCR)to detect the sensitivity of HAV plasmid and gradient dilution HAV vaccine respectively. Specific detection of related viral nucleic acid was performed. Methods A, B, and C were used to detect 40 artificially contaminated HAV oysters, commercially available oysters and serum samples, and HAV vaccine samples, and compare the detection rates. The recovery rates of method A and D on artificially contaminated oysters were compared with low concentration of HAV.Results:Both method A and B could detect HAV plasmids up to 10 copies/μL. In the detection of HAV vaccine with gradient dilution, the slope, R 2 value and amplification efficiency of method A, B, and C were all within the acceptable range (-3.446~-3.297, 0.991-0.998, -95.07%-101.051%). For 40 specimens from different sources, the positive detection rates of method A, B, and C were 50% (20/40), 47.5% (19/40), 55% (22/40), and the difference was not statistically significant ( χ2=0.467, P=0.792). Methods A and D have no significant difference in the detection sensitivity of gradient dilution vaccines. For the detection of artificially contaminated oysters with low concentration of HAV, the recovery rate of method D was higher than that of method A, but the difference was not statistically significant (F=0.294, P=0.642). Conclusions:There is no significant difference between method A, B, and C, which is more convenient and fast. When detecting low concentrations of HAV in food, Methods D had a slight advantage, but the detection cost is slightly higher. The detection method can be selected according to the actual situation.

Objective:To evaluate the prognostic significance of clonal gene mutations using next-generation sequencing in patients with core-binding factor acute myeloid leukemia (CBF-AML) who achieved first complete remission after induction chemotherapy.Methods:The study, which was conducted from July 2011 to August 2017 in First Affiliated Hospital of Soochow University, comprised 195 newly diagnosed patients with CBF-AML, including 190 patients who achieved first complete remission after induction chemotherapy. The cohort included 134 patients with RUNX1-RUNXIT1 + AML and 56 patients with CBFβ-MYH11 + AML. The cohort age ranged from 15 to 64 years, with a median follow-up of 43.6 months. Overall survival (OS) and disease-free survival (DFS) were assessed by the log-rank test, and the Cox proportional hazards regression model was used to determine the effects of clinical factors and genetic mutations on prognosis. Results:The most common genetic mutations were in KIT (47.6% ) , followed by NRAS (20.0% ) , FLT3 (18.4% ) , ASXL2 (14.3% ) , KRAS (10.7% ) , and ASXL1 (9.7% ) . The most common mutations involved genes affecting tyrosine kinase signaling (76.4% ) , followed by chromatin modifiers (29.7% ) . Among the patients receiving intensive consolidation therapy, the OS tended to be better in patients with CBFβ-MYH11 + AML than in those with RUNX1-RUNXIT1 + AML ( P=0.062) . Gene mutations related to chromatin modification, which were detected only in patients with RUNX1-RUNXIT1 + AML, did not affect DFS ( P=0.557) . The patients with mutations in genes regulating chromatin conformation who received allo-hematopoietic stem cell transplantation (allo-HSCT) achieved the best prognosis. Multivariate analysis identified KIT exon 17 mutations as an independent predictor of inferior DFS in patients with RUNX1-RUNXIT1 + AML ( P<0.001) , and allo-HSCT significantly prolonged DFS in these patients ( P=0.010) . Conclusions:KIT exon 17 mutations might indicate poor prognosis in patients with RUNX1-RUNXIT1 + AML. Allo-HSCT may improve prognosis in these patients, whereas allo-HSCT might also improve prognosis in patients with mutations in genes related to chromatin modifications.

Objective To compare the performance of three nucleic acid detection methods for hepatitis E virus.Methods The open reading frame (ORF) 2 gene sequence of HEV genotype 4 representative strain was cloned into pUC57 vector.Plasmid DNA was detected by two real-time quantitative method A and B,and the detection limits were compared.Other samples were used for specificity detection.Serum specimens of acute hepatitis E patients were detected by three method,and the results were compared.Results The lowest detection limit of plasmid DNA by A and B method can both reach 35 copies/reaction,with specificity of 100％.The HEV RNA positive rate of serum samples from acute hepatitis E patients by A,B and C method was 47.8％ (43/90),43.3％ (39/90) and 41.1％ (37/90),with the concordance rate of 88.9％ (80/90).There was no statistically significant difference among the three method (x2=0.8414,P=0.6566).Serum specimens with Ct values below 34.6 detected by method A,or below 35.6 detected by method B,the success rate of amplification by method C was 100％.Conclusions Method A has both higher sensitivity and specificity,and method C is a sensitive gene detection method.

Objective:This study aims to investigate the efficacy and safety of chimeric antigen receptor (CAR) T-cell bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of recurrent and refractory acute B-lymphocytic leukemia (R/R B-ALL) .Methods:A total of 50 R/R B-ALL patients who underwent CAR T-scell therapy to bridge allo-HSCT in the First Affiliated Hospital of Soochow University from January 2017 to May 2019 were retrospectively analyzed. The overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR) , and transplant-related mortality (TRM) of patients with different bone marrow minimal residual disease (MRD) levels were analyzed before and after CAR T-cell infusion and before allo-HSCT.Results:The response rate of CAR T-cell therapy and the incidence rate of severe cytokine release syndrome were 92% and 28% , respectively. During 55 infusions, no treatment-related deaths occurred in any of the patients. The median time of CAR T-cell infusion to allo-HSCT was 54 (26-232) days, the median follow-up time after CAR T-cell infusion was 637 (117-1097) days, and the 1-year OS and EFS rates were (80.0±5.7) % and (60.0±6.9) % . The 1-year CIR and TRM after allo-HSCT were (28.0±0.4) % and (8.0±0.2) % . After CAR T-cell infusion and before allo-HSCT, patients with bone marrow MRD<0.01% had a significantly longer EFS [ (70.0±7.2) % vs (20.0±12.6) % , P<0.001; (66.7±7.5) % vs (36.4±14.5) % , P=0.008]and lower CIR [ (25.0±0.5) % vs (70.0±2.6) % , P<0.001; (23.08±0.47) % vs (45.45±2.60) % , P=0.038]. Conclusion:CAR T-cell therapy bridging allo-HSCT is safe and effective for recurrent and refractory B-ALL.

Objective: To optimize the membrane filtration method for hepatitis A virus concentration from mimicked water samples. Methods: Mimicked water samples containing HAV particles were prepared and concentrated by positively charged membrane and negatively charged membrane respectively. Then different method including direct lysis, shaker, vortex and ultrasonication were used to elute HAV followed by the quantification of HAV by Taqman Real-time RT-PCR. The data were analyzed by professional statistical software. Results: In the present study, when mimicked water samples contained 300 TCID₅₀ of HAV, there was no significant difference between the concentration effects by negatively charged membrane and positively charged membrane (P=0.825>0.05). However, when HAV in mimic water samples was up to 1500 TCID₅₀ and 7500 TCID₅₀, the recycle efficiency by negatively charged membrane was higher than that by positively charged membrane (P<0.01). Additionally, this study found that HAV recycle ratio could be up to (68.17±16.79)% when direct lysis was used for viral elution, therefore direct lysis was proved much better than shaker, vortex and ultrasonication. They were significantly different (P<0.0001). Conclusions Elution process played the key role in HAV concentration when membrane filtration method was used. Direct lysis was proved much better than other method and it was the most efficient way in HAV recycle from mimicked water samples.