2018年 · 第56卷第09期

In recent years, clinical research has become more and more popular, and real-world research^[1]Registered studies^[2]Concepts such as cohort studies and cross-sectional studies are coming one after another. We seem to feel that the spring of clinical research is coming. Clinicians finally have a lot to do, but they are very confused. Clinical research is visible and intangible. What is clinical research and how should it be carried out? Clinical research? Since 2016, the author's team has established the first registration study of IgA Nephropathy in Children in China-"Registry of IgA Nephropathy in Chinese Children, RACC; ClinicalTrials.gov registration number is NCT03015974), and established a network database/registration system (www.igaregister.com), a biological specimen bank (including blood, urine, DNA and kidney tissue specimens); In this process, we deeply feel the importance and particularity of clinical research. It is very necessary for clinicians to understand and pay attention to the essence, laws and common misunderstandings of clinical research, and update the existing solidification concepts. Only in this way can we carry out high-quality clinical research, obtain truly valuable research results, and ultimately benefit patients.

Premature infants often need respiratory support when they have respiratory distress or respiratory failure due to immature lung development or various diseases; Respiratory support methods include non-invasive ventilation and invasive ventilation. Invasive respiratory support significantly reduces the mortality rate of respiratory failure in premature infants, but the complications such as ventilator-related lung injury and infection that it brings seriously affect the long-term prognosis of these premature infants, especially very premature infants^[1]。 In order to minimize the complications of invasive mechanical ventilation and effectively treat respiratory failure, in recent years, clinicians tend to give priority to non-invasive ventilation in the early stage, and decide whether to give invasive mechanical ventilation according to the supporting effect of non-invasive ventilation. At present, there are five types of non-invasive ventilation modes widely used in neonatal intensive care unit (NICU): nasal continuous positive airway pressure (NCPAP), noninvasive intermittent positive pressure ventilation (NIPPV), bi-level positive airway pressure (BiPAP), heated humidified high-flow nasal cannula (HHHFNC or HFNC), noninvasive high-frequency oscillatory ventilation (NHFOV). In order to standardize the clinical use of non-invasive ventilation support technology and achieve better therapeutic effect, based on the relevant theories and clinical experience of non-invasive ventilation for premature infants at home and abroad, and through the collective discussion of the 17th Neonatology Group of Pediatrics Branch of Chinese Medical Association, the clinical application suggestions of non-invasive respiratory support for premature infants were formulated for the reference of neonatal clinicians.

Primary immunodeficiency disease (PID) is a class of immune cell or immune molecule defects mainly caused by single gene mutations, resulting in reduced, absent or imbalanced immune regulatory function. The clinical manifestations are reduced anti-infective immune function of the body, and a group of diseases that are prone to tumors, autoimmune diseases, allergic diseases and inflammatory diseases. PID is a rare disease. There are many kinds of diseases but the incidence of individual diseases is very low. The pathogenesis and etiology of many diseases have not been fully elucidated. Therefore, the nomenclature and classification need to be constantly updated to facilitate the adoption of unified standards for research and academic exchange in various countries and regions. In 1970, the World Health Organization (WHO) organized a meeting in Geneva to classify and define PID for the first time. Since then, the International Federation of Immunological Societies (IUIS) PID expert group will hold meetings every 2 to 3 years to update the PID classification. The most recent expert meeting held in London in February 2017 gave the latest classification and elaboration of PID, and the full text was published in 2018 inJ Clin Immunol^[1]。 With the rapid application of high-throughput sequencing in clinical practice, the rapid progress of big data and bioinformatics, the detection rate of PID disease has obviously accelerated. In recent years, new genes and new diseases have been discovered and reported. In this latest classification, a total of 354 diseases are included, divided into 9 categories: (1) combined immunodeficiency diseases; (2) immunodeficiency syndrome with typical symptoms; (3) antibody immunodeficiency disease; (4) Immune disorders; (5) phagocytic cell defect; (6) natural immunodeficiency; (7) autoinflammatory diseases; (8) complement deficiency; (9) Phenomimetry of immune birth defects. This classification helps clinicians to understand and remember the clinical features of PID.

The 8-year-old male was admitted to the Department of Pediatrics of Puyang Oilfield General Hospital affiliated to Xinxiang Medical College due to the complaint of "pale complexion found for 5 days" and the proposed diagnosis of "severe anemia remains to be investigated". The child developed fever, cough and pale complexion after catching a cold 5 days before admission. He was diagnosed as "acute upper respiratory tract infection" in the outpatient department of our hospital. He was given oral drug treatment, but his condition did not improve. He was admitted after follow-up visit. The child was the second child of the mother, the second birth, and was born naturally at full term. He had a birth weight of 3.2 kg and a length of 52 cm. He had no history of asphyxia. He was in normal health and occasionally suffered from respiratory tract infection. After the child entered daycare at the age of 4, the parents found that he drank more water, urinated more, had slow weight and height growth in the past 2 years, had bedwetting at night 4 months before the onset of the disease, and drank less water 1 month before the doctor, but did not pay attention to it. No previous urine test, blood routine, liver and kidney function and abdominal ultrasound examination were performed.

An 11-year-old child was admitted to Guangzhou Children's Hospital because she was "diagnosed with chronic renal failure for more than 1 year and planned to undergo allogeneic kidney transplantation". More than a year ago, he was diagnosed with "C3 nephropathy and chronic renal failure". After that, he had regular hemodialysis for 1 year, and is now admitted to the hospital with "proposed kidney transplantation".

Case 1 female, 1 year old, was seen in Beijing Children's Hospital in October 2013 mainly because of "lagging development of great motor and unstable vertical head". The child was the first birth of the mother, born by cesarean section at term, with a birth weight of 3 300 g. After birth, it was found that crying and laughing were expressionless, the eyelids were incompletely closed, and both eyes were esotropic. Still unstable at the age of 1, unable to turn over and sit alone. Physical examination: head circumference 45 cm, masked face, epicanthal folds, both eyes oblique, abduction of the eyeball. Syndactyly of 2 to 5 fingers and oligosegmental deformity of 2 to 4 fingers of the right hand (Figure 1）。 The right chest wall is depressed and the pectoral muscles are not palpable (Figure 1）。 Hypotonia of the extremities. The clinical diagnosis is Poland-Mobius syndrome, and it is recommended to return home to strengthen nutrition and appropriate rehabilitation training. The child walked alone at the age of 2 years and 3 months, with widened step base and poor articulation. The Gesell test at the age of 2 years and 3 months showed 63 scores in adaptability, 65 scores in major motor, 59 scores in fine motor, 72 scores in language ability, 73 scores in personal-social ability, and 65 scores in average. At the time of follow-up visit, he was 5 years old and attended kindergarten. His cognition was roughly normal, and his mask face and esotropia in both eyes did not improve.

A 4-year-old girl was admitted to Hunan Provincial People's Hospital in March 2017 due to "intermittent right upper abdominal pain for 3 months, aggravated and fever for 15 days". During the course of the disease, it improved slightly after anti-infective treatment in the local hospital. After abdominal B-ultrasound in another hospital, it was suspected that exophytic hepatoblastoma was possible. In the past, there was a delayed healing of cards, and there was no repeated suppuration at the vaccination site, but it gradually healed nearly six months after vaccination. Toe and finger keratosis began to appear at the age of 6 months, and there were subcutaneous boils of the head, abdomen and buttocks at the age of 1 year (Figure 1）。 Has a history of urticaria, no history of repeated pneumonia, and normal growth and mental development. His parents are not close relatives, and there is no similar medical history in the family.

Primary nephrotic syndrome is a common glomerular disease in children. According to the efficacy of children on glucocorticoids, it is divided into steroid-sensitive nephrotic syndrome and steroid-resistant nephrotic syndrome (SRNS)^[1]。 The prognosis of SRNS is poor, with 30% to 50% of children progressing to end stage renal disease (ESRD) gradually within 10 years^[1]。 In recent years, it has been found that the mutations of nucleoporins (Nups) genes NUP107, NUP93 and NUP205 can lead to SRNS^[2,3,4,5,6]。 The clinicopathological characteristics of nephrotic syndrome (NS) caused by nucleoporin gene variation, the nucleoporin gene and its function, the analysis of nucleoporin gene variation, the pathogenesis of NS caused by nucleoporin gene variation and the significance of nucleoporin gene variation analysis are briefly described.

juvenile myelomonocytic leukemia (JMML) is a rare malignant hematological disease in children. It is a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) in children. As an invasive disease, it is characterized by excessive proliferation of mononuclear cells causing infiltration of spleen, liver, gastrointestinal tract and lung organs. The clinical manifestations are mainly anemia, hepatosplenic and lymph node enlargement. JMML has the characteristics of MDS and MPN at the same time, with large clinical heterogeneity and poor prognosis. It mainly involves infants and young children under 2 years old. The annual incidence rate is 1.2/1 million, accounting for 2% ~3% of childhood leukemia, and the male-female ratio is (1.4~2.5): 1^[1]。 The research progress on the pathogenesis of JMML is reviewed.

extracorporeal cardiopulmonary resuscitation (ECPR) is a rapid implementation of extracorporeal membrane oxygenation (ECMO) technology for patients who cannot restore spontaneous heart rhythm through conventional cardiopulmonary resuscitation (CCPR) or who cannot maintain spontaneous heart rhythm through repeated cardiac arrest, to temporarily replace cardiopulmonary function, ensure effective blood perfusion and sufficient oxygen supply to organs, and increase the possibility of restoration of spontaneous circulation (ROSC). Domestic children's ECPR started late, and there is a lack of mature experience in the indications, timing and management of ECPR establishment after transfer. This is reviewed for reference.

status epilepticus (SE) is a central nervous system disorder characterized by persistent or frequent seizures with intermittent disturbance of consciousness, often causing serious sequelae or death. 2015 International Alliance Against Epilepsy (ILAE) updated SE definition^[1]: a pathological condition in which a mechanism of inhibition of brain attacks is impaired, or a new mechanism of epileptogenicity (time point t1) is initiated; It is also an abnormality that can lead to long-term adverse outcomes (time point t2), including neuronal death, damage, and network alterations, depending on the type and duration of the episode. This concept includes two operational elements: one is the onset time limit and time point (t1), beyond which the onset should be considered as sustained onset activity; The second refers to the episode sustained activity time point (t2) that causes the risk of long-term brain injury. Both time points of convulsive (tonic-clonic) SE (t1=5 min and t2=30 min) are based on animal experiments and clinical studies, and these time points should be the most desirable and practical values for evaluation or judgment at present. With the gradual deepening of the research on pathophysiology, treatment opportunity, efficacy and prognosis of SE, the new definition emphasizes the symptomatology, etiology, EEG data and age characteristics of SE.

Twenty-five years after the recommendations for the diagnosis and treatment of acute lymphoblastic leukemia in China were first published, from April 26 to 28, 2018, the National Forum on Pediatric Hematology and Oncology was held again in the beautiful coastal city of Beihai. This forum was jointly organized by the Journal of Chinese Medical Association, the Editorial Committee of Chinese Journal of Pediatrics, the Hematology Group of Pediatrics Branch of Chinese Medical Association, and the Pediatric Hematology and Oncology Group of Chinese Medical Doctors Association. At 8: 00 a.m. on April 27th, Professor Wang Tianyou, the designated chairman of Pediatrics Branch of Chinese Medical Association and head of Hematology Group of Pediatrics Branch of Chinese Medical Association, delivered the opening speech. Professor Chen Yongbin, Party Secretary of the First Affiliated Hospital of Guangxi Medical University, the host, made a warm welcome speech. A total of 517 papers were received in this conference, with wide content and high quality. Participants from all over the country presented their clinical research achievements in 49 conference speeches and 69 posters. Fifteen experts gave wonderful special lectures on the latest progress, achievements and advanced experience in their respective fields. The highlights of this forum are now summarized:

The 5th International Conference on Nutrition and Growth (5th International Conference on Nutrition and Growth) was held in Paris, France from March 1 to 3, 2018. Nearly 800 delegates from more than 20 countries attended the Conference, including experts in pediatric medicine, clinical Nutrition, neonatology, child health care and other fields. The schedule of the meetings was tight, with different topics divided into four plenary sessions, seven chapters, eight oral presentations and nine satellite sessions. The broad spectrum of child nutrition and growth is also evident at this international conference: nutrition of premature infants, newborns, infants and young children, as well as children and adolescents in different age groups; Breast milk, formula, intestinal microorganisms or prebiotics or probiotics, special foods and health; Effects of environmental factors on growth and health, nutrition and cognition, lifestyle and childhood obesity, etc. However, the mainstream and core content throughout the Conference is the study of breastfeeding and the composition of breast milk, and the Conference will be briefed on this aspect.

One of the important methods to transform clinical research into clinical application is to establish predictive models. This kind of articles has become a popular type in recent years. However, the models in this article are rarely used in clinical practice. One of the main reasons is that the effectiveness of the models is not evaluated completely, and the effectiveness of the models in practice is not good. The efficacy evaluation of the predictive model includes discrimination ability, accuracy and clinical utility. The discrimination ability of the predictive model is the discrimination ability, which is mainly evaluated by the subject operating characteristic curve (ROC curve). The ROC curve is a curve divided into two categories according to a series of different thresholds, drawn with the true positive rate (sensitivity) as the ordinate and the false positive rate (1-specificity) as the abscissa. The ROC curve combines sensitivity and specificity by graphical method, which can accurately reflect the relationship between specificity and sensitivity of model prediction values. The closer the ROC curve is to the upper left corner, the larger the area under the curve, indicating that its prediction value is greater. At the same time, it can be used for comparison between different indexes. It is generally believed that the diagnostic value is greater when the area under the curve is greater than 0.8, and the specific predictive value needs to be combined with clinical practice.

Professor Sun Meiyue, former deputy editor-in-chief of the editorial board of Chinese Journal of Pediatrics, member of the emergency group of Pediatrics Branch of Chinese Medical Association, a famous pediatric expert in China, and Professor Sun Meiyue of Children's Hospital affiliated to Zhejiang University School of Medicine, died in Hangzhou at the age of 81 at 3: 05 on July 26, 2018.