Objective:To analyze the clinicopathological features, treatment and prognosis of Epstein -Barr virus(EBV) positive diffuse large B cell lymphoma(DLBCL) in children, so as to improve the knowledge of pediatricians on this disease.Methods:The data of 6 cases of EBV positive DLBCL who were initially diagnosed and regularly treated in Beijing Children′s Hospital from January 2016 to December 2019 were collected, including basic information (gender, age, first symptom, and course of disease), pathological results [immunohistochemistry, EBV encoded RNA(EBER), latent membrane protein(LMP), and C- MYC gene], immune function, EBV index, treatment group, treatment plan and prognosis. Results:There were 4 males and 2 females, with the average age of 6.67 years.The uric acid was 266.2 μmol/L, lactic dehydrogenase(LDH) was 346.5 U/L at early stage, and 1 patient had immunodeficiency.The immune function test before chemotherapy indicated that the proportion of auxiliary T cells decreased in 4 cases, and the humoral immune function was normal in all patients.There was no evidence of recent infection in 6 patients, and EBV-DNA increased in 3 patients.There were 2 cases of stage Ⅲ, 4 cases of stage Ⅳ, 1 case of giant tumor, 2 cases of symptom B, 6 cases of extranodal invasion, 4 cases of central invasion and 1 case of bone marrow invasion.Three patients died and three survived.Immunohistochemistry showed that: (1) CD 19, CD 20, and CD 79a were expressed in all patients, and CD 30 was expressed in 5 patients.(2) C- MYC gene was detected by immunofluorescence in situ hybridization method in all patients, and no MYC break, Bcl-2 and Bcl-6 break and amplification were found.(3) EBV: EBER and LMP-1 were expressed in all patients. Conclusions:The pathological changes of EBV positive DLBCL are similar to those adults.The origin of non-germinal center and extranodal and central invasion are more common.The prognosis of the patients with central nervous system invasion is very poor, and the recurrence and progress of the disease often occur in the treatment or in the early stage of drug withdrawal.At present, there is no effective and feasible treatment plan.It is suggested that the patients in the late stage should receive allogeneic hematopoietic stem cell transplantation as soon as possible after intensive treatment, so as to improve the survival rate.

Objective To study clinical characteristics and prognostic factors in primary systemic anaplastic large cell lymphoma (S-ALCL). Methods Clinical data of 56 S-ALCL were retrospectively analysed, who were diagnosed in Lymphoma Lab of Peking University Health Science Centre. Immunohistochemical staining for ALK-1 and bcl-2 were performed by standard SP method. Results The median age of patients is 17 years, and the ratio of sex was1.67:1 (male : female) in 56 cases of S-ALCL. Among of the 49 cases who were followed up, 32.65 % (16/49) of patients died, and all of them died within two years after diagnosis. The 3-year and 5-year overall survival were 64.28 %. 41 out of 56 cases (73.21 %) was positive for ALK-1 protein, while 10 cases out of 56 S-ALCL cases (17.86 %) positive for bcl-2. Clinical staging, extranodal sites of involvement or with extranodal sites of involvement and ALK were important prognostic factors with statistic significance by Long-rank test. Among of them, Clinical staging was the most independent prognostic factor by COX multivariate analysis. Conclusion S-ALCL was mostly seen in the young and middle-aged male patients. The death were most frequently occurred within two years after diagnosis. Most of the patients who have good responses to chemotherapy can get the complete remission and long-term survival. Clinical staging, extranodal sites of involvement or with extranodal sites of involvement and ALK were very important prognostic factors which can be used to predict the patients long term survival, and guide the treatment.

Objective To investigate and analyse the status and influential factors of palliative care knowledge of nursing undergraduates,then provide theoretical basis for palliative care education. Methods Using random sampling method, 400 nursing undergraduates were investigated by Palliative Care Quiz for Nursing (PCQN) and palliative care attitude questionnaire. Results 366 nursing undergraduates completed the survey whose scores were 8.363 ± 4.240, and 66.9%(244/366) of them had never heard of palliative care. Choosed right rate of PCQN was 41.13% (150/366). The scores of palliative care philosophy and principles 0.298±0.248, pain and symptom control and psychological scores 0.436 ± 0.235 and social and spiritual support scores 0.499 ± 0.318 had significant difference (F=38.866, P=0.000). The scores of palliative care attitude questionnaire were 36.756 ± 3.183, and the average score of all items were over 3. The palliative care attitude scores had significant difference in different grade (F=2.737, P=0.043). Conclusions Nursing undergraduates hold positive attitudes of palliative care, but the cognition degree were at a low level. To promote the development of palliative care, it should be strengthened publicity, education and training in this area. It is necessary to carry out palliative care education in nursing undergraduate students.

Objective To investigate the immunophenotype and molecular genetics of mature aggressive B-cell lymphomas in Chinese pediatric patients and provide the criteris for the diagnosis of them.Methods We collected 97 paraffin-embeded tissue samples of pediatric cases of mature aggressive B-cell lymphomas including 81 Burkitt lymphoma (BL) cases, 8 diffuse large B cell lymphoma (DLBCL) cases and 8unclassifiable B cell lymphoma with featares intermediate between BL and DLBCL (BL/DLBCL) cases. The immunophenotype and genetic features of them were detected by immunohistochemistry and interphase FISH.Results The expression of bcl-2 [3 %(2/66) in BL, 50 % (4/8) in DLBCL, 50 % (4/8) in BL/DLBCL], MUM1 [17 % (12/71) in BL, 63 % (5/8) in DLBCL, 63 % (5/8) in BL/DLBCL] and mean Ki-67 proliferation index [(93±4.4)% in BL, (83±14.3)% in DLBCL, (80±11.5)% in BL/DLBCL] were significantly different between BL and DLBCL and between BL and BL/DLBCL. The frequency of c-myc rearrangement [98 % (79/81) in BL,38 % (3/8) in DLBCL, 50 % (4/8) in BL/DLBCL] and an extra copy of bcl-6 [0 % in BL, 38 % (3/8) in DLBCL, 25 % (2/8) in BL/DLBCL] were also significantly different between BL and DLBCL and between BL and BL/DLBCL. Conclusion Diagnosis of the mature aggressive B cell lymphomas in pediatrics should be based on the comprehensive review and integration of morphologic, immunohistochemical and molecular genetic features. BL/DLBCL is more likely a subgroup of the DLBCL in pediatric population. The expression of CD10 and bcl-6 but not bcl-2, a high Ki-67 PI (＞90 %) and a c-myc rearrangement but not bcl-2 or bcl-6rearrangement are the features of BL. Regardless of the expression of CD10 and bcl-6, positive staining for bcl2, Ki-67 PI below 90 % and an extra copy of the bcl-6 favor a diagnosis of DLBCL or BL/DLBCL.

Objective To study the expressions of anaplastic lymphoma kinase (ALK-1) and cytotoxic proteins in primary systemic anaplastic large cell lymphoma (S-ALCL) and their relationship with clinical outcome. Methods 51 S-ALCL cases were collected from Lymphoma Lab of Peking University Health Science Centre & Peking Children's Hospital. The morphologic characteristics were studied under routine microscope, and essential immunohistochemical stainings were performed and reviewed to confirm the diagnosis of S-ALCL. Immunohistochemical stainings for ALK-1 and cytotoxic proteins (TIA-1 & granzyme B) were performed using standard SP method. Patients related clinical data including follow-up materials were collected. Results Survival time of 44 cases with completely clinical follow up materials ranged from 0.5～66months. 36 out of 51 cases(37 %) was positive for ALK-1 protein. While 20 cases out of 47 S-ALCL cases ( 42.55 % ) positive for granzyme B and 22 out of 28 cases (81.48 %) were positive for TIA-1. The prognosis of patients with ALK-1 protein positive and granzyme B negative expression was better, but TIA-1 expression might have nothing to do with clinical outcome (P＞0.05). In addition, multivariate analysis confirmed that ALK-1 protein expression, granzyme B protein expression and Ann-Arbor stage system were possible for prognosis(P＜0.05), Conclusion Expression of ALK-1 and granzyme B protein expression may serve as two independent prognostic predictors in S-ALCL patients.

Objective: To review the clinical-pathology characteristics of 19 relapsed pediatric mature B cell lymphoma and to find the risk factors for recurrence and the feasible treatment after relapse. Method: Data of 212 pediatric B cell lymphomas cases in Beijing Children′s Hospital from January 2006 to June 2015 were collected retrospectively. All the patients were treated according to the B cell lymphoma regimen of Beijing Children′s Hospital. During the study period, 19 of 212 cases were relapsed; the clinio-pathological characteristics of relapsed patients before treatment and after relapse were analyzed retrospectively, the treatment outcomes after relapse were summarized and the patients were followed-up. Result: Nineteen of 212 cases had relapsed disease, for these relapsed patients: the median age at initial diagnosis was 5.5 years old, the median level of uric acid was 384(range, 121-713)μmol/L, the median level of lactate dehydrogenase(LDH) was 1 323(range, 146-6 370)U/L. Among 19 relapsed patients, 10 had local relapse and 9 had multiple relapses; 17 were Burkitt′s lymphoma and 2 were diffuse large B cell lymphoma. Staging: 2 cases were stageⅡ, 3 cases were stage Ⅲ and 14 cases were stage Ⅳ. Risk group: 6 cases were group B and 13 cases were group C. Nine cases had bone marrow involvement and 10 cases had central nervous system(CNS) involvement. Acute tumor lysis syndrome was seen in 6 cases during the early treatment and 13 cases had delayed treatment. Treatment after relapse: 10 cases received further treatment after relapse (rituximab + 1-4 courses high intensity second-line chemotherapy), 3 cases received autologous stem cell transplantation. There was no chemotherapy or infection related death, 3 cases achieved complete remission (CR). For all the 212 patients, the median follow-up time was 47 (range, 1-131)months and the 5-year event free survival(EFS)rate was (89.4±0.2)%. For the 19 relapse cases, the 5-year overall survival (OS) rate was (21.1±0.1)%, CR rate after relapse was 30%, patients died of the progression of the primary disease, no treatment related death occurred. Univariate analyses showed that bulky disease, stage Ⅳ, maxillofacial and CNS involvement, LDH>1 000 U/L, delay treatment, day 7 evaluation shrink <25%, residual diseases after 3 months treatment are relapse risk factors (all P<0.01). Conclusion Patients relapse during the treatment or at the early stage after the end of all chemotherapy have poor prognosis. So far there is no effective method for early relapse patients; the late relapse patients had the possibility of CR if they are sensitive to salvage treatment. In conclusion, to improve the outcome, the key point is to reduce the relapse.

Mechanical ventilation is an important supportive treatment for acute respiratory distress syndrome (ARDS). However, improper mechanical ventilation can cause a "second hit" to the lung, that is, ventilator-induced lung injury (VILI), characterized by translocation of pulmonary inflammatory mediators into the bloodstream, aggravating systemic inflammatory response syndrome, and multiple organ failure. Although the current protective mechanical ventilation strategy plays an important role in supporting treatment, the mortality of ARDS with mechanical ventilation is still very high. Therefore, to explore the strategy of pulmonary protective ventilation has always been the key orientation of ARDS and has important clinical significance. This article reviews the application, advantages and disadvantages of assisted and non-assisted spontaneous respiration in ARDS patients undergoing mechanical ventilation, in order to provide a reference for research and development of new strategies for ARDS protective ventilation.

Objective: To analyze the clinical features and prognostic factors of childhood Burkitt's lymphoma and to summarize the therapeutic effect of the mature B-cell lymphoma regimen of Beijing Children's Hospital. Methods: It was a retrospective study. From January 2007 to December 2015, 186 patients below 18 years of age with newly diagnosed, untreated Burkitt's lymphoma were enrolled. Three cases were eliminated because of the abandonment of the treatment and 183 cases were stratified and treated according to the mature B-cell lymphoma regimen of Beijing Children's Hospital, groups were as follows: A, n=1; B, n=59; C, n=123 and 97 patients in group C received combined rituximab therapy during the treatment. The clinical features and therapeutic effects of patients were analyzed, overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method. COX regression was used to identify the prognostic factors. Results: The median age at diagnosis was 5 (1-14) years. There were 159 males (85.5%) and 27 females (14.5%) , the male-to-female ratio was 5.9∶1. A total of 174 cases (93.5%) evolved to stage Ⅲ and Ⅳ. Eight cases did not achieve remission and progressed to death, 9 cases relapsed. Only 5 patients (2.7%) died of treatment-related complications. With a median follow-up time of 48.0 (0.5-128.0) months, the 5-year OS rate and EFS rate were (89.1±2.3) % and (87.8±2.5) %. There was significant difference in the 5-year EFS rate between group B and C ( (94.9±2.9) % vs. (84.0±3.4) %, χ²=4.258, P=0.039). The 5-year EFS rate was (73.1±8.7) % and (86.7±3.7) % for patients in the group C treated with chemotherapy only and those treated with chemotherapy combined rituximab, but no statistical difference was found between them (χ²=3.360, P=0.067) . Central nervous system (CNS) involvement, insensitivity to early phase chemotherapy, residual diseases in mid-term evaluation were independent unfavorable prognostic factors (HR=6.167, 9.102, 3.104, 95%CI: 2.293-16.592, 1.837-45.107, 1.182-8.153) . Conclusions The large dose, short course treatment of mature B-cell lymphoma regimen of Beijing Children's Hospital is effective for pediatric Burkitt's Lymphoma. Combined treatment with rituximab can improve the efficacy. CNS involvement, insensitivity to early phase chemotherapy, residual diseases in mid-term evaluation are associated with increased risk of poor prognosis.

Objective: To improve the awareness of methylmalonic acidemia and hyperhomocysteinemia with diffuse lung disease as an initial or main presentation. Methods: A retrospective analysis of the clinical manifestations, radiological features, laboratory tests, genetic variations, treatments and prognoses was conducted in six children presented with diffuse lung disease and finally diagnosed with methylmalonic acidemia and hyperhomocysteinemia in Ward 2 of Department of Respiratory Diseases, Beijing Children′s Hospital, from August 2017 to November 2018. Results: Six children were included in this study. Two children were male and four were female. The average age of onset was 28 months. The mean age at diagnosis was 34 months. The average interval from onset to diagnosis was 6 months. Four children who underwent genetic tests were found to have variants of gene MMACHC and diagnosed with CblC type. All children had respiratory symptoms and signs as initial or main presentation, which were tachypnea (5 cases), exercise intolerance (5 cases), cough (4 cases), cyanosis (4 cases), clubbing (4 cases), dyspnea (3 cases) and retractions (3 cases). Pulmonary arterial hypertension was found in all six children. Pericardial effusion (4 cases), kidney involvement (3 cases), nervous system involvement (3 cases), gastrointestinal system involvement (3 cases) and anemia (2 cases) also coexisted. The high resolution computed tomography (HRCT) features included dilated pulmonary artery (6 cases), ground-glass opacities (4 cases), diffuse poorly defined ground-glass centrilobular nodules (3 cases), pleural effusion (3 cases), thickening of interlobular septum (2 cases), etc. All children had an elevated concentration of methylmalonic acid in urine and homocysteine in plasma. Genetic tests were performed in four patients, and MMACHC genetic mutations were found in all of them. Clinical manifestations, HRCT features and pulmonary arterial hypertension turned better in five children after treatment. One patient who was not regularly followed-up died. Conclusions Pulmonary involvement including diffuse lung disease and pulmonary arterial hypertension could coexist with methylmalonic acidemia and hyperhomocysteinemia, which may have respiratory symptoms and signs as the initial or main presentation. Characteristic HRCT features were found in some patients. Plasma homocysteine test is a quick method for screening the disease in children with diffuse lung disease and (or) pulmonary arterial hypertension. Both diffuse lung disease and pulmonary arterial hypertension may turn better after treatment.

Objective: To summarize the clinical data of diffuse large B-cell lymphoma (DLBCL) in children and to evaluate the efficacy of Beijing Children′s Hospital B cell lymphoma protocol in the treatment of pediatric DLBCL. Methods: The data (clinical, pathology, lab and image data) of 46 pediatric DLBCL admitted to the treatment group of Beijing Children′s Hospital from January 2005 to June 2017 were collected and analyzed retrospectively. According to the risk factors of staging, existence of poor prognosis genes and giant tumors, stratified treatment was carried out according to the international standard modified LMB89 regimen with high dose and short course. The Kaplan-Meier method was used to calculate the event free survival (EFS) and the overall survival (OS). Results: (1) Among the 46 cases, there were 33 males and 13 females. The median age was 8.0 years. The time from the initial symptom onset to the diagnosis was more than 15 days in 45 children. Fourteen cases had B group symptoms (fever, night sweat, and weight lost), 25 cases had extranodal disease, 39 cases were stage Ⅲ and Ⅳ, 12 cases had bone marrow involvement, 3 cases had jawbone involvement. Thirty cases were group B and 16 cases were group C in the treatment group. (2) Initial symptoms: 6 cases had cervical mass, 20 cases had abdominal mass, 10 had abdominal pain with acute abdomen, 8 cases had fever, 2 cases had snore or upper respiratory tract obstruction. (3) Pathology result: 40 cases were germinal center B cell DLBCL, 6 cases were non germinal center B cell DLBCL, no case had the MYC gene rupture, double hit lymphoma and triple hit lymphoma. (4) Complication and evaluation: the tumor lysis syndrome was seen in 3 cases initially, severe infection and delayed treatment was seen in 1 case, no treatment related death. The first evaluation showed all cases were sensitive to chemotherapy (shrink>25%), the second evaluation showed 1 case had residual disease, the others were complete remission. (5) Treatment and outcome: the 5 year-EFS was the same with 5 year-OS, both were (97.8±2.2) %. Two cases relapsed after treatment off, early relapse was seen in 1 case, and died because of abandoning treatment. Late relapse was seen in 1 case and got a complete remission after Rituximab+group C protocol treatment. Conclusions Pediatric DLBCL was common in school aged boys, most cases were at middle and late stage at the time of diagnosis. DLBCL had a good prognosis after the treatment with Beijing Children′s Hospital′s B cell lymphoma protocol, but late relapse could be seen.