Objective To study the effect of Mycobacterium tuberculosis (Mtb) Pro-Pro-Glu-59 (PPE59) protein on the biological function of Mycobacterium smegmatis (Ms) and the regulation of host cell immune response. Methods PPE59 gene fragment was obtained by PCR amplification, cloned into pALACE, constructed into recombinant pALACE-PPE59 vector, and electro-transformed into Ms. Western blot was applied to analyse PPE59 expression and subcellular localization. The survival of Ms_Vec and Ms_PPE59 under low acid (pH=3 and pH=5) conditions and active surface pressure sodium dodecyl sulfate (SDS) conditions and their intracellular survival in macrophages were analyzed. ELISA was used to detect the cytokine (IL-1β, IL-6, IL-12, TNF-α and IL-10) expression levels of Ms_Vec and Ms_PPE59 infected macrophages. Results PPE59 protein localized to the cell wall of Ms can enhance the acid-resistance and anti-SDS effect of Ms, which is conducive to the survival of Ms in macrophages. PPE59 significantly decreased the secretion levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 and TNF-α), and promoted the secretion levels of anti-inflammatory cytokine (IL-10). Conclusion PPE59 enhances the survival ability of Ms under low acid and SDS pressure and promotes its intracellular survival by regulating the cytokine secretion levels.
Mycobacterium smegmatis/metabolism* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Bacterial Proteins/metabolism* ; Animals ; Mice ; Antigens, Bacterial/metabolism*

Objective: To gain an in depth understanding of the cognitive appraisal of middle school students with mental illness after experiencing childhood trauma, so as to provide a reference for the development of effective interventions. Methods: From March to September in 2023, 21 middle school students with childhood trauma experiences and mental illnesses were selected from outpatient and inpatient departments through purposive sampling in a tertiary grade A psychiatric hospital in Wuhan. Semistructured interviews were conducted and the seven steps of Colaizzi phenomenology were used to analyze the data and extract themes. Results: A total of 3 themes and 11 subthemes were extracted:insufficient awareness of childhood trauma (lack of selfawareness, lack of awareness of primary caregivers), multiple hurtful experiences after experiencing childhood trauma (complex negative affective experiences, multiple physical discomfort, pessimistic attitudes toward life, social impairment, and academic impairment), and influences on childhood trauma experiences (personality traits, inappropriate personal coping styles, poor upbringing environment, and difficulty in obtaining social support). Conclusions Middle school students with mental illnesses and their caregivers generally lack knowledge about childhood trauma, which brings widespread harm and are affected by multiple factors. It should jointly strengthen the popularization of scientific knowledge, intervene in a timely manner, and thereby reduce the adverse consequences of childhood trauma experiences.

Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.

OBJECTIVE: To investigate the effect of p-coumaric acid on apoptosis of multiple myeloma cells and its related mechanism. METHODS: Multiple myeloma cell line MM.1s cells were selected and treated with different concentrations of p-coumaric acid (0, 0.4, 0.8, 1.6, 3.2 mmol/L), and the inhibition rate and half inhibition concentration (IC₅₀) were detected by CCK-8 method. Then MM.1s cells were treated with 1/2 IC₅₀, IC₅₀, 2 IC₅₀ and transfected with ov-Nrf-2 and ov-Nrf-2+IC₅₀. The apoptosis, ROS fluorescence intensity and mitochondrial membrane potential of MM.1s cells were detected by flow cytometry, and the relative expressions of cellular Nrf-2 and HO-1 protein were detected by Western blot. RESULTS: P-coumaric acid inhibited the proliferation of MM.1s cells in a dose-dependent manner(r =0.997) with an IC₅₀ value of 2.754 mmol/L. Compared with the control group, apoptosis and ROS fluorescence intensity of MM.1s cells were significantly increased in the 1/2 IC₅₀ group, IC₅₀ group, 2 IC₅₀ group and ov-Nrf-2+IC₅₀ group (P <0.01), the expressions of Nrf-2, HO-1 protein in the IC₅₀ group and 2 IC₅₀ group were significantly decreased (P <0.05). Compared with the IC₅₀ group, the cells apoptosis and ROS fluorescence intensity were significantly decreased (P <0.01), and the expressions of Nrf-2 and HO-1 protein were significantly increased in the ov-Nrf-2+IC₅₀ group (P <0.01). CONCLUSION P-coumaric acid can inhibit the proliferation of MM.1s cells and may target the Nrf-2/HO-1 signaling pathway to affect oxidative stress in MM cells thereby inducing their apoptosis.
Humans ; Reactive Oxygen Species/pharmacology* ; Cell Line, Tumor ; Multiple Myeloma ; Oxidative Stress ; Apoptosis

OBJECTIVE: To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft. RESULTS: There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4⁺CD25⁺ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078). CONCLUSION High number of CD34⁺ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3⁺ cells, CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells, NK cells and CD14⁺ cells tend to increase the occurrence of aGVHD, but high number of CD4⁺CD25⁺ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; CD4-Positive T-Lymphocytes ; Leukemia, Myeloid, Acute/complications* ; Graft vs Host Disease

OBJECTIVE: To investigate the predictive value of complete blood count (CBC) and inflammation marker on the recurrence risk in children with Henoch-Schönlein purpura (HSP). METHODS: One hundred and thirty-three children with HSP admitted to Cangzhou Central Hospital from February 2017 to March 2019 were enrolled. The clinical data of the children were collected, at the time of admission CBC and C-reactive protein (CRP) were detected. After discharge, the children were followed up for 1 year, the clinical data of children with and without recurrence were compared, and multivariate logistic regression was used to analyze the risk factors affecting HSP recurrence. Receiver operating characteristic (ROC) curve should be drawn and the predictive value of CBC and CRP on HSP recurrence should be analyzed. RESULTS: In the follow-up of 133 children, 8 cases were lost and 39 cases recurred, with a recurrence rate of 31.20% (39/125). The age, skin rash duration, proportion of renal damage at the initial onset, percentage of neutrophils, percentage of lymphocytes, platelet count (PLT), mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/PLT ratio (MPR), and CRP level of patients with recurrence were statistically different from those without recurrence (P <0.05). Multivariate logistic regression analysis showed that long skin rash duration, renal damage at the initial onset, increased PLR, high PLT, increased MPV and elevated CRP level were independent risk factors for recurrence in children with HSP (P <0.05). The ROC curve analysis showed that the area under the curve (AUC) of the combination of the four blood and inflammation marker (PLT, MPV, PLR and CPR) in the early prediction of HSP recurrence was 0.898, which was higher than the initial renal damage (AUC=0.687) and persistent skin rash time (AUC=0.708), with a sensitivity of 84.62% and a specificity of 83.72%. CONCLUSION Observation of CBC and CPR can predict the risk of HSP recurrence early and guide early clinical intervention.
Humans ; Child ; IgA Vasculitis ; Blood Cell Count ; Inflammation ; C-Reactive Protein ; Lymphocytes ; Neutrophils ; Exanthema ; Retrospective Studies

OBJECTIVE: To investigate the correlation between ¹⁸Fluoro-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) metabolic parameters and peripheral blood circulating tumour DNA (ctDNA) in patients with diffuse large B-cell lymphoma (DLBCL), and the prognostic value of these two types of parameters in predicting progression-free survival (PFS). METHODS: Clinical, PET/CT and ctDNA data of DLBCL patients who underwent peripheral blood ctDNA testing and corresponding PET/CT scans during the same period were retrospectively analyzed. At the time of ctDNA sampling and PET scan, patients were divided into baseline and relapsed/refractory (R/R) groups according to different disease conditions. CtDNA mutation abundance was expressed as variant allele frequency (VAF), including maximum VAF (maxVAF) and mean VAF (meanVAF). Total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG) were obtained by the 41% maximum normalized uptake value method, and the distance between the two farthest lesions (Dmax) was used to assess the correlation between PET parameters and ctDNA mutation abundance using Spearman correlation analysis. The receiver operating characteristic (ROC) curves were used to obtain the optical cut-off values of those parameters in predicting PFS in the baseline and R/R groups, respectively. Survival curves were outlined using the Kaplan-Meier method and log-rank test was performed to compare survival differences. RESULTS: A total of 67 DLBCL patients ［28 males and 39 females, median age 56.0(46.0, 67.0) years］ were included and divided into baseline group (29 cases) and R/R group (38 cases). Among these PET parameters, baseline TMTV, TLG, and Dmax were significantly correlated with baseline ctDNA mutation abundance, except for maximum standardized uptake value (SUVmax) (maxVAF vs TMTV: r=0.711; maxVAF vs TLG: r=0.709; maxVAF vs Dmax: r=0.672; meanVAF vs TMTV: r=0.682; meanVAF vs TLG: r=0.677; meanVAF vs Dmax: r=0.646). While in all patients, these correlations became weaker significantly. Among R/R patients, only TMTV had a weak correlation with meanVAF (r=0.376). ROC analysis showed that, the specificity of TMTV, TLG and Dmax in predicting PFS was better than mutation abundance, while the sensitivity of ctDNA mutation abundance was better. Except R/R patients, TMTV, TLG, Dmax, and VAF were significantly different at normal/elevated lactate dehydrogenase in baseline group and all patients (all P<0.05). Survival curves indicated that high TMTV (>109.5 cm³), high TLG (>2 141.3), high Dmax (>33.1 cm) and high VAF (maxVAF>7.74%, meanVAF>4.39%) were risk factors for poor PFS in baseline patients, while only high VAF in R/R patients (both maxVAF and meanVAF >0.61%) was a risk factor for PFS. CONCLUSION PET-derived parameters correlate well with ctDNA mutation abundance, especially in baseline patients. VAF of ctDNA predicts PFS more sensitively than PET metabolic parameters, while PET metabolic tumour burden with better specificity. TMTV, TLG and VAF all have good prognostic value for PFS. PET/CT combined with ctDNA has potential for further studies in prognostic assessment and personalized treatment.
Male ; Female ; Humans ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Circulating Tumor DNA/genetics* ; Retrospective Studies ; Positron-Emission Tomography ; Survival Analysis ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; Prognosis

Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China was published in the British Journal of Clinical Pharmacology in February 2022. The guideline followed the latest definition of clinical practice guideline and the methodology specification for the guideline development of WHO. The Grading of Recommendations Assessment ， Development，and Evaluation （GRADE）approach was applied to rate the quality of evidence and determine the strength of recommendations. Finally ，this guideline presents 28 recommendations covering the whole process of clinical medication of high-dose methotrexate ，involving evaluation prior to administration （liver and renal function ，pleural effusion and ascites ， comedication，genetic testing ），pre-treatment and routine dosing regimen （pretreatment of hydration and alkalization ，urine alkalization，routine dosing regimen ），therapeutic drug monitoring （necessity，method，timing，target concentration ），leucovorin rescue（rescue timing ，rescue regimen ，rescue dose optimization ），and management of toxicities （liver and kidney function monitoring，supportive treatment ，blood purification treatment ）. This article aims to summarize and interpret the recommendations of this guideline ，so as to promote the better promotion and implementation of this guideline and provide comprehensive technical support and suggestions for whole-course individualized administration of high-dose methotrexate in China.

UNLABELLED: AbstractObjective: To analyze the expression of FOSB in acute myeloid leukemia （AML） and its correlation with prognosis of the patient based on the large sample data. METHODS: The genome, transcriptome, gene chip and clinical information from multiple public databases were statistical analyzed. RESULTS: The expression of FOSB gene in AML patients was significantly higher than that in normal people. The prognostic analysis of the 163 patients showed that the patients with high FOSB expression showed longer OS and EFS than those with FOSB low expression. The patients were further divided into chemotherapy group and allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the treatment method, and then each group was divided into two subgroups (FOSBhigh, FOSBlow) according to the median expression level of FOSB. In the allo-HSCT group, the patients with FOSB high expression was longer event-free survival (EFS: P=0.017) and overall survival (OS: P=0029). At the same time, allo-HSCT in patients with high FOSB expression could improve the prognosis of the patients (Chemotherapy vs Allo-HSCT, OS: P<0.001, EFS: P=0.007). Multivariate analysis showed that the high expression of FOSB was an independent favorable prognostic factor for EFS and OS (EFS: HR=0.501， P=0.019; OS: HR=0.461， P=0.009) of the patients. CONCLUSION The high expression of FOSB indicated a good prognosis for acute myeloid leukemia.
Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Multivariate Analysis ; Prognosis ; Proto-Oncogene Proteins c-fos/genetics*

OBJECTIVE: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis. METHODS: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient's initial diagnosis, the relationship between the patient's prognosis and CD47 was evaluated. RESULTS: The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34⁺, CD38⁺, CD123⁺ (P>0.05). The proportion of bone marrow protocells in AML patients was >50%, the ECOG score was >2 points, MLLELL fusion gene and chromosome prognosis stratification were all risk factors affecting the survival of patients (P=0023, 0.036, 0.012, 0.001, respectively). The high expression of bone marrow CD47 in AML patients indicated a high risk of recurrence (P=0.017). CONCLUSION The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.
Adult ; CD47 Antigen ; China ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Leukocytes, Mononuclear/pathology* ; Prognosis