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 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.

Objective:To investigate the clinical significance and possible mechanisms of elevated homocysteine(Hcy) levels in peripheral blood of children with sepsis.Methods:The clinical data of 51 children with sepsis (sepsis group) admitted to PICU at Xuzhou Children′s Hospital from January 2019 to December 2019 were analyzed, and the levels of Hcy in plasma were compared with 50 non-septic children (common infection group) and 50 healthy children (healthy control group) during the same period.The possible mechanism of metabolic disorders about Hcy was analyzed by detecting the levels of the key rate-limiting enzymes cystathionine-β-synthase(CBS) and cystathionine-γ-lyase(CSE), which were in the downstream of metabolism in septic mouse model induced by lipopolysaccharide.Results:The level of Hcy in plasma was (12.62±5.46)μmol/L in sepsis group, which was significantly higher than those in common infection group[(9.42±2.28) μmol/L] and healthy control group[(8.14±1.60) μmol/L]( P<0.05). The level of Hcy in plasma of 12 children with acute kidney injury in sepsis group was significantly higher than that of 39 children without acute kidney injury in sepsis group[(16.48±5.87)μmol/L vs.(11.62±4.74) μmol/L, P<0.05]. The level of Hcy in plasma of six children with acute liver failure in sepsis group was significant higher than that of 45 children without acute liver failure in sepsis group[(18.35±7.10) μmol/L vs.(11.84±4.78) μmol/L, P<0.05]. The level of Hcy in serum significantly increased in septic mouse models ( P<0.01). The transcription and protein expression levels of key rate-limiting Hcy transcription enzymes CBS and CSE in liver and kidney tissues of septic mouse were significantly down-regulated ( P<0.05). Conclusion:The level of Hcy in peripheral blood of children with sepsis increases, which is more obviously in children with acute kidney injury or acute liver injury.When patients developed sepsis, the expression of CBS and CSE will be restrained, leading to disorders related to transsulfuration metabolism and elevated level of Hcy in peripheral blood.

Objective:To clarify the clinical characteristics and related fators of children with delayed antibody production of mycoplasma pneumoniae pneumonia(MPP).Methods:Two hundreds and eithty-five cases of children hospitalized at Children′s Hospital of Soochow University with MPP(positive for nucleic acid testing of respiratory secretion)were chosen from January 1st, 2019 to September 31st, 2019.Delayed antibody production group included 36 cases, who were tested for negative IgM antibody meanwhile the titer of IgG antibody changed less than 4 folds within 14 days.Positive group included 249 cases who were tested for positive IgM antibody or the titer of IgG antibody changed over 4 folds within 14 days.The characteristics of clinical manifestation, immunology and radiology were comparatively analyzed.Results:The medium age of delayed antibody production group was 0.75(0.30, 2.78)years old, which was obviously younger than that from positive group[5.50(3.73, 7.20)years old]( P<0.001). Low level of serum immunoglobulin IgG was the independent effect factor of delayed production for Mycoplasma pneumoniae antibody( P=0.037). When the serum immunoglobulin IgG level was lower than 7.155mmol/L, the sensitivity of predicting delayed production for mycoplasma pneumoniae antibody would be 0.819 and the specificity was 0.833.The underlying diseases associated with delayed antibody production were hospitalization history during neonatal period( P=0.007)and congenital heart disease( P=0.001). There were 11.11%(4/36)of children appearing spasmodic cough, 41.67%(15/36)of children showing wheezing and 33.33%(12/36)showing diarrhea in delayed antibody group, which were significantly higher than those in positive group[0.40%(1/249), 24.50%(61/249)and 9.64%(24/249), respectively, P<0.05]. The incidence of fever in delayed antibody group were 63.89%(23/36), which was lower than that in positive group[92.37%(230/249)]( P<0.001), meanwhile, the fever last time was 2.50(0, 4.75)days in delayed antibody group, which was shorter than that in positive group[ 7(5.00, 8.50)days]( P<0.001). In the delayed antibody group, there was 19.44%(7/36)of children sufferring from lobar pneumonia, and no extrapulmonary manifestations occurred, which were significantly lower than those in positive group[75.50%(188/249), 14.86%(37/249)]( P<0.05). Conclusion:Delayed antibody production in children with MPP is more common when serum immunoglobulin IgG level is lower than 7.155 mmol/L, especially in the presence of neonatal hospital history and congenital heart disease.The clinical manifestations of these children are mainly characterized by spasmodic cough and wheezing, with low probability of fever, lobular pneumonia and extrapulmonary manifestations.

Abnormal transcription of oncogenes driven by super enhancers was found to be critical for maintaining tumor cell identity.The expression of oncogenes can be effectively suppressed by inhibiting the key regulator that super enhancers regulate oncogene transcription.Bromodomain protein 4(BRD4)is a key protein to recognize the super enhancer regulatory elements, which can bind to acetylated histones or non-histones to regulate gene transcription.The abnormal expression of BRD4 is closely related to the malignant development of a variety of hematologic oncology.Targeting BRD4 can effectively control the malignant development of hematologic tumors.In recent years, BRD4-targeted drugs in hematologic oncology have received extensive attention, and they showed good antitumor effects either as a single drug or in combination with other drugs.In this paper, in order to provide a new understanding of the occurrence of leukemia and treatment of hematologic oncology, the biological functions of BRD4 as well as the molecular drugs targeting BRD4 are reviewed.

Objective:To study the pathogenic distribution of bronchoalveolar lavage fluid in children with severe pneumonia from Children′s Hospital Affiliated to Soochow University, and to investigate the drug resistance of major pathogenic bacteria.Methods:A total of 177 children with severe pneumonia undergoing fiberoptic bronchoscopy in Children′s Hospital Affiliated to Soochow University from January 2014 to December 2018 were enrolled.Their bronchoalveolar lavage fluid was collected for pathogen identification, pathogen culture and drug sensitivity analysis.The pathogens were detected by direct immunofluorescence quantitative PCR.Results:Of 177 cases enrolled, 100 children had at least one pathogen detected, and the positive rate was 58.13%.Among all the pathogens detected, Mycoplasma pneumonia (MP) had the highest detection rate, which was found in 41 cases.The top three bacteria detected included Streptococcus pneumoniae (9 cases, 10.59%), Staphylococcus aureus (8 cases, 9.41%), and Pseudomonas aeruginosa (6 cases, 7.06%). The top three viruses detected were cytomegalo virus (CMV) (14 cases, 33.33%), human bocavirus (HBoV) (10 cases, 23.81%), and respiratory syncytial virus (RSV) (8 cases, 19.05%). The drug sensitive test indicated that main kinds of Gram-negative bacteria had low resistance to quinolones, aminoglycosides, carbapenems, and enzymatic beta-lactams.Main kinds of Gram-positive bacteria had low resistance to Linezolid and vancomycin.The virus detection rate and MP detection rate in severe pneumonia children under 5 years old were about 30.00% and 20.00%, respectively.The MP detection rate in children above 5 years old exceeded 30.00%.The bacteria detection rates in children under and above 2 years old were over 20.00% and about 15.00%, respectively.Airway abnormalities were common in children with severe pneumonia, mainly including tracheobronchial malacia and stenosis. Conclusions:The most common pathogen of bronchoalveolar lavage fluid in severe pneumonia children under 5 years old in Suzhou is viruses.The bacteria detection rate is high in children under 2 years old.Common Gram-positive bacteria show high susceptibility to vancomycin and Linezolid. Pseudomonas aeruginosa is highly sensitive to quinolones, aminoglycosides, carbapenems, and enzymatic beta-lactams.Importance should be attached to the airway abnormalities in children, especially infants, with severe pneumonia.

Phosphoglycerate dehydrogenase (phosphoglycerate dehydrogenase,PHGDH) encodes 3-phosphoglycerate dehydrogenase,the first enzyme branching from glycolysis in the serine biosynthetic pathway.PHGDH uses NAD as a cofactor to oxidizes glycolytic intermediate,3-phosphoglycerate,into phosphor-hydroxypyruvate,which then convert into serine by a series of enzymes in the pathway.Serine is essential for synthesis of proteins and other biomolecules needed for cell proliferation,including nucleotides,phosphatidyl-serine,and sphingosine.Recent studies found that subsets of human malignant cancers have high levels of PHGDH,a key enzyme for serine biosynthesis,and these cancer cells are dependent on PHGDH for their growth and survival.In this paper we made a review on PHGDH gene about its construction,function and relation with tumors.

Objective To analyze the resistance genes in a muhidrug resistant Klebsiella pneumoniae (MDRKP) strain.Methods A MDRKP strain was isolated from bronchoalveolar lavage fluid in Pediatric Intensive Care Unit of Children's Hospital Affiliated to Soochow University in February 2012.Acquired resistance genes to beta-lactams,aminoglycosides,quinolones,ompK35 and ompK36 gene for outer membrane porin protein,and carbapenems targeting PBP2 gene were analyzed by PCR and verified by DNA sequencing.Results Acquired resistance genes TEM-1,SHV-1 to beta-lactam antimicrobial agents and aac(6′)-I b to aminoglycoside antimicrobial agents were positive in the strain of MDRKP.While 16S rRNA methylase,ompK35 and ompK36 genes for outer membrane porin protein were negative.Compared with susceptible strains,there were 9 synonymous mutations in PBP2 gene sequence of this MDRKP strain,but the amino acid sequences were the same.No mutation in quinolone resistance determining region (QRDR) was observed.Conclusion The multidrug resistance of the isolated Klebsiella pneumoniae strain may be related to 2 kinds of beta-lactam acquired resistance genes,1 kind of aminoglycoside acquired resistance gene,ompK35 and ompK36 genes defects and synonymous mutation in PBP2 gene.

Insulin-like growth factor binding protein 7 exert modulatory function in insulin-like growth factor/insulin(IGF/INS) protein network by carrying and transiting IGF/INS,or prolonging their half-life.IGFBP7 has strong ability to bind insulin and low affinity to IGFs and plays a role in either IGFs-dependent way or IGFs-independent way.IGFBP7 involves in multiple function such as cell proliferation,adhesion,invasion,migration and tumor vascular formation through several signaling pathways.