Main causes of aplastic anemia misdiagnosed as immune thrombocytopenia in children / 中华实用儿科临床杂志

Objective:To explore the main causes of 50 children with aplastic anemia misdiagnosed as immune thrombocytopenia(ITP), summarize differential diagnosis experience, and provide clinical reference.Methods:According to the diagnostic criteria of aplastic anemia and ITP in children, the initial data of misdiagnosed cases in other hospital admitted to the Department of Pediatrics, Shanghai Tongji Hospital from January 2007 to December 2020, and the results of their re-examination tests in this hospital were analyzed.The causes of misdiagnosis and the main points of differential diagnosis were summarized.Results:Of the 165 children with aplastic anemia treated in the same period, 50 cases (30.3%) had been misdiagnosed as ITP.The main causes of misdiagnosis were summarized as follows.(1) The clinical manifestations in 22 cases disagreed with " typical symptoms of ITP" , and necessary bone marrow examinations were not performed in accordance with the international guidelines to confirm the diagnosis.(2) The bone marrow test results were interpreted falsely.Among 28 patients who underwent the bone marrow smear examination, 6 cases (21%) showed typical aplastic bone marrow, but they were still misdiagnosed with ITP.(3) Patients (15/28 cases, 54%) with atypical bone marrow smears did not receive further bone marrow biopsy to facilitate the diagnosis.(4) In 7 cases (7/28 cases, 25%), their bone marrow examination results met the diagnostic criteria of ITP at initial diagnosis, but no necessary review was performed to verify and correct the diagnosis after glucocorticoid trea-tment failed.Conclusions:Clinical diagnosis should be made in restrict accordance with related disease diagnostic criteria to avoid empirical errors.Diagnosis of ITP requires caution.Especially for those with atypical clinical manifestations or irresponsive to first-line drugs, bone marrow examinations (bone marrow biopsy if necessary) must be performed, and the test results should be correctly interpreted according to the diagnostic criteria to prevent clinical misdiagnosis or missed diagnosis.

Study on the relationship between blood concentration and efficacy of voriconazole in the treatment of pediatric invasive fungal infection / 药学实践杂志

Objective To explore the correlation between dose, blood concentration and efficacy of voriconazole in the treatment of invasive fungal infection in children. Methods 68 children treated with voriconazole during January 2019 to December 2019 were collected. The plasma concentration of voriconazole was assayed by high performance liquid chromatography (HPLC). The correlation between blood concentration and clinical efficacy was statistically analyzed. Results Different drug blood concentrations were obtained with different dosages: <4.0 mg/kg (6 cases) with the trough concentration ranged from 0.4 to 3.31 μg/ml (r=0.613, P=0.195). (4.0 - 7.0) mg/kg (44 cases), ranged from 0.35 to 7.02 μg/ml (r=0.325, P=0.018); >7.0 mg/kg (18 cases), ranged from 1.46 to 12.45 μg/ml (r=0.584，P＜0.023). There was a difference between the three groups (F=7.270, P=0.026). The relationship between the drug blood concentration and the therapeutic effect was obvious. In the <1.0 μg/ml group of 14 cases, 10 cases (71.4%) were effective, and 4 cases were ineffective. In the 1.0 - 5.5 μg/ml group of 48 cases, 44 cases (91.7%) were effective, and 4 cases were ineffective. In the >5.5 μg/ml group of 6 cases, 4 cases (66.7%) were effective and 2 cases ineffective. The difference among the three groups was obvious (χ2=5.360, P=0.039). Among the 68 cases, 58 cases (85.3%) were effective, and 10 cases (14.7%) were ineffective. Adverse reactions occurred in 10 cases (14.7%) with mild liver function injury, which did not affect the treatment and recovered with liver protection treatment. Conclusion This study showed that voriconazole was generally safe and effective in the treatment of invasive fungal infections in children. There was a significant dose-blood concentration and efficacy correlation. Further studies on pharmacokinetics and efficacy should be carried out to optimize the individualized treatment.

Advances on erythropoietin treatment of anemia in prematurity infants / 中华实用儿科临床杂志

Anemia is one of the common complications in preterm infants.Although there are many factors that can cause anemia of prematurity (AOP),erythropoietin (EPO) deficiency is one of the main causes of AOP.Insufficient EPO levels in premature infants and their mechanisms are the hotspots of AOP research at home and abroad.The rational use of EPO for prevention and treatment of AOP has become an international consensus and significant clinical outcomes have been obtained.The recent progress in the field of AOP,the relationship between EPO and AOP,and the clinical application and efficacy of EPO in the prevention and treatment of AOP in recent 3 to 5 years have been reviewed.

Advances on erythropoietin treatment of anemia in prematurity infants / 中华实用儿科临床杂志

Anemia is one of the common complications in preterm infants.Although there are many factors that can cause anemia of prematurity (AOP), erythropoietin (EPO) deficiency is one of the main causes of AOP.Insufficient EPO levels in premature infants and their mechanisms are the hotspots of AOP research at home and abroad.The rational use of EPO for prevention and treatment of AOP has become an international consensus and significant clinical outcomes have been obtained.The recent progress in the field of AOP, the relationship between EPO and AOP, and the clinical application and efficacy of EPO in the prevention and treatment of AOP in recent 3 to 5 years have been reviewed.

Mechanism of L-asparaginase resistance in chiIdren with acute IymphobIastic Ieukemia / 中华实用儿科临床杂志

F-asparaginask(F-LSP)is onk of thk cke agknts in thk long-tkrm chkmothkrape of lemphoid malignanciks in childrkn with acutk lemphoblastic lkuckmia(LFF)and non Hodgcin＇s lemphoma(NHF). If F-LSP rksistanck occurs in patiknts,it is highle suggkstivk of poor prognosis. Thkrkfork,thk mkchanism of F-LSP rksistanck is a major stude in thk fikld of diagnosis and trkatmknt of lkuckmia in childrkn. Ovkr thk ekars,rklatkd studiks havk shown that thk bask lkvkl of asparagink senthktask in tumor cklls,bonk marrow hkmatopoiktic support cklls,somk advkrsk mkta-bolic changks aftkr F-LSP chkmothkrape,and thk F-LSP silkncing inactivation induckd be sklf nkutralizing antibode can lkad to F-LSP rksistanck. In this papkr,according to thk litkraturk rklatkd rkports in rkcknt ekars,providk rkfkrknck for domkstic collkaguks,in ordkr to carre out thk rklkvant basic and clinical rkskarch,to providk thkorktical basis for thk rkalization of individualization of chkmothkrape.

Negative regulation of microRNA - 9 by ecotropic viral integration site1 involved in the pathogenesis of acute myeloid leukemia / 中华实用儿科临床杂志

Objective To investigate the regulation mechanism of microRNA - 9(miR - 9)by ecotropic viral integration site1(EVI1)its impact on proliferation of AML cells and its role in the pathogenesis of myelogenous leuke-mia. Methods EVI1 was forced to express in Uocm1 cell lines by murine stem cell virus - EVI1(MSCV - EVI1) plasmid infection. EVI1 overexpressed Uocm1 cells were then treated with 0. 1 μmol/ L 5 - aza - 2′ - deoxycytidine (5 - AZA)dissolved in dimethyl sulfoxide (DMSO). The methylation level of miR - 9 promoter was tested by DNA bi-sulfite sequencing technology. The cell cycle was observed by flow cytometry (FCM). The proliferation ability of the cells was detected by the colony forming assay in semi - solid Methylcellulose medium culture. Results EVI1 level was dramatically increased after being infected by MSCV - EVI1 plasmid. Forced expression of EVI1 in Uocm1 signifi-cantly downregulated miR - 9 by inducing hypermethylation of miR - 9 promoter. Relative expression level of miR - 9 was lower in EVI1 overexpressed group(0. 004 ± 0. 000)than that of the control group(0. 006 ± 0. 001)(t = 4. 09,P <0. 05). When EVI1 was overexpressed in Uocm1,the rate of G0 / G1 cells decreased markedly(P < 0. 05),while rates of S phage and G2 phage increased significantly(all P < 0. 05). Seven days after 500 cells plated in semi - solid medium, EVI1 overexpressed Uocm1 cells gave rise to more colony (122. 3 ± 7. 8)than Uocm1 cells infected with vector (45. 7 ± 6. 1)(t = - 13. 44,P < 0. 01). 0. 1 μmol/ L 5 - AZA recovered miR - 9 expression(P < 0. 01)by decreasing EVI1 induced hypermethylation of miR - 9 promoter. G0 / G1 phase cell proportion was(48. 25 ± 2. 19)％ in control group,while (65. 90 ± 2. 90)％ in 5 - AZA group (t = - 6. 85,P < 0. 05). 5 - AZA group formed less colony (51. 00 ± 10. 01)than the control group (123. 40 ± 8. 12)(t = 9. 59,P < 0. 01),which indicated that 5 - AZA inhibi-ted cell proliferation by G0 / G1 cell cycle retardation in EVI1 overexpressed uocm1 cells. Conclusions EVI1 may en-hance proliferation ability of myeloid leukemia cells by downregulating miR - 9 through inducing hypermethylation of miR - 9 promotor,which plays a crucial role in the pathogenesis of AML. 5 - AZA may be an effective hypomethylating agent in the therapy of EVI1 high acute myeloid leukemia.

Progress of predicting response to immunosuppressive therapy in aplastic anemia / 中华实用儿科临床杂志

Aplastic anemia is a severe hematological disease characterized by bone marrow failure and pancyto-penia.Immunosuppressive therapy(IST)with antithymocyte globulin(ATG)and cyclosporine A(CSA)is the first -line treatment for patients who lack an HLA -matched sibling.One third of the patients has no response to IST and the high risk of ATG -related adverse effects may lead to ATG -related death.So it is necessary to explore the predictive marker of response to IST.A defined predictive marker may make the selection of treatment more reasonable and further improve the long -term efficacy.The relevant literatures were analyzed and summarized in recent years,in order to pro-vide a reference for clinical treatment and a baseline for prospective studies.

Diagnosis and treatment of dyskeratosis congenita in Chinese children / 中华实用儿科临床杂志

Objective To analyze and summarize the characteristics of Dyskeratosis congenita(DC)in Chinese children,so as to provide reference for early diagnosis and reasonable prevention and treatment of DC.Methods The data collected from 43 cases with DC in the domestic literature in recent 10 years,as well as the clinical data of 2 cases with DC treated at Tongji Hospital,Medical School,Tongji University,and a total of 45 cases with DC were analyzed and compared with those reported in the literatures of foreign countries.Results Based on the detailed data of 2 typical cases at Tongji Hospital,Medical School,Tongji University,and the data of 45 cases in China were summarized,so the major differences in the main characteristics of DC between Chinese Children and the foreigners were as follows:(1)Onset were earlier(mean age 4.5 years,median age of 3 years),but the diagnosis was delayed(mean age of 17.9 years,median age of 18 years).(2)The presence of skin pigmentation,nail lesions and mucosal leukoplakia,such as the proportion of the complete DC triad was higher(42/45 cases,93.3％).(3)There was an earlier onset of hematopoietic suppression(mean age 5.6 years).(4)Telomerase related gene mutation types were relatively minor,DKC1(7 cases)and TINF2(6 cases)were reported in recent years,and no other type of mutation was found.(5)Effective therapy of hematopoietic reconstitution was administered in 2 cases after allogeneic hematopoietic stem cell transplantation(allo-HSCT).The effective rates were about 70％(7/10 cases)in treating bone marrow failure with low dose androgen and low dose glucocorticoid.Conclusions DC is very common in infants in China,the clinical manifestations of triad are more typical,but the age of diagnosis was significantly delayed.Improving the understanding of DC and combination with the detection of related gene mutation may improve the early diagnosis rate and clinical efficacy with allo-HSCT or effective drug maintenance therapy,and also provide reference for propitious familial eugenics and prenatal examination.

Prediction and early diagnosis of type 1 diabetes mellitus in children / 中华实用儿科临床杂志

Type 1 diabetes mellitus(T1DM) is one of the most common chronics autoimmune disease of childhood with no effective prevention and curative treatment.Improving clinical understanding of the pathogenesis and onset of T1 DM in children,improving the rate of pre-diagnosis,carrying out effective clinical intervention timely is one of the hot fields in diagnosis and treatment of diabetes in children.This paper will make a review of domestic and international literature of the recent 3 to 5 years.

Efficacy of different doses of intravenous immunoglobulin in the treatment of severe aplastic anemia / 临床儿科杂志

Objective To analyze the efficacy of different doses of intravenous immunoglobulin (IVIG) in the treatment of acquired severe aplastic anemia (AA) in children. Methods The clinical data of hospitalized children with severe AA who received adjuvant immunosuppressive therapy of IVIG from January 2000 to December 2015 were retrospectively analyzed. According to different doses of treatment, the children were divided into low dose group ( IVIG 200-400 mg/ (kg·d) once every 4 weeks for 6 times), high dose group (IVIG 1 g/ (kg·d ) x 2 days once every 4 weeks for 6 times). Results All the children were followed up until December 31, 2015. Among the 61 children, it was effective in 41 children and total effective rate was 67.2%. The effective rate of anti thymocyte globulin (ATG) treatment in high dose group was higher after 3 months than that of low dose group, and there was statistical difference (P=0.020). The interval between first dose of IVIG and first dose of ATG in 20 cases of ineffectiveness was 2.0 (2.0-5.0) d, while that in 41 cases of effectiveness was 8.0 (7.0-9.0) d, and the difference is statistically significant (P<0.001); Among the 20 ineffective children, 18 children had the interval <7 day. The survival rates of the two groups were 80% and 87.1%, respectively, and there was no difference between two groups (P>0.05). The incidence of severe infections in the high-dose group was lower than that in the low-dose group after the use of ATG for 6 months, and there was statistical difference (P=0.008). Conclusions High dose of IVIG therapy can increase the early response rate in children with acquired severe AA, but it does not increase the long-term effectiveness, cure rate and 5 year survival rate. In addition, it can reduce the severe infection rate, but cannot reduce the total infection rate and infection related mortality rate.

Implementation and effectiveness of the construction of the demonstration ward in pediatric clinical practice teaching / 中华医学教育探索杂志

Department of Pediatrics of Tongji Hospital Affiliated to Tongji University, through med-ical school practice teaching demonstration ward construction project, obtained remarkable achievements in perfecting project construction plan, paying attention to the implementation of project tasks and improving the teaching quality and personnel training, and in improving the teaching quality of the sustainable devel-opment condition and so on.

"Understanding and practice of ""the Chinese expert consensus for the diagnosis and treatment of childhood myelodysplastic syndromes""" / 中华实用儿科临床杂志

Childhood myelodysplastic syndromes(MDS) is a disease with lower incidence and very difficult in clinical diagnosis and treatment.The Chinese expert consensus for the diagnosis and treatment of childhood myelodysplastic syndromes recently recommended by Subspecialty Group of Hematology,the Society of Pediatrics,Chinese Medical Association,is a high academic significance of guidance documents to improve the efficacy of diagnosis and treatment,as well as relevant research of children with MDS in our country.This paper combined with the relevant lite-rature review at home and abroad in recent years and summed up the experience of clinical diagnosis and treatment,in order to contribute the promotion of this consensus of the experts.

Recent progeress of pathogenesis in acquired aplastic anemia He Wei,Xie Xiaotian / 中华实用儿科临床杂志

Aplastic anemia (AA)is a serious disease of hematological malignant disease in children.Severe AA is difficult to treat and may lead to high motality.Acquired AA accounts for 95% of all cases,so it′s significant to lucubrate the pathogenesis of acquired AA for clinic diagnosis and therapy.The documents in recent 5 years are collected,and a reviews about the progress of pathogenesis in acquired AA children is provided.

Clinical characteristics and management of children with Wiskott-Aldrich syndrome / 中华实用儿科临床杂志

Objective To improve the early diagnosis of Wiskott-Aldrich syndrome (WAS),through summing up and analyzing the clinical characteristics of children with WAS.Methods The clinical and laboratory characteristics of 18 children with WAS,including the cases from Suzhou Jiulong Hospital,Shanghai Jiaotong University School of Medicine,and Tongji Hospital Affiliated to Tongji University,and the domestic reports in recent 6 years,were induced and analyzed.Results All patients were males;the average of incidence age was about 1.9 months and the average age at diagnosis was 10.8 months.All cases had the clinical characteristics of WAS including eczema,infection tendency and thrombocytopenia with small platelet size.Moreover,10/18 cases (55.56％) WAS patients progressed to severe cases (scores reached to 4 or 5 points)at diagnosis,and with the increase of age of the patients at diagnosis,the ratio of severe cases would be increased.The conventional immune function indexes showed no specific diagnostic value,and the typical clinical features and the WAS gene mutation detection were the key diagnostic basis.Seven cases used to be misdiagnosed as idiopathic thrombocytopenia,and received corticosteroids and intravenous immunoglobulin therapy.In a total of 18 cases,4 cases received allogeneic hematopoietic stem cell transplantation,of which,β cases were cured and 1 case died of transplantation-related interstitial pneumonia,while the remaining 14 cases are unknown for their with follow-up treatment and prognosis.Conclusions The typical clinical features and the WAS gene mutation detection were the key diagnostic basis.In order to improve the rate of early diagnosis and avoid misdiagnosis,it's a great need to improve the clinical understanding of WAS.

The latest treatment advances of severe acquired aplastic anemia / 中华实用儿科临床杂志

Acquired aplastic anemia is a refractory blood disease for children,and severe acquired aplastic anemia can be a great threaten for life.China is a high incidengce area,children at a period during which this disease can mostly occur.In China,except some congenital aplastic anemia,most children who have this diease is acquired aplastic anemia.In 2009,the Britain society of hematology recommended Guidelines for the diagnosis and management of aplastic anaemia,which represented the latest diagnosis and treatment principle and mainstream view of the clinical methodology about aplastic anemia.They make it clear that the main treatment for the disease are allogeneic hematopoietic stem cell transplantation(allo-HSCT) and immunosuppressive therapy(IST).This article collects the documents in recent 5 years,and provides a overview about the latest advance of the allo-HSCT and IST in the word.

Percentage and functions of natural killer T cells in peripheral blood and bone marrow of children with severe aplas-tic anemia / 临床儿科杂志

Objective To analyze the percentage and functional changes of natural killer T (NKT) cells in peripheral blood and bone marrow of severe aplastic anemia (SAA) children before immunosuppressive therapy (IST) comparing to that of healthy children.Methods Ten children with severe aplastic anemia were included in the study and ten healthy children at the same age were selected as the control group. By lfow cytometry, the percentage of CD3+CD1d tetramer+ NKT cell in peripheral blood and bone marrow were detected from March 2014 to December 2014 in our hospital. Immune magnetic bead separation was used to isolate and purify iNKT cells .The puriifed iNKT cells were cultured in the OCH(50 ng/ml,100 ng/ml or 200 ng/ml)+rhIL-2+rhG-CSF culture systems. The ampliifcation of iNKT cells after cultured in different systems were calculated. Elispot method was used to analyze the spotting form cells (SFCs) of IFN-γ or IL-4 expressed by activated iNKT cells.Results The percentage of CD3+CD1d tetramer+ NKT cells in peripheral blood of SAA group(0.72±0.03)% was signiifcantly lower than that of the control group(0.92±0.02)%(P=0.000). The percentage of CD3+CD1d tetramer+ NKT cells in bone marrow of SAA group(0.82±0.02)% was signiifcantly lower than that of the control group(1.05±0.05)%(P=0.000).In vitro iNKT cell ampliif-cation ability of bone marrow in SAA group was signiifcantly lower than the control group, and in medium concentration(50±6) and high concentration OCH group(52±6), the ampliifcation ability was higher than that in low concentration OCH group(30±5) (P<0.05). The secretion of IFN-γ in the iNKT cells of SAA bone marrow was signiifcantly lower in medium concentration(33±3) and high concentration(35±3)OCH group than that of the low concentration(50±3)OCH group(P<0.01). The secretion of IL-4 in the iNKT cells of SAA bone marrow was signiifcantly higher in medium concentration(50±3)and high concentration(75±3) OCH group than that of the low concentration(33±3) OCH group(P<0.01).Conclusions The quantity and function of NKT cells from children with SAA are lower than that of the healthy children.In vitro, they had better ampliifcation ability and could improve IL-4/IFN-γ imbalance in medium concentration and high concentration OCH group than in low concentration OCH group.

Attention to the diagnosis and treatment for children with non-malignant hematological diseases / 临床儿科杂志

Based on the analysis of the recent possible problems of diagnosis and treatment in the ifeld of childhood hema-topoietic diseases, this paper provides a brief interpretation on recent recommendations or guidelines for children with non-ma-lignant hematological diseases issued by the Chinese Pediatric Hematology Group, including iron deifciency anemia, immune thrombocytopenia, hemophilia, beta thalassemia and aplastic anemia.

The practice and thinking on the standardized training of pediatric residents / 中华医学教育探索杂志

The standardized training for pediatric residents is a necessary route to promote their clinical ability and make them grow up.With the aim to improve the residents' basic theory,clinical skills and medical quality,we set up training plans according to the requirement of standardized training in shanghai,earnestly implement the related training in the process of training content,method,time node and stage appraisal system,formulating personalized training plan and implementing one to one teaching.Besides,we attach importance to the cultivation of scientific research and teaching ability of residents and set up a perfect evaluation system.Residents are required to obtain a certificate of training through the unified comprehensive examination before graduation.Here,the problems existing in the process of pediatric resident standardization training and preliminary countermeasures are also discussed.

Key points summarization of 《Guidelines for the diagnosis and management of aplastic anemia (2009)》 / 中华实用儿科临床杂志

Aplastic anemia (AA) is one of serious hematopoietic diseases,clinical diagnosis and treatment is difficult.The guidelines for the diagnosis and management of aplastic anemia recommended (Guideline) by British Society for Haematology Committee in 2009,is made up of many experts based on experiences,used the method of evidence-based medicine,and collected all the reports of diagnosis and treatment of AA published in recent years,after strict screening screening and sums up the writing complete guidance document represented the principle and clinical methodology of diagnosis and treatment of AA in the mainstream view of world.The Guideline is comprehensive,on the basis of fully,opinionated,detailed,clinical maneuverability is strong,has a very high refe-rence value.In this paper,that selected and summarized of the contents closely related to the clinical diagnosis and treatment of AA from the guideline,in order to provide reference well to the colleague.

Reform and practice of continuing medical education programs / 中华医学教育探索杂志

According to the principles on the continuing medical education by Ministry of Health and all the problems which may exist in continuing education classes currently held in our country,the author conducted in-depth thinking and meaningful reform practice in the following areas of teaching direction and content scope,teaching and class scale,teaching methods and examination system,etc.and summarized the experience and achievements in improving the quality of the continuing medical education and effective technology promotion,as well as the promotion of medical education career and subject construction development.