Objective: To explore the effect of interferon regulatory factor 2 binding protein 2 ( IRF2BP2) on the proliferation of acute myeloid leukemia ( AML) cells and its molecular mechanism． Methods: The CRISPR-Cas9 gene editing technology was used to knock out IRF2BP2 in human AML cell lines Kasumi-1 and U937，and West- ern blot was performed to detect the knockout efficiency of IRF2BP2 protein．Cell morphology was observed using a microscope．Cell phenotypes were analyzed by CCK-8 assay，colony formation experiments，and flow cytometry． RNA-Seq was performed to identify differentially expressed genes between the IRF2BP2 knockout group and the control group in the U937 cell line．Gene Set Enrichment Analysis ( GSEA) was conducted to explore the down- stream molecular mechanisms．Western blot was used to detect the expression of downstream differentially expressed genes．The Cleavage Under Targets and Tagmentation ( CUT＆Tag) technique was applied to identify the direct tar- gets of the IRF2BP2 protein，and the corresponding binding signals were visualized using the Integrated Genomics Viewer ( IGV) ． Results: Compared with the control group，after knocking out IRF2BP2，the CCK-8 experiment showed that AML cell proliferation was inhibited ( P ＜0. 05) ; the number of colonies in the IRF2BP2 knockout group decreased ( P＜0. 05) ，and the proportion of G1 phase was prolonged ( P＜0. 05) ; in U937 cell lines，knoc- king out IRF2BP2 resulted in significant enrichment of differential genes in myelocytomatosis oncogene ( MYC) -re- lated signaling pathways，and the protein expression levels of pathway molecules MYC，cyclin-dependent kinase 4 ( CDK4) ，and cyclin － dependent kinase 2 ( CDK2 ) decreased with the downregulation of IRF2BP2; using IRF2BP2 antibodies in U937 cell lines for CUT＆Tag experiments，IGV visualization analysis showed a significant increase in signal peaks in the MYC promoter region． Conclusion IRF2BP2 protein affects the cell cycle and pro- liferation of AML cells by targeting and regulating MYC．

Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective:To evaluate the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in treating pediatric Diamond-Blackfan anemia (DBA).Method:Clinical data of five pediatric DBA recipients who underwent haplo-HSCT at the Children's Hospital of Soochow University between June 2018 and June 2023 were retrospectively analyzed. The conditioning regimen comprised a backbone protocol of fludarabine, busulfan, and rabbit anti-human thymocyte immunoglobulin (Bu+Flu+ATG), with optional cyclophosphamide, rituximab, or thiotepa. Post-transplant prophylaxis for graft-versus-host disease (GVHD) included cyclosporine A/tacrolimus combined with mycophenolate mofetil and methotrexate. Outcome measures included neutrophil and platelet engraftment times, hematopoietic reconstitution, incidence and severity of post-transplant complications, hemoglobin maintenance, and survival status. Literature was searched in CNKI, Wanfang, and PubMed using the keywords "Diamond-Blackfan anemia" "DBA" and "haplo-HSCT" in both English and Chinese.Result:The median age at transplantation was 61 months. Human leukocyte antigen (HLA) matching ranged from 5-8/10 loci. Stem cell sources included bone marrow alone (1 case), bone marrow plus peripheral blood stem cells (PBSCT, 2 cases), umbilical cord blood (CB-HSCT, 1 case), and PBSCT combined with CB-HSCT (1 case). All five recipients achieved successful engraftment with complete hematopoietic and immune reconstitution. Median neutrophil and platelet engraftment times were 11 days and 9 days, respectively, with erythroid reconstitution at 25 days post-transplant. Complications included grade IV acute GVHD (aGVHD) in one recipient, grade I aGVHD in two recipients, and chronic GVHD (cGVHD) in one recipient. Cytomegalovirus (CMV) infection occurred in three cases, and Epstein-Barr virus (EBV) infection in one case, all of which resolved with ganciclovir. No other transplant-related complications were reported. At a median follow-up of 44.8(4.8-59.2) months, all recipients were alive with sustained erythroid reconstitution and disease-free survival. Literature review (six studies) confirmed HSCT as an effective treatment for DBA, with prognosis closely related to age at transplantation, conditioning regimens, and donor selection.Conclusion:Haplo-HSCT can be considered as a viable treatment option for pediatric DBA recipients.

Objective:To investigate the correlation between preoperative calcitonin levels and upper mediastinal lymph node metastasis in medullary thyroid carcinoma (MTC).Methods:A retrospective analysis was conducted on 249 MTC patients who underwent surgery at the Cancer Hospital, Chinese Academy of Medical Sciences between January 2010 and December 2021. Based on postoperative pathology, patients were categorized into the upper mediastinal lymph node metastasis group ( n=41) and the non-upper mediastinal lymph node metastasis group ( n=208). Clinicopathological features were compared, and survival outcomes were assessed using Kaplan-Meier analysis. Receiver operating characteristic (ROC) curves were employed to determine the predictive efficacy and optimal cutoff value of preoperative calcitonin for the upper mediastinal lymph node metastasis group. Logistic regression identified independent risk factors for the upper mediastinal lymph node metastasis group. Results:Compared to the non-upper mediastinal lymph node metastasis group, the upper mediastinal lymph node metastasis group demonstrated a higher proportion of male patients, elevated levels of carcinoembryonic antigen and calcitonin, increased multifocality, larger primary tumor size, higher rates of extrathyroidal extension, advanced T and N stages, and greater incidences of lymph node metastasis and extracapsular invasion (all P＜0.01). Patients with upper mediastinal lymph node metastasis exhibited significantly lower overall survival than those without upper mediastinal lymph node metastasis ( P＜0.001). ROC curve analysis revealed an area under the curve of 0.783 for preoperative calcitonin in predicting upper mediastinal lymph node metastasis, with an optimal cutoff value of 1 865 pg/ml (sensitivity 71.79%, specificity 75.53%). Multivariate logistic regression analysis identified preoperative calcitonin levels >1 865 pg/ml ( OR=5.31, 95% CI: 1.77-15.94) and >15 metastatic lymph nodes ( OR=4.90, 95% CI: 1.87-12.89) as independent risk factors for the upper mediastinal lymph node metastasis group. Conclusions:Preoperative calcitonin＞1 865 pg/ml suggests a higher likelihood of MTC with upper mediastinal lymph node metastasis. For individuals with suspected upper mediastinal lymph node metastasis on imaging, combining preoperative calcitonin levels can reduce false-positive rates.

Objective:To explore the efficacy and feasibility of hypomethylating agent (HMA) as preventive therapy in children with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study. Data from 173 children who underwent allo-HSCT for high-risk AML at Children′s Hospital of Soochow University between August 2019 and April 2023 were analyzed. Participants were categorized into a trial group receiving HMA and a control group. Further classification was based on HMA courses:≥4 and <4 courses. The efficacy and safety of HMA preventive treatment after allo-HSCT were evaluated. Survival analysis was performed using the Kaplan-Meier method with Log-Rank testing, the Fine-Gray model was used to assess cumulative relapse rates and Cox regression was used to identify prognostic factors. Adverse events during HMA were descriptively analyzed.Results:Among 173 patients, there were 100 males (57.8%) and 73 females (42.2%), with the age of 81 (34,127) months. The starting time of HMA was 123 (91, 191) d post-transplant, continuing 4.0 (3.0, 6.5) courses and the follow-up period was 24 (13, 32) months. The trial group (53 cases) showed better 2-year overall survival (OS) rate ((88.6±5.6)% vs. (76.6±4.3)%, χ 2=5.00, P=0.025) and relapse-free survival (RFS) rate ((89.2±4.7)% vs. (56.2±4.8)%, χ 2=15.75, P<0.001) than control group (120 cases). The 2-year OS rates and RFS rates were similar between ≥4 courses group (31 cases) and <4 courses group (22 cases)(both P>0.05). The cumulative relapse rate in the trial group was significantly lower ((10.8±0.2)% vs. (35.2±0.2)%, χ 2=10.84, P=0.001) than control group. Among children with molecular relapse, 8 cases (8/30, 26.7%) in the control group had hematological relapse compared to 1 case (1/2) in the trial group ( χ 2=0.81, P=0.369). The differences in incidence of acute and chronic graft-versus-host disease (GVHD) were not statistically significant (all P>0.05). Cox regression analysis revealed that minimal residual disease (MRD) positivity detected by flow cytometry before allo-HSCT and chronic GVHD were independent risk factors for OS (both P<0.05).The HMA preventive treatment was an independent protective factor for RFS, while age ≥10 years and MRD positivity detected by PCR before allo-HSCT were independent risk factors for RFS (all P<0.05). In trial group, 38 cases experienced grade 3 to 4 adverse events (71.7%). Conclusion:HMA is safe as preventive treatment in post-transplant children with high-risk AML, which can reduce the relapse risk and doesn't increase the risk of GVHD.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To translate the European organization for research and treatment of cancer quality of life questionnaire-head and neck 43(EORTC QLQ-H&N43) and to conduct cultural debugging and reliability and validity testing for the Chinese version of the scale.Methods:The Chinese version of EORTC QLQ-H&N43 was formed through literal translation, integration, back translation, group discussion, cultural adjustment, and pre-investigation of the English version of the scale. From March 2023 to December 2023, convenience sampling was used to investigate 254 patients with head and neck tumors at the Cancer Hospital of the Chinese Academy of Medical Sciences, including 197 males and 57 females, aged (55.6±13.6) years. SPSS 25.0 statistical software was used to analyze the performance of the scale.Results:The Chinese version of EORTC QLQ-H&N43 retained all 43 items. After evaluation by 5 experts, the content validity index (I-CVI) at the item level of the scale ranged from 0.80 to 1.00, and the average content validity index (S-CVI/Ave) at the scale level was 0.991. Through exploratory factor analysis, a total of 9 common factors were extracted, with a cumulative variance contribution rate of 68.158%; Cronbach′s α coefficient of the total scale was 0.943, and the half reliability was 0.896.Conclusion:The Chinese version of EORTC QLQ-H&N43 has good reliability and validity, which can be used as an effective tool to evaluate the quality of life of head and neck cancer patients in China.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

An 8-year-old male child with acute lymphoblastic leukemia(ALL)developed signs of methotrexate(MTX)toxicity—such as vomiting,chest tightness,and rapidly elevated serum creatinine and uric acid levels—on the second day after his first high-dose methotrexate(HD-MTX)treatment.The toxicity is considered due to delayed excretion of methotrexate.The clinical pharmacist assisted the medical team in formulating a treatment plan that included adequate hydration and alkalinization,leucovorin rescue,and subsequent dose adjustment of MTX,based on therapeutic drug monitoring and pharmacogenetic testing results.By day 11,the patient's MTX plasma concentration,serum creatinine,and uric acid levels had returned to safe ranges.In this case,the clinical pharmacists used pharmaceutical knowledge to analyze potential factors contributing to delayed MTX elimination,and assisted the treatment team to improve the safety and efficacy of drug therapy.This case provides valuable experience for the standardized management of similar pediatric patients.

Objective:To investigate the clinical features, diagnosis and treatment of eso-phageal fistula (EF) after radiofrequency catheter ablation (RFCA) for atrial fibrillation.Methods:The retrospective and descriptive study was conducted. The clinical data of 15 patients with EF after RFCA for atrial fibrillation who were admitted to Beijing Anzhen Hospital of Capital Medical University from January 2020 to December 2024 were collected. There were 11 males and 4 females, aged (64±7)years. All patients underwent surgical treatment. Observation indicators: (1) diagnosis and surgery; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean±SD, measurement data with skewed distribution were represented as M (range), and count data were represented as absolute numbers. Results:(1) Diagnodid and surgery. Of the 15 patients, radiofrequency catheter ablation included pulmonary vein isolation plus linear ablation in 13 cases and pulmonary vein isolation alone in 2 cases. The time to postoperative symptom onset of EF in 15 patients was (13±8)days. The main clinical manifestations included persistent chest pain in 14 cases, fever in 12 cases, dysphagia in 2 cases, and neurological symptoms in 2 cases (the same patient could have multiple symptoms). All patients presented with signs of infection of varying severity. Contrast-enhanced chest computed tomography (CT) or pulmonary vein CT angio-graphy revealed mediastinal emphysema, pneumopericardium with pericardial effusion, localized esophageal wall thickening with exudation, abnormalities in the posterior wall of the left atrium, or contrast extravasation in all patients. Cerebral imaging examination showed newly developed cerebral infarcts in 2 patients. The time from symptom onset to surgical intervention was 2(range, 1-10)days.All 15 patients underwent surgical treatment immediately after being diagnosed or highly suspected of EF via multidisciplinary collaboration. Among them, 11 patients with atrial-esophageal fistula (AEF) underwent left atrial defect repair plus left thoracic esophageal repair under cardio-pulmonary bypass through a median sternotomy, 3 patients with simple EF underwent left thoracic esophageal repair, 1 patient with AEF underwent atrial repair plus esophageal exclusion and drainage due to severe mediastinal infection. The diameter of the left atrial defect in the 15 patients was (12±5)mm, and the diameter of the esophageal defect was (11±4)mm. There was no patient cured with conservative treatment or converted to surgical treatment after failed conservative treatment.(2)Postoperative situations.Of the 15 patients, 3 cases developed pulmonary infection and were improved after anti-infective treatment. The duration of postoperative hospital stay was (21±5)days. (3) Follow-up. All 15 patients were followed up for 11(range, 3-18)months. Two of 15 patients died. One patient undergoing atrial repair plus esophageal diversion and drainage died postoperatively due to sepsis and multiple organ failure, and one patient undergoing left thoracic esophageal repair died of acute cardiac tamponade one week after surgery. The remaining 13 patients recovered well, without recurrence or new complications.Conclusions:The main clinical features of esophageal fistula after RFCA for atrial fibrillation include persistent chest pain, fever, accompanying signs of infection. Early contrast-enhanced chest CT or pulmonary vein CT angiography is helpful for diagnosis, and active surgical treatment after confirmation via multidisciplinary collaboration can improve patient prognosis.