H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

OBJECTIVE: To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance. METHODS: The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups. RESULTS: The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI. CONCLUSION The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.
Child ; Humans ; Flow Cytometry ; Leukemia, Myeloid ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics* ; Granulocytes ; Neutrophils ; Immunophenotyping

OBJECTIVE: To investigate the effect of miR-22 targeting formin-like protein 2 (FMNL2) on the migration and apoptosis of childhood acute myeloid leukemia (AML) cells. METHOD: Peripheral blood samples from 11 children with AML, 10 children with immune thrombocytopenia, human AML cell lines TF-1a, HL-60, THP-1 and human bone marrow stromal cells HS-5 were used as the research objects. UniCel DxH 800 automatic hematology analyzer detected platelet count, hemoglobin, and white blood cell count in peripheral blood samples, and RT-qPCR detected miR-22 expression in peripheral blood samples and AML cells. HL-60 cells were transfected with Lipofectamine^TM 2000 kit, the experiments were divided into seven groups: blank (no cells transfected), miR-NC, miR-22 mimics, si-NC, si-FMNL2 , miR-22 mimics+OE-NC and miR-22 mimics+OE-FMNL2 . RT-qPCR was used to detect the expression of miR-22 in each group. Transwell was used to detect cell migration. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter gene detection experiments verified the targeting relationship between miR-22 and FMNL2 . Western blot was used to detect the expression of FMNL2 protein. RESULTS: Compared with the control group, the number of leukocytes in the peripheral blood of children with AML was significantly increased (P <0.001), while the concentration of hemoglobin and the number of platelets were significantly decreased P <0.001). The expression level of miR-22 in peripheral blood of children with AML was significantly lower than that in control group (P <0.001). Compared with HS-5 cells, the expression levels of miR-22 in TF-1a, HL-60, and THP-1 cells were significantly decreased (P <0.05), and in HL-60 cells was the lowest. Therefore, HL-60 cells were selected for subsequent experiments. Up-regulation of miR-22 or silencing of FMNL2 could reduce the number of migrating cells and increase apoptosis rate (P <0.05). MiR-22 targeted and negatively regulated the expression of FMNL2 . FMNL2 overexpression reversed the effects of up-regulated miR-22 on migration and apoptosis of HL-60 cells. CONCLUSION MiR-22 can inhibit the migration and promote apoptosis of HL-60 cells by down regulating the expression of FMNL2 .
Humans ; Child ; MicroRNAs/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Cell Proliferation ; Apoptosis ; Myeloproliferative Disorders ; Cell Movement ; Hemoglobins ; Cell Line, Tumor ; Formins

OBJECTIVE: To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML). METHODS: The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed. RESULTS: Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified). CONCLUSION D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.
Aged ; Male ; Female ; Humans ; Aged, 80 and over ; Decitabine/therapeutic use* ; Retrospective Studies ; Cytarabine/therapeutic use* ; Prognosis ; Mutation ; Leukemia, Myeloid, Acute/genetics*

Peroxisome proliferator-activated receptors γ (PPARγ) is a master regulator that controls energy metabolism and cell fate. PPARγ2, a PPARγ isoform, is highly expressed in the normal prostate but expressed at lower levels in prostate cancer tissues. In the present study, PC3 and LNCaP cells were used to examine the benefits of restoring PPARγ2 activity. PPARγ2 was overexpressed in PC3 and LNCaP cells, and cell proliferation and migration were detected. Hematoxylin and eosin (H&E) staining was used to detect pathological changes. The genes regulated by PPARγ2 overexpression were detected by microarray analysis. The restoration of PPARγ2 in PC3 and LNCaP cells inhibited cell proliferation and migration. PC3-PPARγ2 tissue recombinants showed necrosis in cancerous regions and leukocyte infiltration in the surrounding stroma by H&E staining. We found higher mixed lineage kinase domain-like (MLKL) and lower microtubule-associated protein 1 light chain 3 (LC3) expression in cancer tissues compared to controls by immunohistochemistry (IHC) staining. Microarray analysis showed that PPARγ2 gain of function in PC3 cells resulted in the reprogramming of lipid- and energy metabolism-associated signaling pathways. These data indicate that PPARγ2 exerts a crucial tumor-suppressive effect by triggering necrosis and an inflammatory reaction in human prostate cancer.
Animals ; Cell Proliferation ; Humans ; Male ; Mice ; PC-3 Cells ; PPAR gamma/genetics* ; Prostatic Neoplasms/genetics* ; Signal Transduction ; Xenograft Model Antitumor Assays

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G^-) bacteria (62.8%), 40 Gram-positive (G⁺) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G⁺ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;
Bacteremia/epidemiology* ; Bacteria ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; Sepsis

OBJECTIVE: To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis. METHODS: Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database. RESULTS: There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database. CONCLUSION These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.
Computational Biology ; Gene Expression ; Gene Expression Profiling ; Humans ; Microarray Analysis ; Myelodysplastic Syndromes/genetics* ; Protein Interaction Maps

OBJECTIVE: To distinguish clinical features, safety and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) in patients after bilioenteric anstomosis based on retrospectively analyzed clinical data and endoscopy procedures. METHODS: Data extracted from patients after bilioenteric anstomosis due to biliary disease treated with ERCP from January 2005 to December 2021 in the Department of Gastroenterology, Peking University Third Hospital were retrospectively analyzed. Clinical data and endoscopic pictures were reevaluated and analyzed. The patients were divided into three groups, including the patients with choledochoduodenostomy (CDD), Roux-en-Y hepaticojejunostomy (RYHJ) and Whipple. Differences between ERCP success and failure were conducted. RESULTS: In the study, 89 cases with 132 ERCP procedures were involved, 9-80 years old, median 57 years old, containing 4 CDD, 30 RYHJ, 54 Whipple and 1 bile duct ileocecal anastomosis patients; The time between ERCP and surgery were 30 (1-40), 2.75 (0.5-14), 2 (0.3-19), and 10 years, respectively; The time between surgery and symptom were 240 (3-360), 12 (1-156), 22 (0-216), and 60 months, respectively. Fifty percent of CDD could succeed only under local anaesthesia, RYHJ (96.7%) and Whipple (100.0%) needed under general anaesthesia (P < 0.001). Successful first entry rates of CDD, RYHJ and Whipple were 100.0%, 40.0% and 77.8%, respectively. After changing the endoscopy type, successful entry rate could increase to 43.3% of RYHJ and 83.3% of Whipple. The successful entry rate of different anastomotic methods was significant (P < 0.001). The cannulation success rates of CDD, RYHJ and Whipple were 100.0%, 53.8% and 86.7% respectively, with significant difference between the groups (P=0.031). ERCP success rates of CDD, RYHJ and Whipple were 100.0%, 33.3% and 78.8% respectively, with significant difference between the groups (P < 0.001). Complications were found in 23.9% (21/88) patients, including infection (14.8%), pancreatitis (9.2%), bleeding (3.4%), and perforation (2.3%) ranked by incidence. Causes of ERCP in post bilioenteric anstomosis were anastomotic stenosis (50.0%, benign 39.3%, malignant 10.7%), choledocholithiasis (37.5%) and reflux cholangitis (12.5%). Anastomotic method was the only predicting factor of ERCP success in patients after bilioenteric anstomosis (OR=7, 95%CI: 2.591-18.912, P < 0.001). CONCLUSION ERCP in post bilioenteric anstomosis patients with gastrointestinal reconstruction need general anaesthe-sia, with good safety and efficiency. The successful rate of RYHJ was significantly lower than Whipple. Anastomotic method was the only predicting factor of ERCP success.
Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Cholangiopancreatography, Endoscopic Retrograde/methods* ; Anastomosis, Roux-en-Y/methods* ; Retrospective Studies ; Intestine, Small ; Anastomosis, Surgical

OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Caspofungin/therapeutic use* ; Child ; Child, Preschool ; Dyspnea ; Female ; Humans ; Male ; Pneumonia, Pneumocystis/therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Respiratory Sounds ; Retrospective Studies

OBJECTIVE: To improve the collection efficiency of leukapheresis, explore relatively scientific and objective evaluation indicators for collection effect, and observe the effect of high-volume leukapheresis on blood cells and coagulation function. METHODS: A total of 158 times of high-volume leukapheresis were performed on 93 patients with hyperleukocytic leukemia by using continuous flow centrifugal blood component separator. 1/5-1/4 of total blood volume of the patients was taken as the target value of leukocyte suspension for single treatment. In addition, the total number of white blood cells (WBCs) subtracted, value of WBCs reduction, rate of WBCs reduction, decrease value of WBCs count, decrease rate of WBCs count, amount of hemoglobin (Hb) lost, value of Hb lost, decreased value of Hb, total number of platelet (PLT) lost, the value of PLT loss, and decrease value of PLT count were used to comprehensively evaluate the collection effect of leukapheresis and influence on Hb level and PLT count of the patients. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen (Fib) concentration were detected before and after treatment, and the effect of leukapheresis on coagulation function of the patients was observed. RESULTS: The volume of leukocyte suspension collected in a single treatment was 793.01±214.23 ml, the total number of WBCs subtracted was 353.25 (241.99-547.28)×10⁹, the value of WBCs reduction was 86.98 (63.05-143.43)×10⁹/L, the rate of WBCs reduction was 44.24 (28.37-70.48)%, decrease value of WBCs count was 65.73 (37.17-103.97)×10⁹/L, decrease rate of WBCs count was (35.67±23.08)%, the amount of Hb lost was 17.36 (12.12-24.94) g, the value of Hb lost was 4.31 (3.01-6.12) g/L, decreased value of Hb was 4.80 (-1.25-9.33) g/L, total number of PLT lost was 222.79 (67.03-578.31)×10⁹, the value of PLT loss was 54.45 (17.29-139.08)×10⁹/L, and decrease value of PLT count was 26.00 (8.38-62.50)×10⁹/L. Before and after a single treatment, the PT was 14.80 (13.20-16.98) s and 15.20 (13.08-16.90) s (z=-1.520, P>0.05), the aPTT was 35.20 (28.68-39.75) s and 35.40 (28.00-39.75) s (z=-2.058, P<0.05), the TT was 17.50 (16.30-18.80) s and 17.70 (16.70-19.10) s (z=-3.928, P<0.001), and the Fib concentration was 2.87±1.13 g/L and 2.64±1.03 g/L (t=7.151, P<0.001), respectively. CONCLUSION High-volume leukapheresis can improve the efficiency of leukapheresis while maintaining the relative stability of the patients' circulating blood volume. The degree of influence on the patients' Hb level, PLT count, Fib concentration, and comprehensive coagulation indicators reflecting the patients' intrinsic and cxtrinsic coagulation activity is within the body's compensation range.
Blood Coagulation Tests ; Fibrinogen ; Hemoglobins ; Humans ; Leukapheresis ; Leukemia