A Patient with Sequential Diseases of Langerhans Cell Sarcoma, Langerhans Cell Histiocytosis, and Acute Lymphoblastic Leukemia / 罕见病研究

Langerhans cell histiocytosis(LCH)and Langerhans cell sarcoma(LCS)are characterized by clone proliferation of Langerhans-type cells, which may occur concurrently or sequentially with T-cell acute lymphoblastic leukemia (T-ALL) and other Lymphoid neoplasms. A 15-year old female patient diagnosed with T-ALL developed LCH involving multiple systems during maintenance chemotherapy of T-AL. After treated with chemotherapy with improved result, the patient showed progression of the illness and refractory to the second-line treatment. We found c.G35A (p.G12D)mutation in the KRAS gene and used the targeted drug Trametinib for treatment. The treatment proved effective, leading to partial remission within a week. Three months after Trametinib treatment, the patient developed new lymphadenopathy. Biopsy revealed the existence of LCS. The disease progressed quickly, and the patient died 7 days after diagnosis of LCS. The case of patients with T-ALL then developing LCH and LCS sequentially is extraordinarily rare. The causes of the case is unclear and may be related to cell transdifferentiation, clonal evolution, and chemotherapy. Targeted drugs can contain this disease for a short time.

Clinical research on childhood Langerhans cell histiocytosis with skin-limited lesion / 中华实用儿科临床杂志

Objective:To understand the clinical characteristics and prognosis of Langerhans cell histiocytosis (LCH) with skin-limited lesion.Methods:A retrospective analysis was performed on clinical characteristics and prognosis of 16 skin-limited LCH patients, out of 578 LCH patients who were hospitalized in Beijing Children′s Hospital during December 2013 to June 2018.Results:A total of 16 skin-limited LCH cases, accounted for 2.7% of all 578 cases, were included.Among which, sex ratio (male vs.female) was 1.28∶1.00.Median ages of skin eruption occurrence and of diagnosis of the disease were 3.5 months (3 days to 2 years and 5 months) and 6 months (2 months 14 days to 2 years and 8 months) in this group.Among the 16 cases, seborrheic dermatitis-like lesions(11 cases, 68.7%) was the most common, and the trunk was most frequently involved[75.0% (12 cases)]. Serine/threonine protein kinase gene V600E [ BRAF (p.V600E)] mutation was detected in pathological specimens from 10 skin-limi-ted cases, with 9 cases being positive.Plasma samples from 5 positive cases were further detected for BRAF (p.V600E) mutation, and 4 positive results were gained.Of all 16 patients, 11 cases (68.7%) were treated.Remission were achieved in 3-6 months from treatment start in patients treated whether according to the Histiocyte Society′s LCH-2009 protocol for 25 weeks(6 cases, 37.5%), or with topical mometasonefuroate for 3 months (3 cases, 18.8%). Two patients(12.5%) with solitary cutaneous lesions underwent excision biopsy (one face and one prepuce) and were considered to be in remission immediately after surgery.None of these patients suffered from the recurrence of the disease.The remaining 5 patients (31.3%) with skin-limited LCH were just evaluated regularly, and achieved remission in 3-6 months of commencing observation.Among these untreated patients, 1 with consistently positive BRAF (p.V600E) mutation in plasma had bone involvement in the 24 th month of assessment, and was then treated based on the Histiocyte Society′s LCH-2009 Protocol.No clinical or imageological evidence supporting disease progression was found on this patient.Median follow-up period was 32.8 months (2.9-63.9 months). Except one patient, none of the rest cases had active disease till follow-up ended.Two-year event free survival(EFS) of this research was (92.3± 7.4)%.There was no significant difference between EFS of treated group and that of observation group( χ2=1.250, P=0.264). Conclusions:Skin-limited LCH often occurs in infants and newborns, with strong heterogeneity in clinical manifestations, laboratory indicators, and pathogenesis.Seborrheic dermatitis-like lesions were the most common cutaneous type.The prognosis of the patients is excellent despite progressing into multisystem involvement can be seen in a few patients.

Prognostic significance of plasma and whole blood Epstein-Barr virus-DNA load during treatment in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis / 中华实用儿科临床杂志

Objective:To evaluate the prognostic value of Epstein-Barr virus (EBV)-DNA level in plasma and whole blood in treatment of children with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:Clinical data of 66 children with EBV-HLH, who were admitted to the Hematology and Oncology Center of Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2017 were retrospectively reviewed and analyzed.The data included the dynamic changes of the EBV-DNA level in plasma (P-EBV-DNA) and whole blood (W-EBV-DNA) at the time of admission, 2 and 4 weeks after treatment.P-EBV-DNA was divided into the positive group and the negative group according to the copy number of EBV-DNA, and W-EBV-DNA was divided into the high and the low level group by the receiver operating characteristic curve(ROC); the incidence of poor prognosis was compared between different groups by Chi- Square test; the event-free survival (EFS)was evaluated by the Log- Rank test to identify its prognostic significance. Results:The analysis showed that both P-EBV-DNA and W-EBV-DNA at admission could not be associated with a poor outcome; P-EBV-DNA (≥500 copies/mL) or W-EBV-DNA [>(5.04-5.09)×10 5 copies/mL]after 2 and 4 weeks of treatment could be a good marker of a poor outcome and progression-free survival ( P<0.001). Besides, central nervous system (CNS) involvement ( P=0.025), sever leukopenia(WBC≤3×10 9/L, P=0.031), neutropenia (ANC ≤0.5×10 9/L, P=0.041), albumin reduction (≤26 g/L, P=0.012) and hemoglobin decrease (≤90 g/L, P=0.023) at diagnosis are also associa-ted with worse outcomes.In multivariate analysis, only P-EBV-DNA at 4 th week and CNS involvement were indepen-dent prognostic factors ( HR=7.139, P=0.032 and HR=6.455, P=0.042, respectively). The prognostic value of W-EBV-DNA at different time points and P-EBV-DNA after 2 weeks of treatment had a lower prognostic value. Conclusions:The P-EBV-DNA level after 4 weeks of treatment is a promising risk indicator for early diagnosis of disease and early recognition of poor prognosis in EBV-HLH children, so it provides the guidance for optimal treatment.

Analysis of five cases of hepatitis associated aplastic anemia presenting with hemophagocytic lymphohistiocytosis at onset / 中华儿科杂志

Objective@#To discuss the clinical characteristics and management approaches to hepatitis associated aplastic anemia (HAAA) presenting as hemophagocytic lymphohistiocytosis (HLH) at onset.@*Methods@#The clinical data and laboratory results of hospitalized 5 HAAA patients presenting as HLH at onset in Beijing Children′s Hospital from January 2017 to May 2019 were analyzed retrospectively.@*Results@#Among 5 cases, there were 4 males and 1 female. The age of onset was 6.0 (2.7-12.7) years. All patients presented with high fever, hepatomegaly, hepatic dysfunction (aspartate aminotransferase 1 716 (1 409-2 570) U/L, alanine aminotransferase 1 699 (937-2 540) U/L) at onset. After admission, the laboratory results showed pancytopenia (white blood cell 1.2 (0.6-6.7) ×109/L, haemoglobin 94 (65-111) g/L, blood platelet 29 (10-41) ×109/L), decreased fibrinogen (1.3 (1.1-2.5) g/L), significantly elevated triglyceride (4.0 (2.8-5.1) mmol/L), ferritin (1 766 (399-5 253) μg/L) and soluble CD25 (27 457 (9 625-44 000) ng/L). Hemophagocytosis was found in the bone marrow smears of all 5 patients. The diagnosis of acute hepatitis and HLH was confirmed. During the treatment of HLH, the blood cells remain below normal level and the further biopsy of bone marrow (iliac bone) indicated low myeloproliferation. After exclusion of congenital bone marrow failure syndromes and other pancytopenic diseases, HAAA was confirmed. After the diagnosis of HAAA, 1 patient received antithymocyte globulin (ATG) and cyclosporin treatment in our hospital, 1 patient received allogeneic stem cell transplantation (HSCT) in other hospital, 2 patients received ATG in other hospitals. Only 1 patient died of severe infection.@*Conclusions@#HAAA can present as HLH at onset. It is mainly manifested by high fever, acute severe hepatitis, pancytopenia, elevated ferritin and hemophagocytosis in the bone marrow. The diagnosis of HAAA should be considered whenever cytopenia could not completely corrected while apparent improvement of HLH and hepatitis related complications were improved after immunosuppressive therapy. ATG or HSCT treatment should be performed as soon as the diagnosis of severe or transfusion dependent aplastic anemia is confirmed.

Study on the relationships between the levels of trace elements and nutritional status of preschool children in Guangzhou / 公共卫生与预防医学

Objective To investigate the levels of trace elements in preschool children in Guangzhou and their relationships with nutritional status, and to provide a scientific basis for guiding children's nutritional diet and timely and reasonable supplementation of trace elements. Methods A cross-sectional study was used to perform physical examinations and collect blood samples from 5 002 children who were examined in the Department of Pediatric Health of a Maternal and Child Health Hospital in Guangzhou in 2018. The levels of trace elements including iron, zinc and copper were detected by atomic absorption spectrometer. Results The median (upper and lower quartile) levels of iron, zinc and copper for preschool children in a district of Guangzhou were 7.80 (7.39, 8.19) mmol / L, 69.0 (61.0, 76.5) μmol / L, 18.6 (15.9, 21.4) μmol / L. There was no significant difference in the levels of iron, zinc and copper between different genders (P>0.05). The levels of iron and zinc increased significantly with the age of children (P=0.000). There was no significant difference in the level of copper in different ages (P>0.05). The prevalence rates of iron, zinc and copper deficiency in preschool children were 14.93%, 21.93% and 0.24%, respectively, and there was no significant difference between different genders (P>0.05).There were no significant differences in the prevalence of iron and copper deficiency in different ages (P>0.05), while the zinc deficiency rate decreased with the age of children (P = 0.000). (P0.05). The prevalence rates of iron and zinc deficiency in children with malnutrition, overweight and obesity were higher than those in normal children. There was no significant difference in the prevalence of copper deficiency in children with different nutritional status (P>0.05). Conclusion The prevalence of iron, zinc deficiency is high in preschool children in Guangzhou. Preschool children with malnutrition, overweight and obesity are more prone to iron and zinc deficiency.

Clinical analysis of pediatric Langerhans cell histiocytosis with craniofacial bone involvement / 中华实用儿科临床杂志

Objective To investigate the clinical characteristics and outcomes of pediatric Langerhans cell histiocytosis (LCH) with craniofacial bone involvement.Methods A retrospective analysis was performed on 145 pediatric LCH patients with craniofacial bone involvement registered at Beijing Children's Hospital Affiliated to Capital Medical University from January 2007 to July 2013.The patients were divided into 2 groups:central nervous system risk craniofacial bone involvement group(CNS-RISK) and non-central nervous system risk craniofacial bone involvement group(non-CNS-RISK).All patients were assessed at 5 weeks,11 weeks,25 weeks and 52 weeks respectively after chemotherapy started,and 3 months,6 months,1 year and 3 years after chemotherapy withdrawal.Statistics and related risk analysis was performed respectively.Results A total of 145 craniofacial bone involved LCH cases were included,which was composed of 62.5％ of 232 LCH cases hospitalized during the same period.The median age of these patients was 29 months,and median follow-up time period was 31 months.The most commonly involved craniofacial bone was parietal bone(78 cases,53.8％),followed by temporal bone(59 cases,40.7％) and frontal bone(57 cases,39.3％).The onset age was significantly different (26 months vs.54 months,Z =-2.777,P ＜ 0.05) between CNS-RISK group (103 cases) and non-CNS-RISK group (42 cases).Moreover,compared with non-CNS-RISK group,CNS-RISK group showed higher ratio of patients classified as multisystem involvement of risk organs (72/103 cases,69.9％) vs.(15/42 cases,35.7％) (x2 =16.908,P ＜ 0.05),and a higher rate of overall relapse rate (45/103 cases,43.7％) vs.(7/42 cases,16.7％) (x2 =9.427,P ＜ 0.05),a lower survival rate of 3-year relapse-free survival rate [(66.9 ± 5.7) ％ vs.(88.2 ± 7.8) ％,Z =2.205,P ＜ 0.05].The incidence of diabetes insipidus was 13.7％ in 232 LCH patients.Compared with patients without craniofacial bone involvement,patients with craniofacial bone involvement demonstrated a higher rate of diabetes insipidus [(27/145 cases,18.6％) vs.(5/87 cases,5.7％),x2 =7.579,P =0.006].But the incidence of diabetes insipidus showed no statistical difference between CNS-RISK group and non-CNS-RISK group (21.3 ％ and 11.9 ％,x2 =1.760,P =0.185).Diabetes insipidus was not found in single system LCH with Single-Bone CNS-RISK lesions.Till the end of follow-up,1 out of 145 patients died.Among 145 patients,5 cases had a single-bone CNS-RISK lesion.They received systemic chemotherapy.One showed reactivation,and none of them died.Multivariate analysis of variance showed that all the independent factors indicating diabetes insipidus included parietal bone,frontal bone,maxilla and mandible involvement (HR =2.697,3.487,5.425,all P ＜ 0.05),while independent factors indicating relapse included temporal bone,maxilla and mandible involvement (HR =3.712,3.380,all P ＜ 0.05).Conclusions Among involved craniofacial bones,the parietal bone is most commonly involved.LCH occurs averagely at an earlier age in CNS-RISK group,along with lower 3-year relapse-free survival rate,high relapse rate,and more patients classified as multisystem LCH involvement of risk organs.The incidence of diabetes insipidus in children with craniofacial bone involvement with single system CNS-RISK is low.Patients with the parietal bone,frontal bone,maxilla and mandible involvement at diagnosis are at a increasing risk a significantly to develop DI during the course of disease.

Single-center clinical analysis of hereditary thrombocytopenia in children with chronic thrombocytopenia / 中华实用儿科临床杂志

Objective To know the detection rate of hereditary thrombocytopenia (HT) in children with chronic thrombocytopenia and its clinical and laboratory characteristics for an early clinical identification and diagnosis of HT in future.Methods Data of the children with thrombocytopenia,who had been treated in Beijing Children's Hospital from April 2016 to May 2018 and whose present history lasted for more than 1 year and had poor response to immunotherapy were retrospectively collected.HT was screened in these patients by adopting next generation sequencing (NGS).Finally,clinical and laboratory characteristics of these children with HT were summarized and analyzed.Results A total of 161 children with chronic thrombocytopenia were included.Forty-three cases (26.7％) were found to have gene mutations.The genetic rules of the mutant gene,the family verification and the clinical manifestations of the proband and some related laboratory tests were analyzed and 24 cases (14.9％) can be diagnosed as HT.Among the HT patients,the proportion of males and females was 15 ∶ 9,and the median onset of age was 0.58 years,which was significantly lower than that of non-HT cases (the median onset of age was 4.36 years),and the difference was statistically significant (P ＜ 0.001);the proportion of mucosal hemorrhage and visceral hemorrhage (31.8％ and 13.7％) of HT was significantly higher than non-HT cases (15.3％ and 0.6％),and the difference was statistically significant (P ＜ 0.001).Fifty percent of (12/24 cases) cases of HT had positive family history;according to the average platelet volume and platelet morphology in peripheral blood smear,HT could be divided into small platelet HT,positive platelet HT and large platelet HT.Some cases had well response to immunotherapy but seemed easy to relapse during the withdrawal period,while the others responded poorly to therapy.Different clinical manifestations of HT suggest different pathogenesis,which can be divided into the related types of megakaryocyte differentiation defect,megakaryocyte maturation defect,platelet release defect and platelet survival time shortening.Conclusions The pathogenesis and clinical phenotype of HT was different.Some of them were effective for immunotherapy,which were easily confused with immune thrombocy-topenla(ITP).It is clinically necessary to perform NGS in children with thrombocytopenia at early onset,abnormal platelet morphology,prolonged disease course or severe mucosal/visceral hemorrhage,in order to recognize HT timely to avoid delay in diagnosis and poor prognosis.

Efficacy and safety of short course high-dose Dexamethasone as first-line treatment regimen for childhood newly diagnosed immune thrombocytopenia / 中华实用儿科临床杂志

Objective To compare the efficacy and safety of short course and high-dose Dexamethasone (HDD) and conventional Prednisone as first-line strategy for children newly diagnosed as primary immune thrombocytopenia (ITP).Methods This study analyzed pre-experimental data of a single center prospective randomized controlled clinical trial.Newly diagnosed but untreated ITP patients enrolled at the Department of Blood and Cancer Center,Beijing Children's Hospital,Capital Medical University from November 2016 to May 2017 were randomized into HDD group[Dexamethasone 0.6 mg/(kg · d),intravenous injection for 4 days] and Prednisone group [Prednisone 2 mg/(kg · d) for 14-28 days and then tapered within 1-2 months,the course of treatment less than 3 months].Initial response,sustained response and adverse effects after therapy were observed in 2 groups.Results Sixty-six children with ITP were included in the study:32 patients were in the HDD group and 34 patients were in the Prednisone group.Two groups were matched in the baseline characteristics including gender,age,platelet counts and disease course before therapy and bleeding assessment (all P ＞ 0.05).The initial response (the response of HDD group within 10 days of treatment and Prednisone group within 28 days of treatment):overall initial response had no statistical difference between the HDD group and the Prednisone group[90.6％ (29/32 cases) vs.100.0％ (34/34 cases),x2 =1.528,P ＞ 0.05].HDD group had a lower incidence of complete response compared with that in the Prednisone group [54.4％ (19/32 cases) vs.94.1％ (32/34 cases),x2 =11.330,P =0.001];median time of response in two groups showed no statistically difference (2 d vs.1 d,Z =-0.149,P ＞ 0.05).There was no significant difference in the recovery of skin and mucosal bleeding after treatment between the Dexamethasone group and the Prednisone group (Z =-1.413,-1.031,all P ＞ 0.05).The sustained response (the response lasted for up to 6 months and above):overall and complete sustained response had no statistically difference between the HDD group and the Prednisone group [92.9％ (26/ 28 cases) vs.85.3％ (29/34 cases),P =0.594;78.9％ (15/19 cases) vs.81.3％ (26/32 cases),P=1.000].Log-rank test showed no significant difference in the duration of response between 2 groups (P =0.341).The side effects in the Prednisone group included weight gain or Cushing sign (94.1％) and mental and emotional changes (23.5％);in the HDD group 15.6％ of children had infection,without other glucocorticoid-related side effects.There was no significant difference in the incidence of infection between two groups[15.6％ (5/32 cases) vs.26.5 ％ (9/34 cases),P =0.281].All of the above infections were of respiratory tract infections and mild gastrointestinal infections.Conclusions Efficacy of the HDD group in the initial and sustained responses is similar,but side effects were apparently lower compared with that in the Prednisone group.However,a large multicenter randomized controlled clinical study is necessary to confirm this result.

Efficacy and safety of short course high-dose Dexamethasone as first-line treatment regimen for childhood newly diagnosed immune thrombocytopenia / 中华实用儿科临床杂志

Objective@#To compare the efficacy and safety of short course and high-dose Dexamethasone (HDD) and conventional Prednisone as first-line strategy for children newly diagnosed as primary immune thrombocytopenia (ITP).@*Methods@#This study analyzed pre-experimental data of a single center prospective randomized controlled clinical trial.Newly diagnosed but untreated ITP patients enrolled at the Department of Blood and Cancer Center, Beijing Children's Hospital, Capital Medical University from November 2016 to May 2017 were randomized into HDD group[Dexamethasone 0.6 mg/(kg·d), intravenous injection for 4 days]and Prednisone group[Prednisone 2 mg/(kg·d) for 14-28 days and then tapered within 1-2 months, the course of treatment less than 3 months]. Initial response, sustained response and adverse effects after therapy were observed in 2 groups.@*Results@#Sixty-six children with ITP were included in the study: 32 patients were in the HDD group and 34 patients were in the Prednisone group.Two groups were matched in the baseline characteristics including gender, age, platelet counts and disease course before therapy and bleeding assessment (all P>0.05). The initial response (the response of HDD group within 10 days of treatment and Prednisone group within 28 days of treatment): overall initial response had no statistical difference between the HDD group and the Prednisone group[90.6%(29/32 cases) vs.100.0%(34/34 cases), χ2=1.528, P>0.05]. HDD group had a lower incidence of complete response compared with that in the Prednisone group[54.4%(19/32 cases) vs.94.1%(32/34 cases), χ2=11.330, P=0.001]; median time of response in two groups showed no statistically difference (2 d vs.1 d, Z=-0.149, P>0.05). There was no significant difference in the recovery of skin and mucosal bleeding after treatment between the Dexamethasone group and the Prednisone group (Z=-1.413, -1.031, all P>0.05). The sustained response (the response lasted for up to 6 months and above): overall and complete sustained response had no statistically difference between the HDD group and the Prednisone group [92.9%(26/28 cases) vs.85.3%(29/34 cases), P=0.594; 78.9% (15/19 cases) vs.81.3%(26/32 cases), P=1.000]. Log-rank test showed no significant difference in the duration of response between 2 groups (P=0.341). The side effects in the Prednisone group included weight gain or Cushing sign (94.1%) and mental and emotional changes (23.5%); in the HDD group 15.6% of children had infection, without other glucocorticoid-related side effects.There was no significant difference in the incidence of infection between two groups[15.6%(5/32 cases) vs.26.5%(9/34 cases), P=0.281]. All of the above infections were of respiratory tract infections and mild gastrointestinal infections.@*Conclusions@#Efficacy of the HDD group in the initial and sustained responses is similar, but side effects were apparently lower compared with that in the Prednisone group.However, a large multicenter randomized controlled clinical study is necessary to confirm this result.

Clinical analysis of pediatric Langerhans cell histiocytosis with craniofacial bone involvement / 中华实用儿科临床杂志

Objective@#To investigate the clinical characteristics and outcomes of pediatric Langerhans cell histiocytosis (LCH) with craniofacial bone involvement.@*Methods@#A retrospective analysis was performed on 145 pediatric LCH patients with craniofacial bone involvement registered at Beijing Children′s Hospital Affiliated to Capital Medical University from January 2007 to July 2013.The patients were divided into 2 groups: central nervous system risk craniofacial bone involvement group(CNS-RISK) and non-central nervous system risk craniofacial bone involvement group(non-CNS-RISK). All patients were assessed at 5 weeks, 11 weeks, 25 weeks and 52 weeks respectively after chemotherapy started, and 3 months, 6 months, 1 year and 3 years after chemotherapy withdrawal.Statistics and related risk analysis was performed respectively.@*Results@#A total of 145 craniofacial bone involved LCH cases were included, which was composed of 62.5% of 232 LCH cases hospitalized during the same period.The median age of these patients was 29 months, and median follow-up time period was 31 months.The most commonly involved craniofacial bone was parietal bone(78 cases, 53.8%), followed by temporal bone(59 cases, 40.7%) and frontal bone(57 cases, 39.3%). The onset age was significantly different (26 months vs.54 months, Z=-2.777, P<0.05) between CNS-RISK group (103 cases) and non-CNS-RISK group (42 cases). Moreover, compared with non-CNS-RISK group, CNS-RISK group showed higher ratio of patients classified as multisystem involvement of risk organs (72/103 cases, 69.9%)vs.(15/42 cases, 35.7%)(χ2=16.908, P<0.05), and a higher rate of overall relapse rate (45/103 cases, 43.7%) vs. (7/42 cases, 16.7%) (χ2=9.427, P<0.05), a lower survival rate of 3-year relapse-free survival rate [(66.9±5.7)% vs.(88.2±7.8)%, Z=2.205, P<0.05]. The incidence of diabetes insipidus was 13.7% in 232 LCH patients.Compared with patients without craniofacial bone involvement, patients with craniofacial bone involvement demonstrated a higher rate of diabetes insipidus [(27/145 cases, 18.6%) vs.(5/87 cases, 5.7%), χ2=7.579, P=0.006]. But the incidence of diabetes insipidus showed no statistical difference between CNS-RISK group and non-CNS-RISK group (21.3% and 11.9%, χ2=1.760, P=0.185). Diabetes insipidus was not found in single system LCH with Single-Bone CNS-RISK lesions.Till the end of follow-up, 1 out of 145 patients died.Among 145 patients, 5 cases had a single-bone CNS-RISK lesion.They received systemic chemotherapy.One showed reactivation, and none of them died.Multivariate analysis of variance showed that all the independent factors indicating diabetes insipidus included parietal bone, frontal bone, maxilla and mandible involvement(HR=2.697, 3.487, 5.425, all P<0.05), while independent factors indicating relapse included temporal bone, maxilla and mandible involvement(HR=3.712, 3.380, all P<0.05).@*Conclusions@#Among involved craniofacial bones, the parietal bone is most commonly involved.LCH occurs averagely at an earlier age in CNS-RISK group, along with lower 3-year relapse-free survival rate, high relapse rate, and more patients classified as multisystem LCH involvement of risk organs.The incidence of diabetes insipidus in children with craniofacial bone involvement with single system CNS-RISK is low.Patients with the parietal bone, frontal bone, maxilla and mandible involvement at diagnosis are at a increasing risk a significantly to develop DI during the course of disease.

Single-center clinical analysis of hereditary thrombocytopenia in children with chronic thrombocytopenia / 中华实用儿科临床杂志

Objective@#To know the detection rate of hereditary thrombocytopenia (HT) in children with chronic thrombocytopenia and its clinical and laboratory characteristics for an early clinical identification and diagnosis of HT in future.@*Methods@#Data of the children with thrombocytopenia, who had been treated in Beijing Children′s Hospital from April 2016 to May 2018 and whose present history lasted for more than 1 year and had poor response to immunotherapy were retrospectively collected.HT was screened in these patients by adopting next generation sequencing (NGS). Finally, clinical and laboratory characteristics of these children with HT were summarized and analyzed.@*Results@#A total of 161 children with chronic thrombocytopenia were included.Forty-three cases (26.7%) were found to have gene mutations.The genetic rules of the mutant gene, the family verification and the clinical manifestations of the proband and some related laboratory tests were analyzed and 24 cases (14.9%) can be diagnosed as HT.Among the HT patients, the proportion of males and females was 159, and the median onset of age was 0.58 years, which was significantly lower than that of non-HT cases (the median onset of age was 4.36 years), and the difference was statistically significant (P<0.001); the proportion of mucosal hemorrhage and visceral hemorrhage (31.8% and 13.7%) of HT was significantly higher than non-HT cases (15.3% and 0.6%), and the difference was statistically significant (P<0.001). Fifty percent of (12/24 cases) cases of HT had positive family history; according to the ave-rage platelet volume and platelet morphology in peripheral blood smear, HT could be divided into small platelet HT, po-sitive platelet HT and large platelet HT.Some cases had well response to immunotherapy but seemed easy to relapse du-ring the withdrawal period, while the others responded poorly to therapy.Different clinical manifestations of HT suggest different pathogenesis, which can be divided into the related types of megakaryocyte differentiation defect, megakaryocyte maturation defect, platelet release defect and platelet survival time shortening.@*Conclusions@#The pathogenesis and cli-nical phenotype of HT was different.Some of them were effective for immunotherapy, which were easily confused with immune thrombocy-topenla(ITP). It is clinically necessary to perform NGS in children with thrombocytopenia at early onset, abnormal platelet morphology, prolonged disease course or severe mucosal/visceral hemorrhage, in order to recognize HT timely to avoid delay in diagnosis and poor prognosis.

Effect of Ulinastatin on the Expression of TNF-α in the Rabbits with Acute Lung Injury Induced by Underwater Explosion / 现代检验医学杂志

Objective The expression of TNF-α was detected in sera of rabbits treated by ulinastatin with acute lung injury in duced by underwater explosion.Methods Rabbits were randomly divided into two groups such as the injured group and ulinastatin therapy group.Established underwater explosion device was used to cause acute lung injury in rabbits.TNF-α in sera of the rabbits were measured by ELISA at 4,12 and 24 hours after the explosion.The SPSS17.0 software was used to analyze the data and P＜0.05 was considered to be significant.Results There was no significant difference between the concentrations of TNF-α in the sera of rabbits in the injure group (538.20±201.43 ng/L) and that of in the ulinastatin group (386.90± 109.22 ng/L,t=2.088,P=0.051) at 4 hours after burst.However,there was evidently decreased in the level of TNF-α in the ulinastatin group (400.60 ± 78.98 ng/L) compared with the injury group (573.80 ± 178.24 ng/L,t =2.809,P =0.012) at 12 hours after burst.Moreover and TNF-α in the ulinastatin group (356.10 ± 130.99 ng/L) was also decreased compared to the injure group (552.30± 169.64 ng/L,t=2.895,P=0.010) at 24 hours after burst.Conclusion The TNF-α expression in sera of the rabbits in ulinastatin group were dramatically decreased than thai of in injury group at 12 hours after burst,which may be benefit to rabbits with acute lung injury induced by underwater explosion.

Clinical analysis of 217 children with Langerhans cell histiocytosis / 中华实用儿科临床杂志

Objective To investigate the clinical characteristics,treatment,and prognostic factors for Langerhans cell histiocytosis (LCH) in children.Methods A retrospective review of patients diagnosed as LCH was carried out between January 2007 and December 2012 in Beijing Children's Hospital,Capital Medical University.Target patients were divided into multi-organ high-risk groups (Group Ⅰ),multi-organ low-risk groups (Group Ⅱ),single-organ groups (GroupⅢ),and the corresponding intensity of chemotherapy was given.SPSS 17.0 statistical software was used to analyze the findings.The correlations among the affected organ,the early treatment response and the prognosis were analyzed.Results A total of 217 patients were analyzed including 127 boys and 90 girls with ratio of 1.4 ∶ 1.0 and a median age of 36 months (ranged from 2 months to 14 years) on the diagnosis of LCH,and there were 132 cases (60.8％) in group Ⅰ,33 cases (15.3％) in group Ⅱ and 52 cases (23.9％) in group Ⅲ.The median age on diagnosis was 20 months in group Ⅰ,42 months in group Ⅱ and 72 months in group Ⅲ.The most frequently affected organ was the bone (176 cases,81.2％).Among 217 patients,55 cases (25.3％) had recurrence and 12 cases died.The rate of 3-year overall survival was expected to be 90.78％.The rate of 3-year event free survival was expected to be 76.5％.Myelosuppression,liver function damage and infection were the most common side effects due to chemotherapy with the percentages of 48.4％ (105 cases),24.0％ (52 cases) and 12.4％ (27 cases).Risk organs involvement and no-response to initial therapy (after 6 weeks) indicated a worse prognosis (x2 =10.60,12.84,P =0.017,0.001).Conclusions Incidence of LCH in boys is slightly higher than girls in children.Peak age at onset of LCH in children is 1-3 years old.Bone is the most frequent involved organ.Involvement of risk organs and no-response to initial therapy are key factors in determining worse prognosis.A rescue therapy should be introduced earlier in these patients.

Investigation to the Expression of NE and TNF-α in Serum and BALF of Rabbits with Acute Lung Injury Interposed by XueBiJing in Underwater Explosion / 现代检验医学杂志

Objective The concentration of NE and TNF-α was detected for elucidating the change of them in sera and bronchoalveolar lavage fluid (BALF) of rabbits with acute lung injury interposed by XueBiJing therapy in underwater explosion.Methods Underwater explosion decive was applied to cause acute lung injury of rabbits.The 20 rabbits were randomly divided into two groups which were injury group and XueBiJing therapy group,respectively.The concentration of NE and TNF-α in sera and BALF were detected by ELISA method in 24 hours after bursting.Results The concentration of TNF-α in sera (353.30±166.86 ng/L) of rabbits in therapy group were significantly lower than those in injury group (552.30± 169.64 ng/L;t=2.645,P =0.016).The concentration of NE in sera (63.40 ± 36.09 ng/ml) were lower than that of rabbits in injury group (97.60 ± 36.20 ng/ml;t=2.116,P=0.049).At the same time the concentration of NE in BALF (102.10± 9.50 ng/ml) of rabbits in therapy group were significantly lower than those in injury group (136.70± 13.60 ng/ml;t=6.593,P=0.000).Conclusion The expression of TNF-α in sera and NE in sera and BALF in rabbits with acute lung injury interposed by XueBiJing in underwater explosion were lower than those of injury group.

Clinical analysis of pediatric Langerhans cell histiocytosis involving the thyroid gland in 8 cases / 中华实用儿科临床杂志

Objective To explore the clinical features of Langerhans cell histiocytosis (LCH) involving the thyroid gland in children,in order to improve the diagnosis and treatment.Methods The clinical and imaging manifestations,thyroid function,treatment and prognosis of hospitalized children with LCH involving the thyroid gland in Beijing Children's Hospital,Capital Medical University,from July 2007 to July 2016 were analyzed retrospectively.Results In total 556 cases with LCH were analyzed,among which 8 cases (1.44％) were with LCH involving the thyroid gland.The onset age of children with LCH involving the thyroid gland was significantly older than the others with significant difference (average onset age:7.6 vs.3.4 year old;t =2.748,P =0.006),while the sex distribution showed no significant difference (1.67 ∶ 1.00 vs.1.38 ∶ 1.00;x2 =0.064,P =0.799).All 8 cases were Group Ⅰ,complicated by multiple organ involvement with vital organs included.None of the 8 cases had significant clinical symptoms of hypothyroidism,and thyroid imaging abnormalities were found in all 8 cases,including goiters and low echoes with irregular shapes,while 5 cases had subclinical hypothyroidism.All 8 cases were given the first-line standard chemotherapy for LCH-Group Ⅰ.Three cases without subclinical hypothyroidism showed good treatment effects and were assessed as non-active state and had already quitted medication.Five cases complicated by subclinical hypothyroidism had unsatisfactory treatment effects,among which 1 case abandoned treatment and 4 cases were adjusted for the second-line standard chemotherapy (Prednisone + Vincristine + Cytarabine + Cladribine).Finally,1 out of 4 case was assessed as non-active state after 3 months of medicine withdrawal,the other 3 cases were still in maintenance therapy.Conclusions LCH involving the thyroid gland is extremely rare,with significantly older onset age,and easily complicated by multiple organ involvement with vital organs included.Patients have no significant clinical symptoms of hypothyroidism,while some have subclinical hypothyroidism.The major imaging changes are goiters and low echoes with irregular shapes.Those LCH involving the thyroid gland complicated by subclinical hypothyroidism turn out to have poor prognosis,but Cladribine and Cytarabine are possible to improve the prognosis of such patients.

Clinical analysis of 112 patients with single-system Langerhans cell histiocytosis / 中华实用儿科临床杂志

Objective To investigate the clinical characteristics,treatment and prognosis of single-system Langerhans cell histiocytosis (LCH) in children.Methods A retrospective analysis was performed in single-system LCH patients registered between January 2006 and December 2012 in Beijing Children＇s Hospital Affiliated to Capital Medical University.The patients were divided into 2 groups:the bone involvement group and the other organ involvement group.The patients were assessed at 5 weeks,11 weeks,25 weeks,3 months,6 months,1 year and 3 years.The data were analyzed by using SPSS 17.0 software.Results A total of 112 patients (66 boys and 4,6 girls) with a median age of 5 years at diagnosis of LCH were analyzed.The most frequently affected organ was the bones(91 cases,81.3％),followed by skin(15 cases,13.4％).Few patients (27.6％) had acentral nervous system risk lesion,who were younger than those with other bone lesion(2.5 years vs 6.6 years).Patients with bone lesions were diagnosed at a significantly older age than other patients(5.6 years vs 1.5 years) (P ＜ 0.01).All patients received chemotherapy that included Prednisone and Vinblastine for 25 weeks.Twenty-five patients (22.3 ％) showed reactivation.Of these,4 patients exhibited reactivation in the pituitary.Three-year overall survival rate was expected to reach 100％,and no-event survival was expected at (73.22 ± 4.47) ％.Age of less than 2 years old was the factor of reactivation (P =0.033);sex,organ involvement and member of bone involved were not related with reactivation (P =0.679,0.142,0.639).Conclusions The bones were the frequent involvement organ in single-system LCH patients.These patients have a good prognosis.The rate of reactivation of single system-LCH can be decreased by chemotherapy.

Proved cases of drug-induced severe liver damage treated by Professor LI Ping / 中华中医药杂志

Liver-injury caused by chemicals is a common question in modern clinic. Professor LI Ping proposes ‘drug yellow’theory to guide TCM differential treatment. In this paper, the author will analyze the chemicals by the proved cases of drug-induced severe liver damage.