OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: To explore the immunophenotypic characteristics of bone marrow granulocytes (G) and their clinical significance in patients with multiple myeloma (MM). METHODS: The granulocyte immunophenotypes of bone marrow in 70 MM patients (MM group) and 40 anemia patients (control group) were detected by flow cytometry, and its correlation with clinical characteristics was further analyzed. Univariate and multivariate regression analysis were used to screen factors that affected prognosis. RESULTS: The CD56⁺G%, CD13⁺G%, CD22⁺G% and CD117⁺G% in MM group were higher than those in the control group (all P <0.05). CD56⁺G% and CD117⁺G% in CR⁺VGPR group were significantly lower than those in PR+MR+PD group (both P <0.05). The CD10⁺G% in RISS Ⅲ stage and Ca²⁺ ≥2.65 mmol/L groups were increased (both P <0.05). The CD56⁺G% in elevated lactate dehydrogenase, β₂-microglobulin≥5.5 mg/L and hemoglobin <85 g/L groups were increased (all P <0.05), while the CD117⁺G% in high-risk cytogenetic positive group was decreased (P <0.05). The expression rate of CD molecules on granulocytes was divided into low (L) and high (H) groups according to the median value. The overall survival (OS) of the LCD56⁺G%, LCD13⁺G% and LCD22⁺G% groups was significantly prolonged (all P <0.05). CD13⁺G% and CD22⁺G% were independent risk factors for OS in MM patients (HR=0.443, 0.410, both P <0.05). CONCLUSION The CD56⁺G%, CD10⁺G% and CD117⁺G% are closely correlated with clinical features in MM patients, while CD13⁺G% and CD22⁺G% are closely correlated with prognosis. Detection of CD molecules expression on granulocytes may be used to evaluate prognosis and guide treatment.
Humans ; Multiple Myeloma/immunology* ; Granulocytes/immunology* ; Prognosis ; Immunophenotyping ; Male ; Bone Marrow ; Female ; Flow Cytometry ; Middle Aged ; Aged ; Clinical Relevance

OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant

OBJECTIVE: To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed. RESULTS: During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections. CONCLUSION The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Female ; Child ; Skin Diseases/etiology* ; Chronic Disease ; Transplantation, Homologous ; Male ; Child, Preschool ; Adolescent

OBJECTIVE To establish fingerprints and multi-components determination of Jieze lotion, and use chemometrics methods for quality evaluation. METHODS The HPLC-DAD fingerprints was established and 10 components were recognized by comparison with references. Meanwhile, their contents were determined. The data were evaluated by the methods of chemometrics such as similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis. RESULTS The similarity of 11 batches of Jieze lotion were all >0.95. The linearity was good(r≥0. 999 1) and the average recoveries were between 89.70% and 106.0% with the RSD of 1.52%−3.41%. Instrument precision, stability and reproducibility of the method were all great. The contents of the common ten components(gallic acid, protocatechuic acid, neochlorogenic acid, caftaricacid, 5-O-feruloylquinicacid, chlorogenic acid, phellodendrine chloride, magnoflorine, 4-O-feruloylquinic acid, berberinehydrochloride) were 40.103−55.841, 2.347−6.179, 8.336−23.810, 7.084−21.956, 33.098−53.833, 24.597−49.610, 21.587−31.188, 5.915−13.162, 115.381−189.702, 31.378−112.686 μg·mL−1, respectively. The results of chemometrics showed that the 11 batches of samples could be divided into 4 categories, and the strong characteristic peaks used to distinguish each batch of samples were berberine hydrochloride, 4-O-feruloylquinic acid, chlorogenic acid, neochlorogenic acid and 5-O-feruloylquinic acid. CONCLUSION The method is accurate and reliable, and it can be used for the quality control and comprehensive evaluation of Jieze lotion.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.

Objective To investigate the mechanism of the interaction between Wnt/β-catenin signaling and the epithelial mesenchymal transition(EMT)pathway in mediating sunitinib-resistance in renal cancer cells.Methods The sunitinib-resistant kidney cancer cell lines were constructed by stepwise increase in drug concentrations method with sunitinib,and were divided into resistance group,lv-NC group and lv-Twist group,and human kidney cancer cell lines were selected as normal group.The normal and drug-resistant groups were treated with conventional culture;the lv-NC group was treated with 40 μL of lv-NC lentivirus supernatant containing 2.25 × 108 TU·mL-1 for 72 h,and the lv-Twist group was treated with 50 μL of Twist lentivirus supernatant containing 1.64 × 108 TU·mL-1 for 72 h.The apoptosis ability was detected by flow cytometry;the cell migration ability was detected by cell scratch assay;the cell invasion ability was detected by Transwell assay;and the protein expression levels of Wnt1,β-catenin and Twist were detected by Western blotting assay.Results The apoptosis rates of control,resistant,lv-NC and lv-Twist groups were(17.60±0.59)％,(8.61±0.34)％,(8.60±0.40)％and(3.10±0.34)％;the migration rates were(14.10±0.12)％,(27.64±0.41)％,(14.24±0.45)％and(32.74±2.53)％;the number of invading cells was 27.33±1.15,53.33±1.53,46.00±2.65 and 99.33±2.52;the relative expression levels of Wnt1 protein were 0.10±0.01,0.96±0.06,0.39±0.03 and 3.09±0.31;the relative expression levels of β-catenin protein were 0.39±0.01,1.48±0.16,0.81±0.05 and 1.24±0.14;the relative expression levels of Twist protein were 0.10±0.02,0.91±0.04,0.39±0.03 and 3.09±0.31,respectively.The differences of above indexes were statistically significant between the resistant group and the normal group,and between the lv-Twist group and the lv-NC group(all P＜0.05).Conclusion Twist(EMT related protein)mediates sunitinib resistance in renal cell carcinoma by interacting with Wnt/β-catenin signaling pathway.

The development and change patterns as well as the disease course management of multiple ground-glass nodules(GGNs)in the lungs are currently hotspots and difficulties in clinical lung cancer research.Understanding the latest advancements in the natural history of multiple GGNs is crucial for grasping the disease variation patterns and formulat-ing management strategies.Meanwhile,utilizing advanced methods such as intelligent follow-up management platforms makes the long-term standardized management of GGNs possible.Therefore,this article provides an overview of the latest research advancements on the natural history of multiple GGNs and new experience in GGNs management.

Objective To search for the reports of adverse events of levofloxacin use in children using the FAERS database,and to mine and analyze the data to provide reference for safe clinical use.Methods The data reported of adverse events of levofloxacin use in children from January 1,2004 to June 30,2023 were retrieved through the OpenVigil 2.1 platform,and the relevant data were analyzed based on the reporting odds ratio(ROR)method.Results A total of 484 cases of adverse events of levofloxacin in children were retrieved,and 94 positive risk signals were found.The main systemic organs involved were various musculoskeletal and connective tissues,gastrointestinal system,systemic and administration sites,and the top five positive signals were Dimycodes infection(ROR=822.87),tendon pain(ROR=563.71),Mycobacterium ulcers infection(ROR=352.65),tendon rupture(ROR=341.91),and immune reconstitution inflammatory syndrome-related tuberculosis(ROR=310.84).The top five positive signals not mentioned in the label were Mycobacterium ulcerans infection(ROR=352.65),immune reconstitution inflammatory syndrome-associated tuberculosis(ROR=310.84),central nervous system tuberculoma(ROR=102.85),linear IgA disease(ROR=82.68),and increased intracranial pressure(ROR=32.46).Conclusion In addition to the known adverse events,levofloxacin is used in children,and the risk signal intensity of adverse reactions such as increased intracranial pressure and tuberculosis-related diseases is high,so it is recommended to carefully select and strengthen relevant safety monitoring.

This study aimed to investigate the effect of iron overload on the transplant outcomes of pediatric patients with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on the clinical data of 74 children with SAA who received allo-HSCT at the Hematology Department of Wuhan Children’s Hospital between January 2018 and August 2022. Children with iron overload (serum ferritin >1 000 μg/L) before transplantation had a longer disease course, received more red blood cell transfusions, and had a higher number of CD34 + cells infused. Moreover, iron overload significantly delayed the reconstitution of regulatory T cells after transplantation, increasing the incidence of hemorrhagic cystitis and grade Ⅲ-Ⅳ acute graft-versus-host disease after transplantation. However, iron overload did not significantly affect the overall survival and failure-free survival rates of the children.