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.

Objective:To explore the clinical features of death in children with acute encephalopathy associated with influenza and corona virus disease 2019（COVID-19）and to enhance pediatrician's understanding of this disease.Methods:Clinical data of children with influenza and COVID-19-related acute encephalopathy hospitalized in Pediatric Intensive Care Unit of Children's Hospital Affiliated to Soochow University from September 2021 to July 2023 were retrospectively analyzed.The cases were divided into survival group and death group according to outcome.The general condition，clinical manifestations，auxiliary examination and treatment between the two groups were compared and analyzed.Results:A total of 41 pediatric patients were enrolled.In the death group,there were 17 cases,including 15 cases of acute necrotizing encephalopathy (ANE); among them,there were 7 male patients and 10 female patients,with a median age of 3.50 years.Eight patients were infected with influenza A virus,3 with influenza B virus,and 6 with SARS-CoV-2.The survival group comprised 24 cases,including 10 cases of ANE; among them,there were 16 male patients and 8 female patients,with a median age of 4.33 years.Fourteen patients were infected with influenza A virus,4 with influenza B virus,and 6 with SARS-CoV-2.None of the patients in the death group has received influenza and COVID-19 vaccines within 1 year before infection.Common symptoms were fever and disturbance of consciousness in the death group，eight cases had mild cough，seven cases had convulsions ≥three times，one case had two convulsions，nine cases had only one seizure，of which five cases were epileptic status.One case had delirium before convulsions.Seventeen cases began to fall into a coma (6.50±1.50) hours after their first onset of convulsion.Two patients had secondary pulmonary infection.Nine cases showed significantly elevated interleukin-6,while 17 cases had normal cerebrospinal fluid cell counts and 14 cases had elevated protein levels.All 17 cases underwent cranial CT scans,among which 13 showed symmetric necrosis of the bilateral thalami.All patients in the death group underwent glucocorticoid and intravenous immunoglobulin pulse therapy.Eleven patients received continuous renal replacement therapy,ten patients received intrathecal dexamethasone injection,and two patients were treated with tocilizumab.One patient underwent extracorporeal membrane oxygenation.Among the eight influenza patients,neuraminidase inhibitors were first administered 48 hours after the onset of fever.None of the six patients infected with SARS-CoV-2 received nirmatrelvir/ritonavir antiviral treatment.The causes of death in 17 patients included ANE(15 cases) and secondary infections(2 cases).Compared with the survival group,the incidence of brainstem involvement,shock,and low Glasgow coma scores (GCS ≤ 4) were significantly higher in the death group(15/17 vs.2/24， χ 2=26.18， P<0.001；16/17 vs.5/24， χ 2=21.39， P<0.001；14/17 vs.5/24， χ 2=15.15， P<0.001). Conclusion:Acute encephalopathy is primarily characterized by recurrent convulsions and disturbances of consciousness.Influenza and COVID-19 are the main causes.Cranial imaging is helpful for clinical diagnosis.Involvement of the brainstem,occurrence of shock,and GCS≤4 are associated with a higher fatality rate of ANE.

Transplantation-associated thrombotic microangiopathy（TA-TMA）is one of the severe complications after hematopoietic stem cell transplantation，and its specific pathogenesis has not yet been fully elucidated. In recent years，with in-depth research on TA-TMA，its pathogenesis has been gradually elucidated. It primarily involves multiple factors，including endothelial injury，aberrant activation of the complement system，and oxidative stress.Regarding treatment，in addition to conventional supportive therapy and etiology-directed management，various targeted therapies have emerged，including drugs like Eculizumab，recombinant thrombomodulin，defibrotide，and N-acetylcysteine.This article aims to systematically review the current research achievements and latest progress on the pathogenesis and treatment methods of TA-TMA，to provide references for the early prevention and treatment of TA-TMA.

Objective:To investigate the current use of ulinastatin in the treatment of critically ill children by pediatricians in China.Methods:A anonymous questionnaire survey was conducted among 147 pediatric critical care physicians from 36 hospitals across 16 provinces,autonomous regions,and municipalities in China.The survey content consists of three parts: respondents' basic information, the application status of ulinastatin, and the clinical indicators referenced for evaluating the use of ulinastatin. Descriptive statistical analysis was performed on the collected data.Results:Among the 147 respondents,99.32%(146/147) were from tertiary hospitals；72.11%(106/147) worked in specialized ICUs,and 4.08%(6/147)in emergency medicine departments.A total of 68.03%(100/147) of the physicians reported using ulinastatin in clinical practice.The main diseases for which ulinastatin was used were pancreatitis(26.40%),sepsis and septic shock(23.76%),capillary leak syndrome(21.78%),acute respiratory distress syndrome(8.91%),and disseminated intravascular coagulation(6.27%).A total of 90.00% of physicians combined ulinastatin with other medications,including glucocorticoids(26.82%),albumin(23.51%),plasma(17.22%),and immunoglobulins(13.58%). Clinical indicators referenced during ulinastatin use included elevated interleukin(IL)-6(76.87%),tumor necrosis factor-α(44.22%),IL-8(31.97%),IL-1(19.73%),IL-18(10.20%),blood lactate(59.18%),decreased serum albumin levels(70.07%),increased pleural or peritoneal effusion(67.35%),skin and mucosal edema(65.31%),and elevated thrombomodulin among the four coagulation parameters(58.50%).Conclusion:Ulinastatin is mainly used for the treatment of critical illnesses such as pancreatitis and sepsis.Most physicians combine ulinastatin with other drugs,such as glucocorticoids and albumin.Clinical indicators commonly referenced when using ulinastatin include elevated IL-6,increased lactate,and increased pleural effusion,which suggest a high inflammatory state and endothelial damage.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

Objective To explore the distribution characteristics and influencing factors of nasal colonized bacteria of healthcare workers(HCWs)in pediatric intensive care unit(PICU).Methods A cross-sectional study was con-ducted.Nasal swab specimens from 104 HCWs in the PICU of a hospital were collected for bacterial culture and an-timicrobial susceptibility testing.According to the identification and antimicrobial susceptibility testing results of strains,distribution characteristics of colonized bacteria was analyzed.Basic information of studied subjects were collected through questionnaire survey,and risk factors for colonized bacterial infection were conducted using logis-tic regression analysis.Results Among 104 specimens,colonized bacteria were detected from 66 specimens,with an overall detection rate of 63.46％.Gram-positive bacteria was mainly Staphylococcus aureus,with a detection rate of 34.62％(n=36),out of which methicillin-resistant Staphylococcus aureus(MRSA)accounted for 2.88％(n=3).Gram-negative bacteria was mainly Klebsiella spp.,with a detection rate of 21.15％(n=22).Multiva-riate logistic regression analysis showed that HCWs with junior professional titles(OR=11.400,95％CI:2.329-55.801,P=0.003)was an independent risk factor for Staphylococcus aureus colonization,and male(OR=4.260,95％CI:1.160-15.653,P=0.029)was an independent risk factor for Klebsiella spp.colonization.Conclusion Nasal cavity of HCWs in PICU has a high detection rate of colonized bacteria,with Staphylococcus aureus and Klebsiella spp.being the major colonized bacteria.

Objective:To explore the clinical features of death in children with acute encephalopathy associated with influenza and corona virus disease 2019（COVID-19）and to enhance pediatrician's understanding of this disease.Methods:Clinical data of children with influenza and COVID-19-related acute encephalopathy hospitalized in Pediatric Intensive Care Unit of Children's Hospital Affiliated to Soochow University from September 2021 to July 2023 were retrospectively analyzed.The cases were divided into survival group and death group according to outcome.The general condition，clinical manifestations，auxiliary examination and treatment between the two groups were compared and analyzed.Results:A total of 41 pediatric patients were enrolled.In the death group,there were 17 cases,including 15 cases of acute necrotizing encephalopathy (ANE); among them,there were 7 male patients and 10 female patients,with a median age of 3.50 years.Eight patients were infected with influenza A virus,3 with influenza B virus,and 6 with SARS-CoV-2.The survival group comprised 24 cases,including 10 cases of ANE; among them,there were 16 male patients and 8 female patients,with a median age of 4.33 years.Fourteen patients were infected with influenza A virus,4 with influenza B virus,and 6 with SARS-CoV-2.None of the patients in the death group has received influenza and COVID-19 vaccines within 1 year before infection.Common symptoms were fever and disturbance of consciousness in the death group，eight cases had mild cough，seven cases had convulsions ≥three times，one case had two convulsions，nine cases had only one seizure，of which five cases were epileptic status.One case had delirium before convulsions.Seventeen cases began to fall into a coma (6.50±1.50) hours after their first onset of convulsion.Two patients had secondary pulmonary infection.Nine cases showed significantly elevated interleukin-6,while 17 cases had normal cerebrospinal fluid cell counts and 14 cases had elevated protein levels.All 17 cases underwent cranial CT scans,among which 13 showed symmetric necrosis of the bilateral thalami.All patients in the death group underwent glucocorticoid and intravenous immunoglobulin pulse therapy.Eleven patients received continuous renal replacement therapy,ten patients received intrathecal dexamethasone injection,and two patients were treated with tocilizumab.One patient underwent extracorporeal membrane oxygenation.Among the eight influenza patients,neuraminidase inhibitors were first administered 48 hours after the onset of fever.None of the six patients infected with SARS-CoV-2 received nirmatrelvir/ritonavir antiviral treatment.The causes of death in 17 patients included ANE(15 cases) and secondary infections(2 cases).Compared with the survival group,the incidence of brainstem involvement,shock,and low Glasgow coma scores (GCS ≤ 4) were significantly higher in the death group(15/17 vs.2/24， χ 2=26.18， P<0.001；16/17 vs.5/24， χ 2=21.39， P<0.001；14/17 vs.5/24， χ 2=15.15， P<0.001). Conclusion:Acute encephalopathy is primarily characterized by recurrent convulsions and disturbances of consciousness.Influenza and COVID-19 are the main causes.Cranial imaging is helpful for clinical diagnosis.Involvement of the brainstem,occurrence of shock,and GCS≤4 are associated with a higher fatality rate of ANE.

Objective:To investigate the current use of ulinastatin in the treatment of critically ill children by pediatricians in China.Methods:A anonymous questionnaire survey was conducted among 147 pediatric critical care physicians from 36 hospitals across 16 provinces,autonomous regions,and municipalities in China.The survey content consists of three parts: respondents' basic information, the application status of ulinastatin, and the clinical indicators referenced for evaluating the use of ulinastatin. Descriptive statistical analysis was performed on the collected data.Results:Among the 147 respondents,99.32%(146/147) were from tertiary hospitals；72.11%(106/147) worked in specialized ICUs,and 4.08%(6/147)in emergency medicine departments.A total of 68.03%(100/147) of the physicians reported using ulinastatin in clinical practice.The main diseases for which ulinastatin was used were pancreatitis(26.40%),sepsis and septic shock(23.76%),capillary leak syndrome(21.78%),acute respiratory distress syndrome(8.91%),and disseminated intravascular coagulation(6.27%).A total of 90.00% of physicians combined ulinastatin with other medications,including glucocorticoids(26.82%),albumin(23.51%),plasma(17.22%),and immunoglobulins(13.58%). Clinical indicators referenced during ulinastatin use included elevated interleukin(IL)-6(76.87%),tumor necrosis factor-α(44.22%),IL-8(31.97%),IL-1(19.73%),IL-18(10.20%),blood lactate(59.18%),decreased serum albumin levels(70.07%),increased pleural or peritoneal effusion(67.35%),skin and mucosal edema(65.31%),and elevated thrombomodulin among the four coagulation parameters(58.50%).Conclusion:Ulinastatin is mainly used for the treatment of critical illnesses such as pancreatitis and sepsis.Most physicians combine ulinastatin with other drugs,such as glucocorticoids and albumin.Clinical indicators commonly referenced when using ulinastatin include elevated IL-6,increased lactate,and increased pleural effusion,which suggest a high inflammatory state and endothelial damage.

Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.

Objective:To understand the epidemiology, clinical characteristics and associated risk factors of severe adenovirus(ADV)pneumonia in children, providing the basis for targeted prevention and treatment.Methods:Clinical features of children with ADV pneumonia at Children′s Hospital of Soochow University from January 2011 to December 2020 were retrospectively analyzed.According to the severity of the disease, cases were divided into severe ADV pneumonia group and common ADV pneumonia group.The epidemiological and clinical characteristics of two groups were compared, and risk factors for the occurrence of severe ADV pneumonia were analyzed.Results:A total of 1 158 patients with ADV pneumonia were enrolled, including severe ADV pneumonia 104 cases(8.98%) and ordinary ADV pneumonia 1 054 cases(91.02%).The median age of severe ADV pneumonia group was 1.17 (0.83, 2.73) years, which was significantly younger than that of common ADV pneumonia group 3.16 (1.50, 4.50) years( P<0.05), and 77.89% (81/104) of them were younger than 3 years old.The occurrence of severe ADV pneumonia was predominant in winter and spring, accounting for 71.15% (74/104).Cough was present in 89.42% (93/104) and fever in 99.01% (103/104) of the severe ADV pneumonia group.Compared with the common ADV pneumonia group, the severe ADV pneumonia group had a significantly longer febrile time[10(6, 14)d vs. 5(4, 7)d, P<0.05], significantly higher incidence of shortness of breath, wheezing, convulsions/coma[100% vs. 2.09%, 45.19% vs. 13.57%, 10.57% vs. 1.99%, P<0.05], and significantly higher incidences of emphysema, pleural effusion, bronchial signs, pulmonary solids, and atelectasis [21.15% vs. 2.09%, 5.77% vs. 0.19%, 4.81% vs. 0, 3.85% vs. 0.09%, P<0.05].Multivariable Logistic regression showed that age younger than 1.71 years old, wheezing, and the presence of underlying diseases (moderate to severe anaemia, congenital heart disease, neurological disease) were risk factors for the development of severe ADV pneumonia ( P<0.05).Receiver operating characteristic curve analysis showed that the sensitivity and specificity of age<1.71 years old(20 months old) for predicting the occurrence of severe ADV pneumonia were 65.4% and 71.5%, respectively. Conclusion:The age of most severe ADV pneumonia is less 3 years in Suzhou.It usually occurres in winter and spring, with fever, cough, shortness of breath, and wheezing as the main symptoms.Pulmonary manifestations such as pleural effusion, emphysema, pulmonary consolidation, and atelectasis may occur.The underlying disease, wheezing, and age of onset less than 1.71 years (20 months) old are independent risk factors for severe ADV pneumonia.