Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Clinical characteristics of patients with odontogenic sinusitis underwent endoscopic sinus surgery / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the clinical features of patients with odontogenic sinusitis (OS) treated by endoscopic sinus surgery (ESS). Methods: A retrospective investigation was carried out in our 27 (16 males and 11 females) cases with OS aged (49.74±14.42) years old. Subjects were hospitalized between January 2018 and November 2020 from Department of Otorhinolaryngology Head and Neck Surgery, Beijing Chaoyang Hospital. The medical history, symptoms, result of nasal endoscopy and paranasal sinus computed tomography (CT) were analyzed statistically by SPSS 19.0. Results: OS mainly occured on unilateral sinuses, with a duration of (8.56±11.79) months. Seventy point four percent (19/27) of the patients had a course within six-month, only 11% was over 12 months (3/27). Symptoms mostly showed as nasal obstruction (88.9%; 24/27), runny nose (81.5%; 22/27), nasal stinks (16/19) and postnasal drip (10/10). Sixty-three percent (17/27) of the OS patients had a dental history. Nasal endoscopic examination revealed a swelling of the ostiomeatal complex (77.8%; 21/27), medial wall interhal displacement of maxillary sinus (55.6%; 15/27), white emulsion-like purulent secretion in the middle meatus (70.4%; 19/27) and nasal polyps (59.3%; 16/27). Etiology of OS included implant-related problems (14.8%; 4/27) and periodontal disease (85.2%; 23/27). Conclusions: OS is usually unilateral sinusitis with a short history. Its clinical features show nasal stinks, white emulsion-like purulent secretion in the middle meatus and imaging findings of unilateral maxillary sinusitis with tooth-related lesions.

Nucleocytoplasmic transport and neurodegenerative diseases / 药学学报

Nucleocytoplasmic transport is the basic cellular activity of eukaryotic cells, which plays a role in cell physiological and pathological processes. A large amount of evidences indicate that impaired nucleocytoplasmic trafficking has emerged as a mechanism contributing to the pathology of neurodegenerative diseases. The regulation of nucleocytoplasmic transport is crucial to elucidate the pathogenesis and intervention in the neurodegenerative diseases. This article summarizes the evidences in disturbed nucleocytoplasmic transport of neurodegenerative diseases in the past two decades, further explores the directions and provides a theoretical basis for the pathogenesis and drug targets in neurodegenerative diseases.

Clinical Characteristics and Prognosis Analysis of Pediatric Severe Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and factors affecting prognosis in children with severe aplastic anemia (SAA).@*METHODS@#Two hundred and five children with SAA treated in our department from January 2008 to April 2018 were selected, and the clinical characteristics and factors affecting prognosis were retrospectively analyzed.@*RESULTS@#Among 205 SAA children, the effective rate (CR+PR) at 3, 6 and 12 months after immunosuppressive therapy (IST) treatment was 50.9%, 59.0% and 73.9%, respectively, and 5-year overall survival rate was 93.1%±2.0%. Univariate analysis showed that 5-year overall survival rate of SAA children of spontaneous delivery was higher than that of cesarean section (P=0.039), while multivariate analysis showed that birth way had no significant influence on 5-year overall survival rate (P>0.05). The response rate at 3 months after IST of children with a recent history of decoration before SAA onset was higher than those without history of decoration (P<0.05).@*CONCLUSION@#Most of the SAA children can achieve high response rate and overall survival rate. Patients with recent history of home/school decoration may be the factor affecting hematological response after 3 months of IST, but have no influence on long-term overall survival.

The Correlation of Minimal Residual Disease with Prognosis in TCF3-PBX1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1@*METHODS@#55 cases of paediatric TCF3-PBX1@*RESULTS@#Among the 55 children with TCF3-PBX1@*CONCLUSION@#The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.

Clinical characteristics of clonal evolution after immunosuppressive therapy in children with severe/very severe aplastic anemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).</p><p><b>METHODS</b>The clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.</p><p><b>RESULTS</b>The 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×10/L, CD3T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.</p><p><b>CONCLUSIONS</b>The children with SAA/VSAA who have an increased CD3T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.</p>

Simultaneous determination of thirteen constituents in Jiuwei Qianghuo Oral Liquid by RP-HPLC / 中草药

Objective: To establish an HPLC method for the simultaneous determination of catalpol, liquiritin, ammonium glycyrrhizinate, asarinin, verbascoside, atractylodin, ferulic acid, imperatorin, notopterol, isoimperatorin, baicalin, prim-O-glucosylcimifugin, and 5-O-methylvisammioside in Jiuwei Qianghuo Oral Liquid (JQOL). Methods: The analysis was performed on Zorbax Eclipse XDB-C18 column (250 mm×4.6 mm, 5 μm) by gradient elution of acetonitrile-0.005 mol/L KH2PO4 (adjusting to pH 3.0 with phosphoric acid) (15:85). The flow rate was 1.0 mL/min. Results: The linear ranges of catalpol, liquiritin, ammonium glycyrrhizinate, asarinin, verbascoside, atractylodin, ferulic acid, imperatorin, notopterol, isoimperatorin, baicalin, prim-O-glucosylcimifugin, and 5-O-methylvisammioside were 2.08-31.22 μg/mL (r=0.9995), 4.01-60.15 μg/mL (r=0.9992), 10.09-151.31 μg/mL (r=0.9992), 4.98-74.63 μg/mL (r=0.9994), 2.05-30.74 μg/mL (r=0.9996), 4.10-61.46 μg/mL (r=0.9996), 2.93-43.98 μg/mL (r=0.9993), 2.04-30.66 μg/mL (r=0.9995), 12.54-181.55 μg/mL (r=0.9997), 53.95-89.23 μg/mL (r=0.9995), 12.05-180.68 μg/mL (r=0.9995), 5.97-89.51 μg/mL (r=0.9994), and 7.99-119.82 μg/mL (r=0.9996). The average recoveries (n=6) were 98.8% (RSD=1.9%), 98.6% (RSD=1.8%), 101.2% (RSD=1.5%), 99.4% (RSD=0.8%), 100.1% (RSD=0.6%), 99.7% (RSD=0.9%), 98.9% (RSD=1.2%), 99.4% (RSD=2.0%), 100.5% (RSD=1.6%), 98.7% (RSD=0.8%), 101.2% (RSD=1.4%), 98.3% (RSD=1.5%), and 99.1% (RSD=1.7%), respectively. The contents of nine batches of the catalpol, liquiritin, ammonium glycyrrhizinate, asarinin, verbascoside, atractylodin, ferulic acid, imperatorin, notopterol, isoimperatorin, baicalin, prim-O-glucosylcimifugin, and 5-O-methylvisammioside were 0.229-0.259 mg/L, 1.231-1.260 mg/L, 0.849-0.877 mg/L, 0.357-0.371 mg/L, 0.149-0.169 mg/L, 0.941-0.967 mg/L, 0.529-0.547 mg/L, 0.269-0.294 mg/L, 1.039-1.067 mg/L, 0.043-0.064 mg/L, 3.631-3.649 mg/L, 0.157-0.183 mg/L, and 0.068-0.084 mg/L. Conclusion: This method is simple and rapid, and can be used for the quality control of JQOL with satisfactory separation and repeatability.

Clinical features of childhood refractory cytopenia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features of patients with refractory cytopenia of childhood (RCC).</p><p><b>METHODS</b>The clinical data of 1 420 children (0-14 years old) with an initial diagnosis of non-severe aplastic anemia between January 1990 and June 2013 were retrospectively analyzed. Bone marrow cell morphology and histopathology were re-evaluated, and the patients were re-classified using the criteria proposed in the 2008 edition of the World Health Organization classification of RCC in hematopoietic and lymphoid tumor tissues. The clinical outcomes were followed up every 3-6 months.</p><p><b>RESULTS</b>Among all the 1 420 cases, 152 (10.7%) were reassessed as RCC. Patients with RCC had a lower level of hemoglobin and a higher percentage of fetal hemoglobin than those with non-severe aplastic anemia. Of the patients with RCC, 21.5% showed abnormal karyotypes at diagnosis. The median follow-up period for all patients was 36 months (ranging from 1 to 283 months). The rates of complete response, partial response, and no response to cyclosporine and androgen treatment in RCC patients were 19.0%, 26.7%, and 54.3%, respectively. The 5- and 10-year prospective overall survival rates of RCC patients were 87.9% and 72.4%, respectively. The 5- and 10-year prospective clonal evolution rates were 15.3% and 20.0%, respectively. The 2-year prospective incidence of newly diagnosed karyotype abnormality after the initial diagnosis was 3.6%. The 5- and 10-year prospective leukemia transformation rates were 10.0% and 20.0%, respectively.</p><p><b>CONCLUSIONS</b>RCC shows clinical features similar to adult myelodysplastic syndrome. Children with RCC have a poor prognosis, an increased risk of transformation to leukemia, and a low response rate to cyclosporine treatment.</p>

Prognostic Value of Prednisone Response in CCLG-ALL 2008 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To ovaluate the prognostic value of prednisone response in treatment regimes of children with acute lymphoblastic leukemia.</p><p><b>METHODS</b>A total of 598 newly diagnosed ALL patients were enrolled and received prednisone pre-treatment. Based on the peripheral lymphoblast count on day 8, these patients were divided into 2 groups: prednisone good response (PGR) and prednisone poor response (PPR). PPR patients were classified into high risk group immediately and then received intensed chemotherapy. The all enrolled patients were followed up and the clinical features and treatment outcomes of the two groups were analyzed.</p><p><b>RESULTS</b>Compared with PGR group, PPR group had different characteristics. They were older in age and had higher initial white blood cell count (P<0.05). T-cell ALL (T-ALL) and Philadelphia chromosome positive ALL (Ph+ ALL) were frequent in PPR group (P<0.05). Event-free survival (EFS) rate of PPR group was significantly lower than that of PGR group (P<0.05). 2 year event-free survival(EFS) rate of PGR group was (88.3±1.5)%, while the 2-year EFS rate of PPR group was (58.4±5.3)%. 5 year EFS rates of PGR and PPR were (80.8±2.1)% and (53.4±6.0)%, respectively. The EFS rate of PPR group was falling rapidly within 2 years. PPR group had higher relapse rate, and most relapses occurred within 18 months (P<0.05). PPR group had more high incidence of minimal residual disease (MRD) both on day 33 and on week 12 (P<0.05). No significant difference of EFS and relapse time was found between PPR and high risk PGR patients (P>0.05). In multi-variate regression analysis, the PPR, the presence of BCR-ABL1 and MLL were significantly unfavorable factors (P<0.05).</p><p><b>CONCLUSION</b>Prednisone response has been confirmed to be still great prognostic value and PPR children patients have poor outcomes generally. It is likely that the response to prednisone does not make much sense to high risk ALL patients.</p>

Research progress in molecular biology of pediatric myelodysplastic syndrome / 中国当代儿科杂志

Marked differences have been found in molecular characteristics between pediatric and adult myelodysplastic syndrome (MDS) patients. The incidence of gene mutations associated with myeloid malignances in pediatric patients is lower than in adults, while the incidence of aberrant methylation is similar between them. It is also worth noting that novel molecular factors such as mitochondrial DNA mutations may play a role in the pathogenesis of childhood MDS. This article summarizes research advances in molecular biology of pediatric MDS.

Clinical application of Sniffin' Sticks olfactory psychophysical measurements / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVES</b>To establish the normal value of Sniffin' Sticks test in Chinese population and to explore it's clinical application in China.</p><p><b>METHODS</b>One hundred and five healthy volunteers were choosen from the department of physical examination of Beijing Tongren Hospital between 2007 and 2013. Another 165 patients complained of abnormal olfactory function were obtained from the outpatient clinic of the department of otorhinolaryngology head and neck surgery in the same period and were divided into two groups: 92 in hyposmia and 73 in functional anosmia group. The 270 subjects were divided into 3 subgroups:younger group ( <35 years of age), middle-age group (35-55 years of age) and older group ( > 55 years of age). The olfactory functions were examined with Sniffin' Sticks test and T & T test, respectively. All analyses were performed using SPSS 12.0 software.</p><p><b>RESULTS</b>For the normal value of Sniffin' Sticks test, TDI score was > 30.12 for younger group, > 27.37 for middle-age group and > 20.43 for older group; the mean TDI score was 32.12 ± 3.95 for healthy group, 17.52 ± 10.37 for hyposmia and 3.56 ± 3.49 for functional anosmia group; the differences in TDI score, olfactory threshold, discrimination threshold and identification threshold between healthy group and olfactory dysfunction group with different ages had statistical significance (Younger group: FTDI = 125.136, P = 0.000; FT = 49.454, P = 0.000;FD = 89.037, P = 0.000; FI = 39.888, P = 0.000; Middle-age group: FTDI = 190.240, P = 0.000; FT = 128.374, P = 0.000;FD = 174.122, P = 0.000;FI = 178.945, P = 0.000;Older group: FTDI = 72.992, P = 0.000; FT = 26.599, P = 0.000; FD = 77.119, P = 0.000; FI = 88.107, P = 0.000, respectively) . The mean T & T value was -1.00 ± 0.98 for healthy group, 2.27 ± 2.01 for hyposmia and 5.89 ± 0.14 for functional anosmia group. T & T score between healthy group and olfactory dysfunction group with different ages had statistical significance (Fyounger = 158.144, P = 0.000; Fmiddle-age = 247.695, P = 0.000; Folder = 70.579, P = 0.000, respectively). TDI score of the Sniffin' Sticks test result was correlated with T & T value (r = -0.927, P < 0.01); T & T threshold was correlated with the olfactory threshold, discrimination threshold and identification threshold of Sniffin' Sticks test (rT = -0.846, P < 0.01, rD = -0.908 P < 0.01, rI = -0.864, P < 0.01, respectively).</p><p><b>CONCLUSIONS</b>Sniffin' Sticks test and T & T olfactometry are able to differentiate normosmia from hyposmia and anosmia with high reliability and consistency in test results.Sniffin' Sticks test can assess subject's olfactory function status more thoroughly and is suitable for application in Chinese population.</p>

The levels of liver enzymes and atypical lymphocytes are higher in youth patients with infectious mononucleosis than in preschool children

BACKGROUND/AIMS: Infectious mononucleosis (IM) is the clinical presentation of primary infection with Epstein-Barr virus. Although the literature contains a massive amount of information on IM, most of this is related specifically to only children or adults separately. In order to distinguish any differences between preschool children and youth patients, we retrospectively analyzed their demographic and clinical features. METHODS: Records of patients hospitalized from December 2001 to September 2011 with a diagnosis of IM were retrieved from Peking University First Hospital, which is a tertiary teaching hospital in Beijing. The demographic data and clinical characteristics were collected. RESULTS: IM was diagnosed in 287 patients during this 10-year period, with incidence peaks among preschool children (15 and <24 years old, 101/287, 35.2%). Although the complaints at admission did not differ between these two patient groups, the incidence of clinical signs (tonsillopharyngitis, lymphadenopathy, hepatomegaly, and edema of the eyelids) was much higher in preschool children. The incidence of liver lesion and percentage of atypical lymphocytes were significantly higher in the youth group (P<0.001), and the average hospital stay was longer in this group. Pneumonia was the most common complication, and there was no case of mortality. CONCLUSIONS: The incidence of IM peaks among preschool children and youth patients in Beijing, China. The levels of liver enzymes and atypical lymphocytes increase with age.

Effect of erlotinib on proliferation and differentiation of JAK2V617F-positive cells in vitro / 中国实验血液学杂志

The aim of this study was to investigate the effect of erlotinib on proliferation and differentiation of JAK2V617F-positive cells in vitro, and to provide experimental evidence of erlotinib for potential target therapy in polycythemia vera. Colony forming assays were used to detect the effect of erlotinib on differentiation of hematopoietic progenitor cells from bone marrow of polycythemia vera patients, and MTT method was used to measure the proliferation of HEL cell line containing the JAK2V617F mutation. The results showed that erlotinib 5 µmol/L inhibited the differentiation of JAK2V617F-positive hematopoietic progenitor cells into hematopoietic colonies in vitro, while it had almost no effect on normal hematopoietic progenitor cells from the patients. Erlotinib had inhibitory effect on the proliferation of HEL cell line in a dose dependent manner. The IC(50) was 4.1 µmol/L. It is concluded that erlotinib can inhibit proliferation and differentiation of JAK2V617F-positive cells to a certain extent in vitro.

Development and evaluation of a quality of life scale specific to patients with congenital external and middle ear malformation / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To develop a quality of life scale for patients with congenital external and middle ear malformation, and to explore its reliability and validity.</p><p><b>METHODS</b>The initial quality of life scale for patients with congenital external and middle ear malformation was constructed based on quality of life scales from home and abroad. A total of 140 patients with congenital external and middle ear malformation had been recruited in the study. After pretest and item sifting, the quality of life scale was constructed, and its reliability and validity were evaluated.</p><p><b>RESULTS</b>Eighteen-item quality of life scale for patients with congenital external and middle ear malformation was constructed, which included three parts: physiological function, psychological status and social interaction. The retest reliability was 0.878; split-half reliability coefficient and Cronbach's alpha coefficient were 0.927 and 0.899, respectively. The results of factor analysis showed satisfactory construct validity. The reliability and validity of this scale was consistent with the demands of psychometrics.</p><p><b>CONCLUSION</b>Congenital external and middle ear malformation quality of life scale is believable and effective, which can be used for clinical practice.</p>