Objective:To investigate the clinical phenotype and prognosis among different genotypes of progressive familial intrahepatic cholestasis(PFIC) by cases analysis.Methods:The PFIC cases diagnosed at Beijing Children′s Hospital from 2015 to 2022 were collected, and the clinical phenotypic characteristics, treatment and prognosis were compared and analyzed.Results:A total of 628 cases of cholestatic liver disease were diagnosed, and 26 cases of PFIC were found, accounting for 4.1%.The number of PFIC 2 were the most, 14(53.8%)cases; three(11.5%) cases were PFIC 1; five(19.2%)cases were PFIC 3; while two(7.7%) cases were PFIC 4 and PFIC 6, respectively, and there was no case of PFIC 5.Type 1, 2, 4, and 6 had early onset ages(2 days to 21 months), while type 3 had a wide range of onset ages(8 to 145 months). The symptoms included jaundice(96.2%), pruritus(42.3%), and mucosal bleeding(15.4%). All three cases of type 1 had extrahepatic manifestations of diarrhea and malnutrition.Two cases of type 3 were found to have end-stage liver disease.Cases of PFIC 3 had increased serum γ-glutamyltransferase(97.2-439.5 U/L), while those of other types were normal.The bile acids were all increased(10.1-599.6 μmol/L). Abdominal ultrasound mainly showed liver enlargement(80.8%)and enhanced echogenicity of liver parenchyma(73.1%), enlargement of the spleen(61.5%). Ultrasound liver elastography ranged from 6.3 kPa to 23.1 kPa, there were 21(80.8%) cases ≥9 kPa.Among 26 cases, one case was lost to follow-up, and 11 cases were effective by oral medication alone.Fourteen children were still suffering from relapse or progress after drug treatment: four cases received liver transplantation (three cases had a good prognosis and one case died), two cases received biliary drainage, six cases were still taking drugs orally, and two cases died without active intervention in disease progress.Conclusion:Type 2 is the most common type in PFIC.The onset of most cases is in infancy.Jaundice, pruritus and hepatosplenomegaly are common clinical manifestations, and extrahepatic manifestations can be seen in type 1 cases.Type 3 cases can start with end-stage liver disease.Bile acid of all cases are increased.Except for type 3, the serum γ-glutamyltransferase of cases are normal.Oral medication has certain effects on some cases, but more than half progress, and some need biliary diversion or liver transplantation.

Objective:To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences.Methods:Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well.Results:A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions:There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

Objective:To investigate the efficacy of low-dose uric acid oxidase in treating children with aggressive mature B-cell non-Hodgkin lymphoma accompanied by hyperuricemia.Methods:Clinical data of children with primary aggressive mature B-cell non-Hodgkin lymphoma and hyperuricemia, who were treated in Beijing Children′s Hospital, Capital Medical University from January 2016 to June 2021 were retrospectively analyzed.The serum uric acid concentration was monitored in all pediatric patients from the day before chemotherapy to the seventh day of chemotherapy.Low-dose uric acid oxidase [0.05-0.10 mg/(kg·dose)] was intravenously injected into the patients when the serum uric acid level exceeded the upper limit of the normal range.The therapeutic effect and clinical medication experience of uric acid oxidase were summarized.The change of serum uric acid levels with time before and after the application of different doses of uric acid oxidase was analyzed by a repeated measures ANOVA. Results:A total of 106 children with primary aggressive mature B-cell non-Hodgkin lymphoma and hyperuricemia were enrolled in this study.There were 88 males and 18 females, with a median age of 6.5 (3.5, 10.0) years.The pathological subtypes comprised Burkitt′s lymphoma in 95 cases (89.6%), high-grade B-cell lymphoma in 7 cases (6.6%), and diffuse large B-cell lymphoma in 4 cases (3.8%). Additionally, 39 cases (36.8%) were in clinical stage Ⅲ and 67 cases (63.2%) were in stage Ⅳ.All cases had high tumor burden, including renal involvement in 52 cases (49.1%), tumor lysis syndrome in 42 cases (39.6%), and acute kidney injury in 27 cases (25.5%). Totally, one dose of uric acid oxidase was intravenously injected into 41 children (38.7%), 41 children (38.7%) were given 2 dosages, 20 children (18.9%) were given 3 dosages, and 4 children (3.8%) received 4 dosages.Moreover, 9 cases (8.5%) were supplemented with continuous renal replacement therapy.Serum uric acid concentrations before chemotherapy and 12 hours after injecting the first dose of uric acid oxidase were (741.4±312.9) μmol/L and (210.8±148.6) μmol/L, respectively.The difference was statistically significant ( t=5.288, P<0.001). The change of serum uric acid levels over time before and after the application of different doses of uric acid oxidase in children was compared, and no significant difference was found ( F=0.225, P=0.879). No delay in chemotherapy or death arising from tumor lysis syndrome and acute kidney injury occurred within 28 days after chemotherapy. Conclusions:Low-dose and on-demand application of uric acid oxidase can rapidly and effectively reduce serum uric acid levels in children with aggressive mature B-cell non-Hodgkin lymphoma in the early stage of chemotherapy.

Objective:To analyze the public demands for information about congenital birth defects in “Baidu zhidao” based on word frequency retrieval.Methods:Based on discussion between obstetrics and gynecology experts and epidemiological experts, the key words related to congenital birth defects were determined and the search strategy was formulated. Python 2.7 was used for web crawler search. Questions related to congenital birth defects were obtained on the “Baidu zhidao” platform, and then the R 4.0.2 software was used to process the data, complete the semantic analysis of keywords and statistical analysis of word frequency, and draw word cloud graph and polar chart to describe the key results.Results:A total of 16668 non-repetitive questions were retrieved from “Baidu zhidao” platform, and the frequency of semantic words was 15 371. Among them, 35.02% were the names and symptoms of congenital birth defects. In addition, the frequency of congenital heart disease was the highest (26.09%). The results of subject analysis of key words of birth defects showed that the average word frequency of diagnosis and treatment semantic words (49.55) was significantly higher than that of etiology and prevention semantic words (12.47). In addition, the key words of examination, cause, treatment, development and heredity were more frequently used in the semantic words related to the seven types of systemic malformations.Conclusion:The public in China has a high demand for information on congenital birth defect related diseases, and their causes, prevention and treatment, especially congenital heart disease.

Objective:To analyze the application for and funding for individual key clinical specialties under the Youth Program at the approved hospital groups, for suggestions on future development of hospitals.Methods:Based on the Youth Program data of the applications and approval as summarized by Beijing Hospitals Authority from year 2015 through 2018, 22 municipal hospitals were classified into three groups with more, less and none key clinical specialties respectively(the more group, the less group and the non group for short). The categories were made according to the number of state key clinical specialties approved by National Health Commission and key specialties approved by the National Administration of Traditional Chinese Medicine. χ2 test was used to compare the baseline situation, the approval rate of project applications, and the categories of approved project among the three hospital groups. Results:During 2015—2018 period, the number of applicants for Youth Program was 1 128 persons/cases. The groups with more, less, and none key clinical specialties were 7, 10, 5 respectively. In the more specialties group, the applicants of seniority less than five years accounted for 40.93%, who had higher than those of the other two groups( χ2=13.794, P=0.032), and higher doctoral degree applicants(80.31%) as well. The difference was statistically significant( χ2=116.611, P<0.001). The approval rate of the Youth Program in 2015—2018 in the group with key clinical specialties vs. the group with none key clinical specialties was 36.09%(166/460) rersus. 29.04%(194/668) with significant difference( χ2=6.222, P=0.013). The approval rate of the departments with more key clinical specialties was 37.82%, higher than those of less and none key clinical specialties(approval rate at 31.82% and 21.50%, respectively), with significant difference( χ2=16.897, P<0.001). However, there was no significant difference between the approval rates of key specialties group and non-key specialties in each hospital group( P>0.05). Of the three groups, the proportion of clinical medical projects in each group was all higher than such other types as scientific research, medical technology, hospital administration and nursing. Conclusions:The applications and approval rate of key specialties under the Youth Program were higher than the rest, reflecting the discipline advantage. At the same time, it can play an important leading role in the construction of research-oriented hospitals. It is necessary to further strengthen the showcase role of specialties, for encouraging innovative talents cultivation of other specialties, in the hope for promoting the construction of research-oriented hospitals in their clinical, scientific research, medical technology, management and nursing comprehensively.

Objective:To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China.Methods:The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated.Results:A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs.Conclusions:The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Post-marketing vaccine safety surveillance, including both passive and active surveillances, aims to detect and alert to signals of adverse events following immunization (AEFI), and to further ensure public safety and public confidence in vaccination. Active surveillance could proactively seek information of AEFI and timely investigate the potential safety signals, therefore, it has become the main development trend of post-marketing surveillance worldwide. Nowadays, there is an ongoing interest in developing active surveillance systems that can incorporate and use existing electronic data such as administrative claims and electronic health records. Researchers have also began exploring ways of accruing data closer to "real-time" in order to speed the recognition of potential safety problems.This near real-time vaccine safety surveillance is gradually emerging worldwide. This study reviews the development and methodology of near real-time surveillance and aims to accelerate the foundation of the active surveillance system for vaccine safety in China.

Objective:To investigate the basic information and implementation of medical assistance for children of illness-caused poverty families.Methods:From March through September 2019, a customized questionnaire was used to collect by means of both field survey and on-site verification, the information of the sick children from such families registered on file from 17 counties in 6 provinces. These counties were the first to carry out the assistance pilot work under " Chinese Children Poverty Alleviation by Healthcare Program" . The data so acquired were subject to descriptive analysis.Results:A total of 312 questionnaires were recovered, and the median age of these child patients was 8.54 years. Diseases causing family poverty were mostly those in the circulatory system, nervous system, neoplastic disease of childhood and hematological disease, while unaffordability of medical bills ranked the top challenge when they seek medical services. Hierarchical diagnosis and treatment was made for 251 children: 193(76.89%)of them could be admitted to provincial or lower medical institutions, 43 children needed chronic disease management, and 15 children needed to be admitted by the National Children′s Medical Center for further diagnosis.Conclusions:The assistance for such families in poverty-stricken areas can be upgraded, by such means as disease prevention publicity and education, publicity of healthcare poverty alleviation policy awareness, improvement of medical competency of primary medical institutions and rational application of medical resources.

Objective To explore the significance of the initial clinical symptoms and clinical manifestations of neuroblastoma(NB)to achive early identification of NB. Methods A retrospective study was performed on patients diagnosed with NB,who attended the Hematology Oncology Center,Beijing Childrenˊs Hospital from March 31st ,2007 to March 31st,2015. The clinical characteristics were compared between the children 〈1_year_old and≥1_year_old. The result was analyzed to compare the difference in clinical symptoms and tumor biologic characteristics of patients with different initial clinical symptoms between 2 groups. Results A total of 330 patients were included in the study,43 of them were younger than 1 year old,and their most common symptoms were cough and fever( each 17 cases,and accounted for 39. 5%,respectively);while the most common symptoms in patients≥1_year_old(287 cases)was fe_ver(177 cases,61. 7%),followed by lymphadenopathy(107 cases,37. 3%),bone pain(97 cases,33. 8%)and anemia (48 cases,16. 7%). The frequency of symptoms differed significantly between 2 groups(all P〈0. 05),such as fever (39. 5% vs. 61. 7%,χ2 ﹦6. 68),anemia(4. 7% vs. 16. 7%,χ2 ﹦6. 00),bone pain(0 vs. 33. 8%,χ2 ﹦18. 99),abdo_minal pain(0 vs. 25. 3%,χ2 ﹦10. 19),diarrhea(16. 3% vs. 3. 0%,χ2 ﹦12. 73),lymphadenopathy(7. 0% vs. 37. 3%, χ2 ﹦14. 12)and anorexia(9. 3% vs. 33. 4%,χ2 ﹦9. 21). Datients had fever,anemia,lymphadenopathy,cutaneous hemorrhagic spot or periorbital ecchymosis,bone pain,abdominal pain,exophthalmos,and anorexia early in the initial course of the disease,whose serum lactate dehydrogenase values were significantly increased(P〈0. 05). Datients suf_fered from fever,anemia,lymphadenopathy,bone pain,limbs dysfunctions,abdominal pain at the beginning of the disease,whose urine vanillymandelic acid values were higher than normal(P〈0. 05). Conclusions The study of sympto_mology suggests the most common symptoms in patients with NB 〈1_year_old are cough and fever,while those ≥1_year_old are fever,lymphadenopathy,bone pain,and anemia. Por patients with symptoms mentioned,carrying out the necessary NB_diagnose_related laboratory and imaging studies was statistically relevant to patientsˊ ages(〈1_year_old and≥1_year_old),which may contribute to earlier identification and diagnosis of NB.

Objective To evaluate the effect of an emollient containing Prinsepia utilis Royle oil extracts and other extracts on clinical symptoms and disease recurrence in children aged 2-12 years with atopic dermatitis (AD) in the remission period.Methods A multicenter,randomized,parallel-group,controlled clinical trial was conducted from December 2017 to September 2018.A total of 297 children aged 2-12 years with moderate AD were enrolled from 5 hospitals in China,and randomly divided into the test group (148 cases) and control group (149 cases).In the acute stage,the two groups were both topically treated with mometasone furoate cream once a day on the skin lesions,and with an emollient containing Prinsepia utilis Royle oil extracts and other extracts twice a day throughout the whole body for 2-4 weeks.The children would be enrolled into the remission stage if their Investigator's Global Assessment (IGA) score was ≤ 1 at following visits.In the remission stage,the test group was only topically treated with the emollient twice a day throughout the whole body,while mometasone furoate cream and the emollient were both withdrawn in the control group.At weeks 4,8 and 12 in the remission stage,the recurrence of AD,eczema area and severity index (EASI),children's dermatology life quality index (CDQOL) and adverse events were evaluated.Statistical analysis was carried out with SAS 9.4 software by using t test for comparison of normally distributed continuous data between two groups,chi-square test for comparison of unordered categorical data,Kaplan-Meier method for analysis of survival rates,Cox regression analysis for evaluating the effect of different therapies on AD recurrence in children in the remission stage,and Logistic regression analysis for analysis of odds ratio (OR) of EASI or CDQOL at week 4 in the remission stage between the test group and control group.Results Of the 297 children with AD,31 breached the clinical trial protocol,and 266 were included in the per protocol set (PPS),including 132 in the test group and 134 in the control group.In the PPS,114 and 106 patients completed the follow-up in the test group and control group respectively,and the recurrence rate was significantly lower in the test group (47,41.23％) than in the control group (84,79.25％;x2 =32.96,P ＜ 0.001).The time to recurrence was significantly longer in the test group(61.99 d ± 2.80 d)than in the control group(39.17 d ± 2.54 d,t =6.03,P ＜ 0.001),and the recurrence risk was significantly lower in the test group than in the control group (Log rank test,x2 =32.02,P ＜ 0.001).After adjustment for age and gender,Cox regression analysis showed that the recurrence risk in the test group was 0.35 times that in the control group (HR =0.35,95％ CI:0.24-0.51,P ＜ 0.01).At week 4 in the remission stage,the EASI score at P50-P75 and P75-P100 in the test group were 0.42,0.25 times that in the control group respectively (95％ CI:0.20-0.86,0.12-0.54 respectively;P =0.02,＜ 0.01respectively).Moreover,the CDQOL score at P75-P100 in the test group was 0.33 times that in the control group (95％ CI:0.17-0.65,P ＜ 0.01).No significant difference in the incidence of adverse events was observed between the two groups (P ＞ 0.05).Conclusion Maintenance treatment with the emollient containing Prinsepia utilis Royle oil extracts and other extracts can markedly reduce the recurrence risk in AD children,improve clinical symptoms,and enhance the quality of life.